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3.
Oncology ; 99(1): 32-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32894845

RESUMO

OBJECTIVES: The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced EGFR-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. METHODS: We enrolled advanced EGFR-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. RESULTS: A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, p < 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6-33.7] vs. 9.4 [95% CI 8.4-10.4] months; aHR 0.40 [95% CI 0.30-0.54], p < 0.001) and overall survival (56.8 [95% CI 36.3-77.2] vs. 31.8 [95% CI 28.2-35.4] months; aHR 0.57 [95% CI 0.39-0.84], p = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0--1/M1a-malignant pleural effusion disease in the non-resection group (n = 19) (p < 0.001 and p = 0.002, respectively). CONCLUSION: PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.


Assuntos
Adenocarcinoma de Pulmão/cirurgia , Recidiva Local de Neoplasia/cirurgia , Inibidores de Proteínas Quinases/administração & dosagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Intervalo Livre de Progressão , Resultado do Tratamento
4.
Life Sci ; 265: 118797, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33285162

RESUMO

AIMS: Lung cancer was the most fatal malignancy, dominated the cancer related mortality list for years, and we tried to distinguish the lung adenocarcinoma patients at higher risk from those bearing lower therapy resistance and recurrence risk. MATERIALS: Patients information from clinical Sequencing Cohorts and from the Regional Medical Center of the Middle-West China were included. The whole-exome sequencing was analyzed for risk evaluation. KEY FINDINGS: We found that Smoking stimulated the oncogenic genes mutations, and the most frequently mutated genes of EGFR, KRAS, and TP53 (E/K/P) were identified. Different N stage affected the survival prognosis of patients bearing E/K/P mutations, but the T stage and AJCC stage did not. Radiation failed to prolong survival of phase II/III patients who didn't receive surgery. In those received surgery, radiation also failed to prolong survival of phase II/III patients. Radiation did not improve the prognosis in patients bearing E/K/P mutation burdens, whose differences were identified in gender or smoking-history classified groups. SIGNIFICANCE: Smoking status and history contributed to oncogenic mutation burdens associated therapy resistance, and the aggressive treatment, especially to radiation, may lead to worse therapy response to current and past smoking behavior.


Assuntos
Adenocarcinoma de Pulmão/genética , Carcinogênese/genética , Neoplasias Pulmonares/genética , Mutação/genética , Oncogenes/genética , Fumar/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Oncogenes/efeitos dos fármacos , Fumar/patologia , Fumar/terapia , Taxa de Sobrevida/tendências , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(49): e23503, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285759

RESUMO

INTRODUCTION: Lung adenocarcinoma is the most common type of lung cancer. Distant metastasis of lung adenocarcinoma often occurs in multiple organs. The common metastasis sites of lung cancer include the lungs, brain, bones, adrenal glands, and lymph nodes; however, breast metastasis is rare. PATIENT CONCERNS: In this report, we describe a case of breast metastasis from lung adenocarcinoma. A 55-year-old woman reported left breast pain for more than 1 month. DIAGNOSIS: Based on imaging, pathological examination, and immunohistochemical examination, the diagnosis of breast metastasis from lung adenocarcinoma was confirmed. Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement were not detected by next-generation sequencing. INTERVENTIONS: The patient was treated with six courses of a combination of albumin-bound paclitaxel, cisplatin, and bevacizumab over 21 days. OUTCOMES: After six cycles of palliative chemotherapy, her left breast pain and swelling subsided; in addition, her serum CA12-5, CYFRA, and CEA levels normalized by April 2019. PR status was evaluated as per the RECIST 1.1 criteria. The patient developed brain metastases 3 months later and died due to multiple organ failure. CONCLUSION: The possibility of breast metastasis should be considered in patients with existing malignant tumors and breast pain. Clinical and imaging examinations are helpful for diagnosis, and pathological and immunohistochemical analyses are the most important diagnostic tools.


