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BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.
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Neoplasias Encefálicas , Glioma , Biomarcadores , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular/genética , Glioma/patología , Humanos , FN-kappa B , Proteínas Nucleares/genética , PronósticoRESUMEN
The optimal time to the initiation of postoperative radiotherapy (TTR) in breast cancer patients after neoadjuvant chemotherapy (NAC) and surgery is unclear. We explored the association between TTR and outcomes among breast cancer females to determine the optimal timing for radiotherapy. We included 1022 women with breast cancer who underwent NAC and surgery between 1997 and 2019. Patients were categorized into three groups based on the TTR: <8 weeks, 8 to 16 weeks and >16 weeks. We used Cox proportional hazards models and analyzed the hazard ratios (HRs) for breast cancer-specific mortality (BCSM) and all-cause mortality (ACM). The median TTR for the cohort was 97 days. Compared to patients with TTRs of 8 to 16 weeks, those with TTRs <8 weeks or >16 weeks had an increased risk of BCSM (HR, 2.59; 95% confidence interval [CI], 1.26-5.36 and HR, 2.01; 95% CI, 1.24-3.28, respectively) and ACM (HR, 2.32; 95% CI, 1.17-4.56 and HR, 1.92; 95% CI, 1.24-2.98, respectively) after adjusting for the confounders. Furthermore, at TTR of >16 weeks, each additional week of TTR was associated with a 3% increase in BCSM risk and 2% increase in ACM risk. Our findings suggest that patients who have undergone NAC and surgery show lower BCSM and ACM risks at TTR of 8 to 16 weeks compared to <8 weeks or >16 weeks.
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Neoplasias de la Mama , Terapia Neoadyuvante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Estudios de Cohortes , Femenino , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Little is known about whether age at initial diagnosis influences the prognosis of recurrent metastatic breast cancer (rMBC). Here, we analyzed the association between age at initial diagnosis and rMBC mortality in China. METHODS: A total of 1636 women diagnosed with rMBC between 1989 and 2020 at West China Hospital, Sichuan University were included in this study. The age at initial diagnosis was categorized as young (≤ 40 years), middle-aged (41-64 years) and elderly (≥ 65 years). Post-metastasis mortality was the primary outcome and its associated factors were analyzed by Cox proportional hazards models. RESULTS: During a median follow-up of 5.2 years after initial diagnosis of breast cancer, 620 deaths were identified. Compared with middle-aged patients, elderly patients had a 70% increased risk of post-metastasis mortality (95%CI, 1.24-2.33) after adjusting for demographics, tumor characteristics and treatment modes. Similarly, elderly patients were associated with a 75% increased risk of post-metastasis mortality (95%CI, 1.19-2.59) compared with young patients. Subgroup analyses also showed similar trends. CONCLUSION: Our findings suggest that in breast cancer, elderly patients at initial diagnosis face a higher risk of post-metastasis mortality.
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Neoplasias de la Mama , Anciano , Neoplasias de la Mama/patología , China/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVES: Although metastatic breast cancer (MBC) is considered incurable, a specific subset of patients exhibits prolonged survival and even achieve a "cure". We retrospectively identified predictive prognostic factors and systemic therapy models to find this group of potentially cured patients. METHODS: Consecutive patients diagnosed with MBC from 1991-2016 in West China Hospital were included. Univariate and multivariate analyses were conducted to assess the association of clinical factors and systemic therapy models with overall survival (OS), breast cancer-specific survival (BCSS) and progression-free survival (PFS). RESULTS: The median OS was 63.4 months. Age, tumor size, lymph node metastasis, histologic grade, molecular subtype, site and number of metastases and metastasis-free interval (MFI) were related to the prognosis of MBC (P < .05). Patients with T1, N0-1, luminal A, bone metastasis, OMBC (oligometastatic breast cancer) or metastasis-free interval (MFI) ≥ 3 years showed the median OS more than 10 years (P < .001). Independent prognostic factors that correlated with OS and BCSS were residence, lymph node metastasis, histologic grade, molecular subtype, and site of metastasis (P < .05). The group of sequential chemo-endocrine therapy (ST) in hormone receptor (HR)-positive MBC patients showed the highest overall response rate (ORR) (P < .05). However, patients who received endocrine therapy (ET) showed the best OS, BCSS and PFS in the first two-line treatment, followed by ST and chemotherapy (CT) (P < .05). CONCLUSIONS: Our study shows the predictive prognostic factors and systemic therapy models to facilitate patients likely to achieve long-term survival.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Metástasis de la Neoplasia , Pronóstico , Receptor ErbB-2/metabolismo , Estudios RetrospectivosRESUMEN
