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1.
BMC Cancer ; 22(1): 255, 2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35264135

RESUMEN

BACKGROUND: As part of the multi-country I-O Optimise research initiative, this population-based study evaluated real-world treatment patterns and overall survival (OS) in patients treated for advanced non-small cell lung cancer (NSCLC) before and after public reimbursement of immuno-oncology (I-O) therapies in Alberta province, Canada. METHODS: This study used data from the Oncology Outcomes (O2) database, which holds information for ~ 4.5 million residents of Alberta. Eligible patients were adults newly diagnosed with NSCLC between January 2010 and December 2017 and receiving first-line therapy for advanced NSCLC (stage IIIB or IV) either in January 2010-March 2016 (pre-I-O period) or April 2016-June 2019 (post-I-O period). Time periods were based on the first public reimbursement of I-O therapy in Alberta (April 2017), with a built-in 1-year lag time before this date to allow progression to second-line therapy, for which the I-O therapy was indicated. Kaplan-Meier methods were used to estimate OS. RESULTS: Of 2244 analyzed patients, 1501 (66.9%) and 743 (33.1%) received first-line treatment in the pre-I-O and post-I-O periods, respectively. Between the pre-I-O and post-I-O periods, proportions of patients receiving chemotherapy decreased, with parallel increases in proportions receiving I-O therapies in both the first-line (from < 0.5% to 17%) and second-line (from 8% to 47%) settings. Increased use of I-O therapies in the post-I-O period was observed in subgroups with non-squamous (first line, 15%; second line, 39%) and squamous (first line, 25%; second line, 65%) histology. First-line use of tyrosine kinase inhibitors also increased among patients with non-squamous histology (from 26% to 30%). In parallel with these evolving treatment patterns, median OS increased from 10.2 to 12.1 months for all patients (P < 0.001), from 11.8 to 13.7 months for patients with non-squamous histology (P = 0.022) and from 7.8 to 9.4 months for patients with squamous histology (P = 0.215). CONCLUSIONS: Following public reimbursement, there was a rapid and profound adoption of I-O therapies for advanced NSCLC in Alberta, Canada. In addition, OS outcomes were significantly improved for patients treated in the post-I-O versus pre-I-O periods. These data lend support to the emerging body of evidence for the potential real-world benefits of I-O therapies for treatment of patients with advanced NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunoterapia/tendencias , Reembolso de Seguro de Salud/tendencias , Neoplasias Pulmonares/terapia , Oncología Médica/tendencias , Pautas de la Práctica en Medicina/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Alberta , Carcinoma de Pulmón de Células no Pequeñas/economía , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Inmunoterapia/economía , Neoplasias Pulmonares/economía , Neoplasias Pulmonares/mortalidad , Masculino , Oncología Médica/economía , Persona de Mediana Edad , Pautas de la Práctica en Medicina/economía
2.
Dis Markers ; 2022: 5296830, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35256890

RESUMEN

While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Biología Computacional , Medicamentos Herbarios Chinos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Línea Celular Tumoral , Interacciones Farmacológicas , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Simulación del Acoplamiento Molecular , Pronóstico , Análisis de Supervivencia
3.
Dis Markers ; 2022: 5118444, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35237359

RESUMEN

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Epigénesis Genética , Neoplasias Pulmonares , Pronóstico , ARN Largo no Codificante/genética , Tasa de Supervivencia , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Femenino , Perfilación de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Reproducibilidad de los Resultados
4.
PLoS One ; 17(2): e0261767, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35108265