Assuntos
Adenocarcinoma de Pulmão/secundário , Neoplasias da Mama/secundário , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/patologia , Mama/patologia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade
6.
Isr Med Assoc J ; 22(12): 784-787, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33381953

RESUMO

BACKGROUND: Guidelines recommend testing for multiple biomarkers in non-small cell lung cancer (NSCLC) tumors. Blood-based liquid biopsy analyzing cell-free DNA (cfDNA) could be used in addition to tumor biopsy genotyping, especially if tissue/time are limiting. OBJECTIVES: To investigate the clinical utility of early cfDNA analysis (Guardant360® CDx) in treatment-naïve NSCLC patients. METHODS: A prospective cohort of treatment-naïve patients with metastatic NSCLC who underwent tumor and cfDNA analysis between 12/2018 and 2/2019 were included. RESULTS: Ten patients were included: 6 males, median age 70.5 years (range 48-87), 8 prior smokers. Liquid biopsy was sent when cancer cells were detected in the biopsy specimen. Median time from diagnosis to receiving the report on the last biomarker from the tumor biopsy was 20 days (range 9-34); median time from blood draw to receiving the cfDNA findings was 9 days (range 7-12). The median difference between the cfDNA and the tumor analysis reports was 20 days (range 9-28). Actionable biomarkers were identified in four patients by both the biopsy analysis and the cfDNA analysis (2cases with EGFR mutations, one with ROS1 fusion, and one with EML4-ALK fusion for whom the biopsy analysis also identified an EGFR mutation not detected in the cfDNA analysis). Overall, eight patients received treatment (2 died before treatment initiation). Three patients received biomarker-based treatment (1 osimertinib, 1 alectinib, and 1 crizotinib). CONCLUSIONS: These findings suggest that cfDNA analysis should be ordered by the pulmonologists early in the evaluation of patients with NSCLC, which might complement the tumor biopsy.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Acrilamidas/uso terapêutico , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/uso terapêutico , DNA de Neoplasias/sangue , Feminino , Técnicas de Genotipagem , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Piperidinas/uso terapêutico , Estudos Prospectivos
7.
Gan To Kagaku Ryoho ; 47(12): 1711-1714, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33342989

RESUMO

A 70-year-old man who was diagnosed with a cStage ⅣA lung adenocarcinoma was in a stable condition for a long time after the first chemotherapy with gefitinib. However, 2 years 4 months later, the lung cancer progressed, and he was diagnosed with Stage Ⅲ gastric cancer. Since the administration of afatinib as the second-line chemotherapy was ineffective, nivolumab was administered as the third-line chemotherapy. The lung cancer showed a partial response to nivolumab treatment, but the gastric cancer remained unresponsive. We report a rare case of immune checkpoint inhibitor administration for synchronous double primary cancers.


Assuntos
Neoplasias Pulmonares , Neoplasias Gástricas , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Humanos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico
8.
Anticancer Res ; 40(12): 7089-7094, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288607

RESUMO

BACKGROUND/AIM: We investigated the relationship between solid component size (SS), carcinoembryonic antigen (CEA), and standardized uptake value (SUVmax) as continuous variables and postoperative clustered circulating tumor cell (C-CTC) detection in patients with pulmonary adenocarcinoma who underwent surgery. PATIENTS AND METHODS: C-CTC detection was the main evaluation item, which was analyzed using the receiver operating characteristic curve to calculate areas under the curves (AUCs) for the variables. Additionally, the two-year recurrence-free survival rates (2Y-RFSRs) were analyzed. RESULTS: Among the 84 patients examined, SS, CEA, and SUVmax had AUCs>0.7, and were independent. Their thresholds were 2.1 cm, 7.5 ng/ml, and 2.9, respectively. The 2Y-RFSR were significantly better in the non-C-CTC group (n=58) and in the group of patients without high levels of these predictors (n=32). CONCLUSION: SS, CEA level, and SUVmax predicted postoperative CTC detection in pulmonary adenocarcinoma patients.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma de Pulmão/patologia , Idoso , Humanos , Masculino , Prognóstico
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(10): 1149-1154, 2020 Oct 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33268574

RESUMO

OBJECTIVES: To explore the expression of programmed death ligand-1 (PD-L1) as well as the correlation between the expression and the clinicopathological features or prognosis in non-small cell lung cancer (NSCLC). METHODS: The expression of PD-L1 protein in 254 cases of surgically resected lung adenocarcinoma (L-ADC), 228 cases of surgically resected lung squamous cell cancer (L-SCC), and 99 cases of non-cancerous control lung tissues was detected with immunohistochemical SP method. The correlation between the PD-L1 expression and clinicopathological features was analyzed. Kaplan-Meier univariate and Cox multivariate regression analyses were performed to assess the prognosis of patients with L-ADC and L-SCC, respectively. RESULTS: Positive percentage of PD-L1 protein expression was higher in the tissues of L-ADC and L-SCC than that in the non-cancerous control lung tissues respectively (both P<0.05). Positive percentage of PD-L1 protein expression was higher in the tissues of L-SCC than that in the tissues of L-ADC (P<0.05). However, there were no correlation between the expression of PD-L1 and age, gender, pathological grades, clinical stages, and lymph node metastasis in L-ADC and L-SCC respectively (all P>0.05). Overall survival rate was evidently lower in the L-ADC patients with positive expression of PD-L1 protein compared to the patients with negative staining of PD-L1 (P<0.01). Multivariate Cox regression analysis further identified that the L-ADC patients of positive expression of PD-L1 protein had a poor prognosis (P<0.01). CONCLUSIONS: The positive percentage of PD-L1 protein expression is higher in the L-SCC patients than that in the L-ADC patients. Positive expression of PD-L1 protein can be served as an independent prognostic factor of poor prognosis in the patients with L-ADC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão , Antígeno B7-H1/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Pacientes , Prognóstico
10.
Kyobu Geka ; 73(13): 1125-1127, 2020 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-33271587