The well-known proto-oncogene rearrangement during transfection (RET), also known as ret proto-oncogene Homo sapiens (human), is a rare gene that is involved in the physiological development of some organ systems and can activate various cancers, such as non-small cell lung cancer, thyroid cancer, and papillary thyroid cancer. In the past few years, cancers with RET alterations have been treated with multikinase inhibitors (MKIs). However, because of off-target effects, these MKIs have developed drug resistance and some unacceptable adverse effects. Therefore, these MKIs are limited in their clinical application. Thus, the novel highly potent and RET-specific inhibitors selpercatinib and pralsetinib have been accelerated for approval by the Food and Drug Administration (FDA), and clinical trials of TPX-0046 and zetletinib are underway. It is well tolerated and a potential therapeutic for RET-altered cancers. Thus, we will focus on current state-of-the-art therapeutics with these novel RET inhibitors and show their efficacy and safety in therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias de la Tiroides , Estados Unidos , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-ret/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer-specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer-specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer-specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow-up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer-specific mortality (95% CI 0%-65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer-specific mortality (95% CI 11%-82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%-12%) reduction in cancer-specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%-39%). Our findings suggest that underinsured patients face a higher risk of breast cancer-specific mortality in developing countries.
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Neoplasias de la Mama/mortalidad , Cobertura del Seguro/estadística & datos numéricos , Seguro de Salud/estadística & datos numéricos , Programas Nacionales de Salud/estadística & datos numéricos , Adolescente , Adulto , Neoplasias de la Mama/economía , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Cobertura del Seguro/economía , Seguro de Salud/economía , Reembolso de Seguro de Salud/economía , Reembolso de Seguro de Salud/estadística & datos numéricos , Persona de Mediana Edad , Programas Nacionales de Salud/economía , Pronóstico , Estudios Prospectivos , Medición de Riesgo/estadística & datos numéricos , Servicios de Salud Rural/economía , Servicios de Salud Rural/estadística & datos numéricos , Clase Social , Servicios Urbanos de Salud/economía , Servicios Urbanos de Salud/estadística & datos numéricos , Adulto JovenRESUMEN
Oncogenic fusion gene Echinoderm Microtubule-associated protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) contributes to tumorigenesis of a subset of non-small cell lung cancer (NSCLC). Recently, we demonstrated that F-circEA-4a, a tumor-promoting circular RNA (circRNA) generated from the back-splicing of EML4-ALK variant 3b (v3b), is a novel liquid biopsy biomarker for NSCLC. However, circRNAs produced from EML4-ALK gene and their roles in NSCLC are not well-characterized. Here, we identify another EML4-ALK-v3b-derived circRNA, F-circEA-2a, harboring "AA" (rather than "AAAA" in F-circEA-4a) motif at the junction site. F-circEA-2a mainly locates in the cytoplasm and promotes cell migration and invasion, but has little effect on cell proliferation. Moreover, F-circEA-2a exists in tumor, but not in the plasma of NSCLC patients with EML4-ALK fusion gene, further supporting the significant diagnostic value of F-circEA-4a for EML4-ALK-positive NSCLC. This work finds a novel oncogenic circRNA generated from EML4-ALK fusion gene, highlighting the pivotal role of circRNA in EML4-ALK-positive NSCLC development.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Proteínas de Fusión Oncogénica/genética , ARN/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Puntos de Rotura del Cromosoma , Humanos , Neoplasias Pulmonares/patología , ARN Circular , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To determine the effect of downregulation of 53BP1 expression on cell growth and radiosensitivity in laryngeal carcinoma Hep-2 cells. METHODS: HEP-2 cell lines were established with a stable knockdown of 53BP1 with short hairpin RNA (shRNA). The level of expressed protein of negative control group (NC),wild type Hep-2 and downregulation of 53BP1 (P6) group was determined by Western blotting. Proliferation on normal conditions was detected by MTT. Radiosensitivity and growth of cells were detected by flow cytometry. RESULTS: A stable 53BP1 downregulated cell line P6 was established. Similar cell growth was observed between the 53BP1 downregulated cells and the control cells. The downregulation of 53BP1 reduced the number of clonogenic cells exposed to radiation. Compared with wild type Hep-2 group and NC group, Western blot results showed a decrease in 53BP1 protein level in P6 group (P < 0.05), reducing the ratio of arrest of G2/M with radiation dose increased (P < 0.05). MTT results revealed the lower 53BP1 protein level did not affect the cell proliferation. After exposure to 0, 2, 6, 10 Gy ionizing radiation (IR), P6 cells had lower, radiosensitivity parameters (D0, SF2, Dq, N) than controls and wild type Hep-2 (P < 0.05). CONCLUSION: RNA interference could effectively down-regulate the expression of 53BP1 and reduce arrest of G2/M phase, thus enhancing the radiosensitivity of Hep-2 cell line.