RESUMEN

BACKGROUND: Retrospective data demonstrates that robotic-assisted thoracoscopic surgery provides many benefits, such as decreased postoperative pain, lower mortality, shorter length of stay, shorter chest tube duration, and reductions in the incidence of common postoperative pulmonary complications, when compared to video-assisted thoracoscopic surgery. Despite the potential benefits of robotic surgery, there are two major barriers against its widespread adoption in thoracic surgery: lack of high-quality prospective data, and the perceived higher cost of it. Therefore, in the face of these barriers, a prospective randomized controlled trial comparing robotic- to video-assisted thoracoscopic surgery is needed. The RAVAL trial is a two-phase, international, multi-centered, blinded, parallel, randomized controlled trial that is comparing robotic- to video-assisted lobectomy for early-stage non-small cell lung cancer that has been enrolling patients since 2016. METHODS: The RAVAL trial will be conducted in two phases: Phase A will enroll 186 early-stage non-small cell lung cancer patients who are candidates for minimally invasive pulmonary lobectomy; while Phase B will continue to recruit until 592 patients are enrolled. After consent, participants will be randomized in a 1:1 ratio to either robotic- or video-assisted lobectomy, and blinded to the type of surgery they are allocated to. Health-related quality of life questionnaires will be administered at baseline, postoperative day 1, weeks 3, 7, 12, months 6, 12, 18, 24, and years 3, 4, 5. The primary objective of the RAVAL trial is to determine the difference in patient-reported health-related quality of life outcomes between the robotic- and video-assisted lobectomy groups at 12 weeks. Secondary objectives include determining the differences in cost-effectiveness, and in the 5-year survival data between the two arms. The results of the primary objective will be reported once Phase A has completed accrual and the 12-month follow-ups are completed. The results of the secondary objectives will be reported once Phase B has completed accrual and the 5-year follow-ups are completed. DISCUSSION: If successfully completed, the RAVAL Trial will have studied patient-reported outcomes, cost-effectiveness, and survival of robotic- versus video-assisted lobectomy in a prospective, randomized, blinded fashion in an international setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02617186. Registered 22-September-2015. https://clinicaltrials.gov/ct2/show/NCT02617186.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Cirugía Asistida por Video/métodos , Adulto , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Análisis Costo-Beneficio , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Posoperatorio , Calidad de Vida , Método Simple Ciego , Tasa de Supervivencia , Toracotomía
5.
J Clin Psychiatry ; 83(2)2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-35192749

RESUMEN

Mental health clinicians often hear seriously ill patients ask the unanswerable: Why did this happen? What is the meaning of my suffering? In the inpatient setting, general medical ward, or oncology unit, patients are confronted with their mortality in new, urgent ways. Palliative medicine, or the specialized, comprehensive care of patients facing a life-limiting illness, occupies a unique and liminal space. Although often practiced by clinicians with non-mental health training backgrounds, there exists ample psychological content to be explored in the palliative care encounter. In this article, we present the case of a husband and international businessperson who experienced terminal complications from an advanced stage lung cancer. His illness was not responsive to multiple cancer-directed treatments, and he developed respiratory failure requiring high levels of supplemental oxygen support, from which he was unable to wean. Palliative care consultation was sought with the multiple objectives of ameliorating his severe death anxiety and persistent dyspnea as well as assisting in the clarification of his end-of-life wishes. Our goal with this case presentation and related discussion is to introduce the psychological aspects of palliative medicine to psychiatrists and psychotherapists.


Asunto(s)
Muerte , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/psicología , Cuidados Paliativos , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/psicología , Humanos , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/terapia , Masculino , Servicios de Salud Mental/normas , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Derivación y Consulta , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia
6.
Cancer Cell ; 40(3): 240-243, 2022 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35216677

RESUMEN

In this issue of Cancer Cell, Patil et al. report that increased plasma cell signatures are predictive of an extended overall survival in non-small-cell lung cancer patients treated with a PD-L1 inhibitor and that these cells are associated with the presence of tertiary lymphoid structures.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Células Plasmáticas
7.
Life Sci ; 296: 120408, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35202641