RESUMO

A 61-year-old woman, who was revealed to have a 11 mm pulmonary nodule in the right middle lobe by computed tomography, was diagnosed with adenocarcinoma using bronchoscopy. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed FDG accumulation in the tumor, with a maximum standardized uptake value( SUVmax) of 2.47. Therefore, she underwent thoracoscopic right middle lobectomy. Histopathological examination revealed invasive growth of cylindrical tumor cells with clear glycogen-filled cytoplasm and a relatively high-grade nuclear atypia in tubulopapillary structures; no morula was observed. Immunohistochemically, the membranes of the tumor cells were positively stained for ß-catenin, indicating high-grade fetal adenocarcinoma (pT1bN0M0, pathologic stageⅠA2). The postoperative course was uneventful, without recurrence 6 months after surgery.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares , Adenocarcinoma de Pulmão , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
11.
Medicine (Baltimore) ; 99(46): e23150, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181687

RESUMO

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) have become the preferred therapy as first-line treatment of non-small cell lung cancer patients harboring sensitizing EGFR mutations. However, the prognostic indicators are limited. The present study aimed to assess the prognostic value of immune-inflammation factors, fibrinogen-albumin ratio index (FARI), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in EGFR-Mutant lung adenocarcinoma patients receiving first-generation EGFR-TKIs treatment.194 patients were included in this retrospective analysis. FARI was calculated as fibrinogen / albumin. Receiver operating characteristic curve was used to evaluate the optimal cut-off value for FARI, NLR, and PLR to progression free survival (PFS). Univariate and multivariate survival analysis were performed to identify factors correlated with PFS and overall survival (OS).Applying cut-offs of ≥0.08 (FARI), ≥3.28 (NLR), and ≥273.85 (PLR), higher FARI or NLR was associated with worse Eastern Cooperative Oncology Group performance status (ECOG PS) (P = .018, .002, respectively), and there were more males in high NLR group (P = .043). In univariate analysis, ECOG PS status, NLR, PLR, and FARI were significantly associated with PFS (P = .017, .004, <.001, .001, respectively) as well as OS (P < .001, = .001, .002, .023, respectively). In multivariate analysis, PLR (hazard ratios [HR] 1.692; 95% CI 1.054-2.715; P = .029) and FARI (HR 1.496; 95% CI 1.031-2.172; P = .034) were independent prognostic factors for PFS. While only ECOG PS status (HR 2.052; 95% CI 1.272-3.310; P = .003) was independently correlated with OS.FARI is independently associated with PFS in EGFR-Mutant lung adenocarcinoma patients receiving first-line EGFR-TKIs treatment.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB/genética , Fibrinogênio/análise , Inibidores de Proteínas Quinases/uso terapêutico , Albumina Sérica Humana/análise , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores/sangue , Contagem de Células Sanguíneas/métodos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão
12.
Medicine (Baltimore) ; 99(45): e22631, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157918

RESUMO

RATIONALE: The anaplastic lymphoma kinase (ALK) fusion has been identified to be a driver gene in lung cancer, and serves as important diagnostic and therapeutic targets. Owing to the advanced sequencing technologies, new partner genes of ALK have been constantly detected. PATIENT CONCERNS: A 55-year-old Chinese woman went to our hospital because of cough and expectoration for 1 year. The patient had no fever, chest pain and hemoptysis. DIAGNOSES: She was diagnosed with lung adenocarcinoma. Because she had no operational condition, combination chemotherapy with docetaxel and cisplatin (CP) for 4 cycles was adopted. However, computed tomography (CT) scan indicated progression disease (PD). To explore possibility of targeted therapy, the tumor samples were subjected to next-generation sequencing (NGS), and a rare double ALK fusion variant EML4-ALK and CDK15-ALK was identified. INTERVENTIONS AND OUTCOMES: The patient subsequently received crizotinib treatment, and achieved partial response (PR). No significant drug related adverse reactions were found during crizotinib treatment. The progression-free survival achieved 23 months. LESSONS: Together, we identified a rare double ALK fusion variant, EML4-ALK and CDK15-ALK, in a patient with lung adenocarcinoma. The patient benefited from crizotinib treatment, which could provide a certain reference for the patients with such gene alteration.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Crizotinibe/uso terapêutico , Quinases Ciclina-Dependentes/genética , Proteínas de Fusão Oncogênica/genética , Adenocarcinoma de Pulmão/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
13.
Medicine (Baltimore) ; 99(45): e23114, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157987