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Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Laríngeas/metabolismo , ARN Interferente Pequeño , Tolerancia a Radiación , Puntos de Control del Ciclo Celular , Línea Celular Tumoral/efectos de la radiación , Proliferación Celular , Regulación hacia Abajo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Interferencia de ARN , Transfección , Proteína 1 de Unión al Supresor Tumoral P53RESUMEN
Lung cancer is still the leading cause of cancer-related mortality. Over the past two decades, the management of non-small cell lung cancer (NSCLC) has undergone a significant revolution. Since the first identification of activating mutations in the epidermal growth factor receptor (EGFR) gene in 2004, several genetic aberrations, such as anaplastic lymphoma kinase rearrangements (ALK), neurotrophic tropomyosin receptor kinase (NTRK) and hepatocyte growth factor receptor (MET), have been found. With the development of gene sequencing technology, the development of targeted drugs for rare mutations, such as multikinase inhibitors, has provided new strategies for treating lung cancer patients with rare mutations. Patients who harbor this type of oncologic driver might acquire a greater survival benefit from the use of targeted therapy than from the use of chemotherapy and immunotherapy. To date, more new agents and regimens can achieve satisfactory results in patients with NSCLC. In this review, we focus on recent advances and highlight the new approval of molecular targeted therapy for NSCLC patients with rare oncologic drivers.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Molecular Dirigida , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/genética , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/genética , Antineoplásicos/uso terapéuticoRESUMEN
E2F transcription factors (E2Fs) are a group of genes that encode a family of transcription factors. They have been identified as being involved in the tumor progression of various cancer types. However, little is known about the expression level, genetic variation, molecular mechanism, and prognostic value and immune infiltration of different E2Fs in HNSCC.In this study, we utilized multiple databases to investigate the mRNA expression level, genetic alteration, and biological function of E2Fs in HNSCC patients. Then, the relationship between E2Fs expression and its association with the occurrence, progress, prognosis, and immune cell infiltration in patients with HNSCC was evaluated. We found that all eight E2Fs were higher expressed in HNSCC tissues than in normal tissues, and the expression levels of E2F1/2/3/4/5/6/8 were also associated with the stage and grade of HNSCC. The abnormal expression of E2F1/2/4/8 in HNSCC patients is related to the clinical outcome. The expression of E2Fs was statistically correlated with the immune cell infiltration in HNSCC and the infiltration of B cells and CD8+ T cells were positively associated with better OS in HNSCC patients. Furthermore, we verified the E2F2 at the tissue level in the validation experiment. Our study may provide novel insights into the choice of immunotherapy targets and potential prognostic biomarkers in HNSCC patients.
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Factores de Transcripción E2F , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Linfocitos T CD8-positivos/inmunología , Regulación Neoplásica de la Expresión Génica , Estadificación de Neoplasias , Linfocitos Infiltrantes de Tumor/inmunologíaRESUMEN
Background: For adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high rate of mortality and recurrence, it is difficult for clinicians to predict overall survival and select the most effective treatment. Targeting ferroptosis, a form of cell death, has been reported to be a promising therapeutic strategy for ACC; however, the core ferroptosis regulator and its prognostic value in ACC remain unknown. Methods: RNA sequencing data and clinical information were downloaded from public databases. Differentially expressed gene and survival analyses were performed to identify candidate ferroptosis regulators. A multivariate Cox regression model was used to construct a gene signature, and a nomogram was constructed to predict the overall survival of patients with ACC. Gene set variation analysis (GSVA) was used to identify underlying aberrant pathways and the relative immune cell infiltration levels of each ACC sample. Immunohistochemistry staining was performed in formalin-fixed paraffin-embedded tumor tissue sections. Results: Ultimately, 23 differentially expressed ferroptosis regulators were identified between normal adrenal gland and ACC tissues, and 50 ferroptosis regulators were related to prognosis, with 13 ferroptosis regulators being simultaneously found to satisfy the differential expression and prognostic value. According to the multivariate Cox regression model, a ferroptosis regulator signature was constructed from 3 genes in The Cancer Genome Atlas (TCGA; hazard ratio =9.01; P=1.39×10-10), and the area under the curve (AUC) values of 3-, 5-, 8-year overall survival were 0.924, 0.906, and 0.866, respectively. The survival analysis and the receiver operating characteristic (ROC) analysis validated the prognostic value of the ferroptosis regulator signature in 3 validation datasets. Moreover, metabolism-, E2F-, MYC-, and G2/M checkpoint-related pathways and aberrant immune cell infiltration levels were identified as being responsible for the different prognosis of risk groups in ACC. HELLS was found to be a significantly differentially expressed ferroptosis-suppressor gene with a prognostic value in ACC and to be highly associated with immune cell infiltration levels and multiple biological functions. Conclusions: A ferroptosis regulator signature showed promising power for predicting the prognosis of ACC, and HELLS was identified as a hub ferroptosis regulator in the initiation and progression of ACC.