RESUMEN

AIMS: The adenosine-to-inosine (A-to-I) RNA editing controlled by the editing genes are known to diversify transcripts in human. Aberrant A-to-I editing due to dysregulation of the editing genes are involved in cancer development. However, it is still largely unclear how single nucleotide polymorphisms (SNPs) in the A-to-I editing genes confer to recurrence and/or drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: In this study, we systematically evaluated and validated the role of twenty-eight potential functional genetic variants in four A-to-I editing genes (ADAR, ADARB1, ADARB2 and AIMP2) in prognosis of NSCLC patients receiving EGFR-TKIs. KEY FINDINGS: We identified the ADAR rs1127309, rs1127317, and rs2229857 SNPs markedly contributing to prognosis of patients treated with EGFR-TKIs. Interestingly, SNP rs1127317 locating in the ADAR 3'-untranslated region regulates gene expression in an allele-specific manner via modulating binding of miR-454-5p in cells. In support of this, patients with the rs1127317 C allele correlated with elevated ADAR expression in tumors showed profoundly shorten survival after EGFR-TKIs therapy compared to the A allele carriers. Silencing of ADAR notably enhanced gefitinib sensitivities of NSCLC cells. SIGNIFICANCE: Our findings highlight the importance of the A-to-I RNA editing in drug resistance and nominate ADAR as a potential therapeutic target for unresectable NSCLC.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Adenosina Desaminasa/genética , Antineoplásicos/farmacología , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Unión al ARN/genética , Regiones no Traducidas 3' , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Gefitinib/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple
8.
Medicine (Baltimore) ; 101(6): e28814, 2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35147120

RESUMEN

ABSTRACT: Lung cancer remains the worldwide leading cause of cancer-related death. Currently, prognostic biomarkers for the detection and stratification of lung cancer are being investigated for clinical use. The surface protein cluster of differentiation 49b (CD49b) plays an important role in promoting cell proliferation and invasion in different tumor entities and blocking CD49b improved the tumor immune response. Overexpression of CD49b has been associated with unfavorable survival rates in several malignant tumor entities, such as prostate cancer, gastric cancer and colon cancer. Therefore, we aimed to analyze the protein expression of CD49b in patients with different types of lung cancer and additionally to identify the influence of CD49b on clinicopathological characteristics and overall survival.Expression levels of CD49b were retrospective analyzed by immunohistochemistry in 92 cases of pulmonary adenocarcinoma (AC), 85 cases of squamous cell lung carcinoma (SQCLC) and 32 cases of small cell lung cancer (SCLC) and correlated with clinicopathological characteristics and patients' overall survival.A strong expression of CD49b was most seen in SQCLC (78%), followed by AC (48%) and SCLC (9%). All patients combined, strong expression of CD49b correlated significantly with poorer overall survival. However, an increased expression of CD49b correlated significantly with a poorer survival rate only in SQCLC. In AC and SCLC, no significant correlation could be demonstrated in this regard.In our study, CD49b expression was associated with poor overall survival in patients with SQCLC. Accordingly, CD49b could serve as a new prognostic biomarker and, moreover, be a potential new drug target in SQCLC.


Asunto(s)
Adenocarcinoma del Pulmón/metabolismo , Carcinoma de Células Escamosas/metabolismo , Integrina alfa2/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Diferenciación Celular , Femenino , Humanos , Integrina alfa2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Tasa de Supervivencia
9.
BMC Cancer ; 22(1): 188, 2022 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-35183135

RESUMEN

BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD). METHODS: Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001). CONCLUSIONS: This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Factores de Transcripción Forkhead/genética , Redes Reguladoras de Genes/genética , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/genética , Humanos , Neoplasias Pulmonares/mortalidad , MicroARNs/genética , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/genética
10.
BMC Cancer ; 22(1): 204, 2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35197014

RESUMEN

BACKGROUND: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at the Uganda Cancer Institute (UCI). METHODS: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. RESULTS: Of the 207 patients enrolled, 56.5% (n = 117) were female, median age was 60 years (range: 20-94), 78.7% (n = 163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n = 48). Majority had non-small cell lung cancer (96.6%, n = 200) with 74.5% (n = 149) adenocarcinoma and 19% (n = 38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n = 199) in stage IV. Chemotherapy (44.9%, n = 93) and biological therapy (34.8%, n = 72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7, 29.7, 11.8, and 1.7%, respectively. The median survival time of 4.4 months was not statistically significantly different between participants with NSCLC or SCLC (4.5 versus 3.9 months, p = .335). CONCLUSION: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer and patients are predominantly females, and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early detection and improve outcomes.