RESUMO

To investigate the value of percentile base on computed tomography (CT) histogram analysis for distinguishing invasive adenocarcinoma (IA) from adenocarcinoma in situ (AIS) or micro invasive adenocarcinoma (MIA) appearing as pure ground-glass nodules.A total of 42 cases of pure ground-glass nodules that were surgically resected and pathologically confirmed as lung adenocarcinoma between January 2015 and May 2019 were included. Cases were divided into IA and AIS/MIA in the study. The percentile on CT histogram was compared between the 2 groups. Univariate and multivariate logistic regression were used to determine which factors demonstrated a significant effect on invasiveness. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was used to evaluate the predictive ability of individual characteristics and the combined model.The 4 histogram parameters (25th percentile, 55th percentile, 95th percentile, 97.5th percentile) and the combined model all showed a certain diagnostic value. The combined model demonstrated the best diagnostic performance. The AUC values were as follows: 25th percentile = 0.693, 55th percentile = 0.706, 95th percentile = 0.713, 97.5th percentile = 0.710, and combined model = 0.837 (all P < .05).The percentile of histogram parameters help to improve the ability to radiologically determine the invasiveness of lung adenocarcinoma appearing as pure ground-glass nodules.


Assuntos
Adenocarcinoma in Situ/diagnóstico por imagem , Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Área Sob a Curva , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/estatística & dados numéricos
14.
PLoS Genet ; 16(11): e1009168, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33137086

RESUMO

MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function in de novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human lung cancer miRNA database, we identified 16 downregulated miRNAs associated with malignant progression and performed individual knockout with dgRNA system in KrasG12D/Trp53L/L (KP) mouse model. Using this in vivo knockout screening, we identified miR-30b and miR-146a, which has been previously reported as tumor suppressors and miR-190b, a new tumor-suppressive miRNA in lung cancer development. Over-expression of miR-190b in KP model as well as human lung cancer cell lines significantly suppressed malignant progression. We further found that miR-190b targeted the Hus1 gene and knockout of Hus1 in KP model dramatically suppressed lung tumorigenesis. Collectively, our study developed an in vivo miRNA knockout platform for functionally screening in GEMM and identified miR-190b as a new tumor suppressor in lung cancer.


Assuntos
Adenocarcinoma de Pulmão/genética , Proteínas de Ciclo Celular/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Biologia Computacional , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células HEK293 , Humanos , Estimativa de Kaplan-Meier , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Knockout , MicroRNAs/genética , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
16.
Yonsei Med J ; 61(12): 1013-1023, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33251775

RESUMO

PURPOSE: Most lung adenocarcinoma (LUAD) patients are diagnosed at the advanced stage and have poor prognosis. DNA methylation plays an important role in the prognosis prediction of cancers. The objective of this study was to identify new DNA methylation sites as biomarkers for LUAD prognosis. MATERIALS AND METHODS: We downloaded DNA methylation data from The Cancer Genome Atlas data portal. Cox proportional hazard regression model and random survival forest algorithm were applied to identify the DNA-methylation sites. Methylation of sites were validated in the Gene Expression Omnibus cohorts. Function annotation were done to explore the biological function of DNA methylated sites signature. RESULTS: Six DNA methylation sites were identified as prognosis signature. The signature yielded acceptable discrimination between the high-risk group and low-risk group. The discrimination effect of this DNA methylation signature for the OS was obvious, with a median OS of 21.89 months vs. 17.74 months for high-risk vs. low-risk groups. This prognostic prediction model was validated by the test group and GEO dataset. The predictive survival value was higher for the prognostic prediction model than that for the tumor node metastasis stage. Adjuvant hemotherapy could not affect the prediction of the signature. Functional analysis indicated that these signature genes were involved in protein binding and cytoplasm. CONCLUSION: We identified the prognostic signature for LUAD by combining six DNA methylation sites. This could service as potential robust and specificity signature in the prognosis prediction of LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Programas de Rastreamento/métodos , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biomarcadores Tumorais/genética , Feminino , Genes , Genes Neoplásicos/genética , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
17.
Kyobu Geka ; 73(11): 920-923, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33130714