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The effect of long noncoding RNAs (lncRNAs) on the radiotherapy response has been gradually revealed. This systematic review and meta-analysis aimed to evaluate the association between the function and underlying mechanism of lncRNAs in regulating the radiosensitivity and radioresistance of different tumors. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to estimate the effect of lncRNAs on cancer patient prognosis, including overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS) and progression-free survival (PFS). Collectively, 23 lncRNAs in 11 cancer types were enrolled. Of them, 13 lncRNAs were downregulated and related to radiosensitivity, 11 lncRNAs were upregulated and related to radioresistance, and 3 lncRNAs were upregulated and related to radiosensitivity in cancers. Furthermore, 17 microRNAs and 20 pathways were targeted by different lncRNAs and contributed to the cancer radiotherapy response in this meta-analysis. The individual pooled HRs (95% CIs) of downregulated radiation-resistant and upregulated radiation-resistant lncRNAs for OS were 0.49 (0.40-0.60) and 1.88 (1.26-2.79), respectively. Our results showed that lncRNAs could modulate tumor radioresistance or sensitivity by affecting radiation-related signaling pathways and serve as potential biomarkers to predict radiotherapy response.
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MicroARNs , Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Neoplasias/genética , Neoplasias/radioterapiaRESUMEN
Background: Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a novel rare disease after the 2016 WHO reclassification. Surgery is the main treatment. Postoperative adjuvant radiotherapy is often used, but the effects of different radiotherapy techniques are still unclear. The purpose of this study was to analyze the effects of postoperative radiotherapy (PORT) and different radiotherapy methods on the efficacy of patients with intracranial SFT/HPC. Materials and methods: We retrospectively analyzed 42 patients with intracranial SFT/HPC who underwent surgical treatment from 2008 to 2022, 20 of whom were treated with postoperative intensity-modulated radiotherapy (IMRT) and 22 with postoperative stereotactic radiosurgery (SRS). The Kaplan-Meier method was used to analyze the disease-free survival (DFS) of all the 42 patients receiving postoperative radiotherapy and the time to progression (TTP) of 22 of these patients experiencing recurrence. A multivariate Cox proportional hazards model was used to detect prognostic factors of survival. Results: In the analysis of PORT patients, the median DFS was 8.33 years for PORT IMRT patients and 3.04 years for PORT SRS patients. The 10-year DFS incidence was 46.0% in the PORT IMRT group and 27.5% in the SRS group. Among the 22 patients who relapsed, the median TTP of other patients was 1.25 years, of which 3 received radiotherapy alone and 1 received symptomatic treatment, while the median TTP of surgical and surgical combined with radiotheray patients were 1.83 and 2.49 years, respectively (p=0.035). Conclusion: PORT IMRT could prolong DFS compared with PORT SRS. It indicated that PORT IMRT radiotherapy technology was a feasible option for SFT/HPC. Moreover, TTP results of relapsed patients showed that, surgery and surgery combined with radiotherapy treatments have no significant difference on TTP in relapsed patients, but both of them were better than other treatments.
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There is an urgent need to identify reliable biomarkers that can be used in early diagnosis, prognostication prediction and as possible therapeutic targets for lung cancer due to its current poor prognosis. Long noncoding RNAs (lncRNAs) have recently attracted additional attention due to their potential role in carcinogenesis, invasion and metastasis. Issues involved in the biofunctions and regulatory mechanisms of oncogenic and tumor-suppressive lncRNAs in lung cancer are discussed. Some lncRNAs have shown good diagnostic value, especially in combination with conventional serum protein markers. The use of antisense oligonucleotides, small molecules and RNA interference techniques have shown promise as direct therapeutic tools for targeting lncRNAs in preclinical studies. The biomarker function of lncRNAs may also indirectly involved in tumor therapy as a reference to conventional therapy. Overall, the concept of using lncRNAs as biomarkers for prognostication and intervention in lung cancer is still in its infancy, and only with more in-depth studies could they have a significant impact.