Asunto(s)
Adenocarcinoma/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Uganda/epidemiología , Adulto Joven
11.
Med Sci Monit ; 28: e934050, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35102130

RESUMEN

BACKGROUND Lung adenocarcinoma (LUAD) is the predominant histological type of lung cancer with high morbidity and mortality. Ferroptosis is regarded as a new pattern of programmed cell death concerned with the progression of lung cancer characterized by lipid peroxidation. Nevertheless, the prognostic role of ferroptosis-related genes for LUAD warrant to be explored. MATERIAL AND METHODS RNA sequencing and relevant clinical patient data were obtained from public-access databanks. A prognostic model was constructed through the LASSO Cox regression in the cancer genome atlas cohort. The diagnostic value of the prognostic model was further evaluated in the gene expression omnibus cohort. RESULTS Most of the ferroptosis-related genes (69.9%) were differentially expressed between tumor and adjacent non-cancerous tissues. 43 differentially expressed genes showed a close association with the prognosis of LUAD patients (adjusted p-value <0.05). An 18-gene signature was built and applied to assign patients into high vs low-risk groups. Compared with the high-risk group, patients defined as the low-risk group suffered significantly prolonged OS. Both uni- and multivariate analyses demonstrated that the signature-based score served as a crucial role in influencing the OS of LUAD patients (hazard ratio >1, p<0.001). The immunity-related signaling pathway was enriched in the functional analysis and the infiltration of the immune cells showed a great difference between groups. CONCLUSIONS The predictive model could be applied for prognostic prediction for LUAD. Targeting ferroptosis could be a possible curative strategy against LUAD, and immunomodulation may be one of the potential mechanisms.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/genética , Ferroptosis/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Estudios de Cohortes , Humanos , Análisis de Secuencia de ARN/métodos , Análisis de Supervivencia
12.
Radiat Oncol ; 17(1): 26, 2022 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-35123531

RESUMEN

BACKGROUND: In the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI. METHODS: Data from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI. RESULTS: Of 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up. CONCLUSIONS: In the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI.


Asunto(s)
Neoplasias Encefálicas/prevención & control , Irradiación Craneana , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Imagen por Resonancia Magnética , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/secundario , Tasa de Supervivencia
13.
Radiat Oncol ; 17(1): 29, 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-35139856

RESUMEN

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous disease and treatment burden. Advances in imaging modality show promising results for radiotherapy planning. In this multicentric study, we evaluated the impact of PET/CT-based radiotherapy planning on the prognosis of patients with stage III NSCLC. METHOD AND PATIENTS: A retrospective observational cohort study (ARO 2017-01/NCT03055715) was conducted by the young DEGRO trial group of the German Society for Radiation Oncology (DEGRO) with the primary objective to assess the effect of tumour volume change during chemoradiotherapy and the secondary objective to assess the effect of treatment planning on survival. Three hundred forty-seven patients with stage III NSCLC treated at 21 university centers between January 2010 and December 2013 were enrolled in this trial. Patients received primary curative chemoradiotherapy with an intended dose of 50 Gy (hypofractionated) or > 60 Gy (normofractionated). To assess the effect of radiotherapy planning modality on overall survival, we used multivariate frailty models. Models were adjusted for gross tumor volume at the initiation of therapy, age, sex, simultaneous chemotherapy, lung comorbidities, RT dose and tumor grade. By considering the random effect, we can account for heterogeneity in survival and considered covariates within the model in relation to the study side. RESULTS: Patients were predominantly male (n = 269, 78.4%) with mainly adenocarcinoma (56.4%) and an average of 67.2 years. Adaptation of radiotherapy with consecutive reduction of irradiation volume showed no significant disadvantage for patient survival (HR = 1.21, 95% CI 0.89-1.64). The use of PET/CT co-registration in radiation planning tended to result in better oncologic outcomes, although no significant association could be shown (HR = 0.8, 95% CI 0.56-1.16). Centers with a consistent planning strategy performed better than those without a preferred planning method (0.62, 95% CI 0.41-0.94). CONCLUSION: A consistent planning strategy has positive effects on overall survival. The use of PET/CT-based adaptive radiotherapy planning shows a similar survival prospect with the prospective of lower treatment volumes. In future research, toxicities need to be analysed in order to assess such reasoning.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioterapia Guiada por Imagen , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
14.
Sci Rep ; 12(1): 1976, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35132098