RESUMO

A 71-year-old man with a history of smoking 1 pack of cigarettes per day for the past 53 years visited our department with chest pain, and was diagnosed as spontaneous pneumothorax. A chest computed tomography scan revealed a nodular shadow in the upper portion of the left lobe of the lung, which was found to be adenocarcinoma by transbronchial lung biopsy. A left upper lobectomy and lymphadenectomy were performed. The pathological diagnosis was a high-grade fetal lung adenocarcinoma (H-FLAC) with a hepatoid adenocarcinoma component (pT2aN0M0, pStage I B). H-FLAC comprises at least 50% fetal lung-like cells, while hepatoid adenocarcinoma comprises hepatocellular carcinoma-like cells. Following the diagnosis, adjuvant chemotherapy with uracil-tegafur was started. Although both these neoplasms are known to have a poor prognosis, no recurrences were observed at 11 months postsurgery.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Pulmonares , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Idoso , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Recidiva Local de Neoplasia
18.
Nat Commun ; 11(1): 6083, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247113

RESUMO

The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Receptores ErbB/genética , Frequência do Gene/genética , Genes Dominantes , Humanos , Mutação/genética , Invasividade Neoplásica , Estadiamento de Neoplasias , Filogenia
19.
Chem Biol Interact ; 332: 109304, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33164868

RESUMO

Cisplatin-based chemotherapy is a common first-line regimen for treating non-small cell lung cancer (NSCLC). However, drug resistance is still a major problem. The purposes of this study were to evaluate whether sclareol can reverse cisplatin resistance and to investigate its possible mechanisms. A549 cells, the human NSCLC cells with inherent cisplatin resistance, were used to investigate synergistic effect of sclareol with cisplatin in cell proliferation and migration as well as its regulatory mechanisms in expression of excision repair cross-complementation group 1 (ERCC1), a cisplatin resistance-associated molecule. Nude mice bearing subcutaneous A549 tumors were applied to investigate synergistic activity of sclareol in anti-tumor. As comparing to the cisplatin alone group, the treatment of cisplatin combined with sclareol significantly suppressed survival rate and cell migration of A549 cells. Besides, sclareol also exhibited suppression in ERCC1 expression by inhibiting AKT-GSK3ß-AP1/Snail and JNK-AP1 pathways. Furthermore, the experimental data from in vivo study also demonstrated that the combination group of cisplatin and sclareol showed the greatest anti-tumor activity, whose effect could be partially attributed to sclareol-mediated decrease in intratumoral level of ERCC1 protein. Accordingly, sclareol has potential as an adjuvant for the treatment in NSCLC patients with cisplatin resistance.


Assuntos
Adenocarcinoma de Pulmão/patologia , Cisplatino/farmacologia , Diterpenos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína de Replicação C/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Células A549 , Animais , Movimento Celular/efeitos dos fármacos , Diterpenos/química , Sinergismo Farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Camundongos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Transcrição AP-1/metabolismo
20.
Nat Commun ; 11(1): 5712, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177501

RESUMO

Nearly half of the human genome is made of transposable elements (TEs) whose activity continues to impact its structure and function. Among them, Long INterspersed Element class 1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed and mobilized in different cancers, generating mutagenic insertions that could affect tumor malignancy. Tumor suppressor microRNAs are ∼22nt RNAs that post-transcriptionally regulate oncogene expression and are frequently downregulated in cancer. Here we explore whether they also influence L1 mobilization. We show that downregulation of let-7 correlates with accumulation of L1 insertions in human lung cancer. Furthermore, we demonstrate that let-7 binds to the L1 mRNA and impairs the translation of the second L1-encoded protein, ORF2p, reducing its mobilization. Overall, our data reveals that let-7, one of the most relevant microRNAs, maintains somatic genome integrity by restricting L1 retrotransposition.


Assuntos
Elementos Nucleotídeos Longos e Dispersos/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Adenocarcinoma de Pulmão/genética , Sítios de Ligação , Carcinoma de Células Escamosas/genética , Endonucleases/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , DNA Polimerase Dirigida por RNA/genética , Células Tumorais Cultivadas , Sequenciamento Completo do Genoma
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