RESUMEN

Lung cancer is one of the most common malignancy worldwide and causes estimated 1.6 million deaths each year. Cancer immunosurveillance has been found to play an important role in lung cancer and may be related with its prognosis. KLRK1, encoding NKG2D, is a homodimeric lectin-like receptor. However, there has not been one research of KLRK1 as a biomarker in lung cancer. Data including patients` clinical characteristics and RNAseq information of KLRK1 from TCGA were downloaded. A total of 1019 patients with lung cancer were included in this study, among which 407 patients were female and 611 patients were male. Evaluations of mRNA expression, diagnostic value by ROC (receiver operating characteristic) curves and prognostic value by survival curve, Cox model and subgroup analysis were performed. The level of KLRK1 expression in lung adenocarcinoma cancer tissues and normal lung tissues was detected by qRT-PCR. The CCK-8 assay investigated the proliferation rate and the wound healing assay assessed the migratory ability in vitro. The expression of KLRK1 in tumor was lower than that in normal tissue. KLRK1 expression was associated with gender, histologic grade, stage, T classification and vital status. Patients with high KLRK1 expression presented an improved overall survival (P = 0.0036) and relapse free survival (P = 0.0031). KLRK1 was found to have significant prognostic value in lung adenocarcinoma (P = 0.015), stage I/II (P = 0.03), older patients (P = 0.0052), and male (P = 0.0047) by subgroup overall survival analysis, and in lung adenocarcinoma (P = 0.0094), stage I/II (P = 0.0076), older patients (P = 0.0072), and male (P = 0.0033) by subgroup relapse free survival analysis. Lung adenocarcinoma cancer patients with high KLRK1 expression presented an improved overall survival (P = 0.015) and relapse free survival (P = 0.0094). In vitro studies indicated that KLRK1 inhibited tumor cell proliferation and migration. KLRK1 was an independent prognostic factor and high KLRK1 expression indicated a better overall and relapse free survival. KLRK1 may be a prognostic biomarker for lung adenocarcinoma cancer.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Células A549 , Adenocarcinoma/mortalidad , Biomarcadores de Tumor/genética , Movimiento Celular/genética , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Curva ROC
15.
Biochem Biophys Res Commun ; 598: 1-8, 2022 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-35149432

RESUMEN

BACKGROUND: ADAMTS8 expression has been identified to be low in many cancers including lung cancer. However, the specific functions and regulatory system of ADAMTS8 remain to be unveiled. PURPOSE: To study the potential modulatory mechanism of ADAMTS8 in lung cancer in cell and xenograft mice models. METHODS: Differential expression of ADAMTS8 in lung cancer was analyzed on online tools. So was the overall survival curve in association with ADAMTS8/VEGFA expression in lung cancer patients. RT-qPCR was applied to validate the ADAMTS8 expression in lung cancer cell lines H460 and A549, with the normal lung epithelial cell Beas-2b as a control. Thereafter, overexpressed and knockdown plasmids were constructed for transfection. Colony and flow cytometry methods were used for cell proliferation and apoptosis. RT-qPCR and Western blot methods validated the changes in VEGFA after ADAMTS8 regulation in cells. Tube formation and Transwell methods were applied to observe the changes in tube formation and migration in HUVECs induced by tumor conditioned medium (TCM). Stable-transfected cells were injected subcutaneously into nude mice. H&E and Immunohistochemistry were applied to analyze the pathological differences and protein changes of ADAMTS8, VEGFA and CD31. RESULTS: High ADAMTS8 was correlated with high overall survival rate in lung cancer patients. ADAMTS8 was also abnormally downregulated in NSCLC cells. Upregulation of ADAMTS8 suppressed cell proliferation and enhanced apoptosis while downregulation of ADAMTS8 promoted cell proliferation and decreased apoptosis. VEGFA was negatively correlated with ADAMTS8 in lung cancer tissues. Upregulation of ADAMTS8 inhibited VEGFA in mRNA and protein levels. Further, knockdown of ADAMTS8 induced tube formation and migration of HUVECs and upregulation of ADAMTS8 inhibited this. In addition, upregulation of ADAMTS8 in nude mice inhibited tumor growth and also suppressed VEGFA and CD31 in tumors. CONCLUSION: ADAMTS8 inhibited lung cancer progression through suppressing VEGFA in lung cancer.


Asunto(s)
Proteínas ADAMTS/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Factor A de Crecimiento Endotelial Vascular/genética , Proteínas ADAMTS/metabolismo , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Pulmonares/genética , Ratones Endogámicos BALB C , Neovascularización Patológica/genética , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Asian Pac J Cancer Prev ; 23(2): 435-443, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35225454

RESUMEN

OBJECTIVES: Lung cancer continues to be  the leading cause of cancer-related deathworldwide. Have been reported high mortality rates from lung cancer in Latin America, but the disparities within the regions of Peru and under-reporting death certification reported prevent the inclusion of Peru in analysis of the mortality trends for lung cancer. We evaluated lung cancer mortality trends and smoking prevalence in Peru and its geographical areas. MATERIALS AND METHODS: We obtained the data from the registry of the Peruvian Ministry of Health between 2008 and 2017. Mortality rates per 100,000 person-years were computed using the world's SEGI population and trends were analyzed using the Joinpoint regression Program Version 4.7.0. Smoking prevalence was estimated from the Demographic and Family Health Survey. RESULTS: In Peru, mortality rates were roughly 1.3 times higher in males than in females. The coast region had significant downward trends among males, whereas the highlands region had significant upward trends among females. According to provinces, Apurimac showed an annually significant rise in both sexes (+10.6% in males, and +11.6% in females). In general, smoking prevalence was higher in males compared to females, principally among young adults.   Conclusions: Peru showed downward mortality trends in the last decade with variability across regions. Males had a higher smoking prevalence, principally among young adults. Public health interventions for smoking reduction should be implemented to reduce lung cancer mortality.


Asunto(s)
Neoplasias Pulmonares/mortalidad , Mortalidad/tendencias , Fumar/epidemiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perú , Prevalencia , Sistema de Registros
17.
Sci Rep ; 12(1): 1705, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35105934

RESUMEN

NEKs are proteins that are involved in various cell processes and play important roles in the formation and development of cancer. However, few studies have examined the role of NEKs in the development of non-small-cell lung carcinoma (NSCLC). To address this problem, the Oncomine, UALCAN, and the Human Protein Atlas databases were used to analyze differential NEK expression and its clinicopathological parameters, while the Kaplan-Meier, cBioPortal, GEPIA, and DAVID databases were used to analyze survival, gene mutations, similar genes, and biological enrichments. The rate of NEK family gene mutation was high (> 50%) in patients with NSCLC, in which NEK2/4/6/8/ was overexpressed and significantly correlated with tumor stage and nodal metastasis status. In addition, the high expression of NEK2/3mRNA was significantly associated with poor prognosis in patients with NSCLC, while high expression of NEK1/4/6/7/8/9/10/11mRNA was associated with good prognosis. In summary, these results suggest that NEK2/4/6/8 may be a potential prognostic biomarker for the survival of patients with NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Quinasas Relacionadas con NIMA/genética , Proteómica/métodos , Transcriptoma/genética , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Bases de Datos de Proteínas , Humanos , Estimación de Kaplan-Meier , Mutación , Pronóstico , ARN Mensajero/genética , Tasa de Supervivencia
18.
PLoS One ; 17(2): e0263247, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35130287

RESUMEN

A recent study suggested that proton pump inhibitor (PPI) use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) was associated with poor clinical outcomes. However, the clinical impact of PPI use on the outcome of patients receiving ICIs for postoperative recurrent NSCLC is unknown. The outcomes of 95 patients with postoperative recurrence of NSCLC receiving ICIs at 3 medical centers in Japan were analyzed. We conducted adjusted Kaplan-Meier survival analyses with the log-rank test, a Cox proportional hazards regression analysis, and a logistic regression analysis using inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan-Meier curves revealed that the progression-free survival (PFS), but not the overall survival (OS), was significantly longer in patients who did not receive PPIs than in those who did receive them. The IPTW-adjusted Cox regression analysis revealed that PPI use was an independent poor prognostic factor for the PFS and OS. Furthermore, in the IPTW-adjusted logistic regression analysis, PPI non-use was an independent predictor of disease control. In this multicenter and retrospective study, PPI use was associated with poor clinical outcomes in patients with postoperative recurrence of NSCLC who were receiving ICIs. PPIs should not be prescribed indiscriminately to patients with postoperative recurrence of NSCLC who intend to receive ICIs. These findings should be validated in a future prospective study.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de la Bomba de Protones/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Estudios Transversales , Quimioterapia Combinada , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Japón/epidemiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Complicaciones Posoperatorias/tratamiento farmacológico , Periodo Posoperatorio , Inhibidores de la Bomba de Protones/efectos adversos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
19.
JAMA Netw Open ; 5(2): e220130, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35188551

RESUMEN

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19-related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed.


Asunto(s)
COVID-19/complicaciones , Neoplasias Hematológicas/mortalidad , Neoplasias Pulmonares/mortalidad , SARS-CoV-2 , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Quimioterapia , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Humanos , Inmunoterapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Reino Unido
20.
J Immunother Cancer ; 10(2)2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35190375

RESUMEN

BACKGROUND: The efficacy of atezolizumab (A) and/or bevacizumab (B) with carboplatin/paclitaxel (CP) chemotherapy was explored in the phase III, randomized IMpower150 study in patients with non-squamous non-small cell lung cancer (NSCLC) according to KRAS mutations (mKRAS) and co-occurring STK11, KEAP1, or TP53 mutations. METHODS: Mutation status was determined by circulating tumor DNA next-generation sequencing. Overall survival (OS) and progression-free survival (PFS) were analyzed in a mutation-evaluable intention-to-treat population (MEP; n=920) and SP263 (programmed cell death ligand 1 (PD-L1)) biomarker-evaluable population (n=774). RESULTS: Within the mKRAS population (24.5% of MEP), ABCP showed numerical improvements vs BCP in median OS (19.8 vs 9.9 months; HR 0.50; 95% CI 0.34 to 0.72) and PFS (8.1 vs 5.8 months; HR 0.42; 95% CI 0.29 to 0.61)-greater than with ACP (OS: 11.7 vs 9.9 months; HR 0.63; 95% CI 0.43 to 0.91; PFS: 4.8 vs 5.8 months; HR 0.80; 95% CI 0.56 to 1.13) vs BCP. Across PD-L1 subgroups in mKRAS patients, OS and PFS were longer with ABCP vs BCP, but OS with ACP was similar to BCP in PD-L1-low and PD-L1-negative subgroups. Conversely, in KRAS-WT patients, OS was longer with ACP than with ABCP or BCP across PD-L1 subgroups. KRAS was frequently comutated with STK11, KEAP1, and TP53; these subgroups conferred different prognostic outcomes. Within the mKRAS population, STK11 and/or KEAP1 mutations were associated with inferior OS and PFS across treatments compared with STK11-WT and/or KEAP1-WT. In mKRAS patients with co-occurring mSTK11 and/or mKEAP1 (44.9%) or mTP53 (49.3%), survival was longer with ABCP than with ACP or BCP. CONCLUSIONS: These analyses support previous findings of mutation of STK11 and/or KEAP1 as poor prognostic indicators. While clinical efficacy favored ABCP and ACP vs BCP in these mutational subgroups, survival benefits were greater in the mKRAS and KEAP1-WT and STK11-WT population vs mKRAS and mKEAP1 and mSTK11 population, suggesting both prognostic and predictive effects. Overall, these results suggest that atezolizumab combined with bevacizumab and chemotherapy is an efficacious first-line treatment in metastatic NSCLC subgroups with mKRAS and co-occurring STK11 and/or KEAP1 or TP53 mutations and/or high PD-L1 expression.


Asunto(s)
/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anticuerpos Monoclonales Humanizados/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Bevacizumab/farmacología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Mutación , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos
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