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BACKGROUND: Little is known about the benefits of adjuvant endocrine therapy (ET) in low ER-positive breast cancer (1%-10%) patients. We analyzed the association between ET and breast cancer-specific survival (BCSS) in these patients with respect to the regimen and the duration of ET. METHODS: Patients were classified into three groups based on the regimen and duration of ET. The regimens included aromatase inhibitor (AI) monotherapy or sequential tamoxifen followed by an AI (AI/T + AI), or only tamoxifen and no ET. The duration of ET included 2-3 years and >3 years. Multivariate Cox regression analysis was employed to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of the 10,696 patients diagnosed with breast cancer between 2010 and 2020, 407 women were identified with ER-low positive disease and met the inclusion criteria. During a median follow-up of 5.2 years, patients who received ET improved BCSS. Of them, those with AI/T + AI had increased BCSS compared to patients without ET, after adjusting for demographics and tumor characteristics, especially in ER-low/HER-2-positive breast cancer. After additional adjustment for treatment mode, the association maintained a similar trend. Patients who received >3 years of ET was associated with a better DFS. There was no significant difference in BCSS between patients with 2-3 years and >3 years of ET. CONCLUSION: For ER-low patients, findings suggest that ET with AI/T + AI may be a reasonable treatment alternative. This effect should be assessed in randomized studies.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Receptores de Estrógenos , Antineoplásicos Hormonales/uso terapéutico , Estudios Prospectivos , Tamoxifeno/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Quimioterapia Adyuvante/métodosRESUMEN
Objectives: The weak health system, domestic political unrest, poverty, and many other factors in the Central African Republic (CAR) have left the country underprepared for the COVID-19 pandemic, resulting in a greater health threat to the entire country. Rapid measures must therefore be taken to prevent the further spread of COVID-19. Methods: This work encompassed a review of relevant literature. We aim to analyze how far Chinese COVID measures can be transferred to the context of the CAR. Results: We argue that the measure that the CAR can learn from China's success is the involvement of community workers and that greater investment in this model may be the optimal solution. Help from the international community is urgently needed. Conclusion: The CAR can benefit from China's successful experience in fighting the epidemic, but the disparity in the combined power of the two countries does not allow for simple replication of China's strategy.
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COVID-19 , Adaptación Psicológica , COVID-19/epidemiología , República Centroafricana/epidemiología , China/epidemiología , Humanos , PandemiasRESUMEN
The accurate prediction of the status of PLNM preoperatively plays a key role in treatment strategy decisions in early-stage cervical cancer. The aim of this study was to develop and validate a radiomics-based nomogram for the preoperative prediction of pelvic lymph node metastatic status in early-stage cervical cancer. One hundred fifty patients were enrolled in this study. Radiomics features were extracted from T2-weighted MRI imaging (T2WI). Based on the selected features, a support vector machine (SVM) algorithm was used to build the radiomics signature. The radiomics-based nomogram was developed incorporating radiomics signature and clinical risk factors. In the training cohort (AUC = 0.925, accuracy = 81.6%, sensitivity = 70.3%, and specificity = 92.0%) and the testing cohort (AUC = 0.839, accuracy = 74.2%, sensitivity = 65.7%, and specificity = 82.8%), clinical models that combine stromal invasion depth, FIGO stage, and MTD perform poorly. The combined model had the highest AUC in the training cohort (AUC = 0.988, accuracy = 95.9%, sensitivity = 92.0%, and specificity = 100.0%) and the testing cohort (AUC = 0.922, accuracy = 87.1%, sensitivity = 85.7%, and specificity = 88.6%) when compared to the radiomics and clinical models. The study may provide valuable guidance for clinical physicians regarding the treatment strategies for early-stage cervical cancer patients.
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Background: The role of the tumor microenvironment (TME) in predicting prognosis and therapeutic efficacy has been demonstrated. Nonetheless, no systematic studies have focused on TME patterns or their function in the effectiveness of immunotherapy in triple-negative breast cancer. Methods: We comprehensively estimated the TME infiltration patterns of 491 TNBC patients from four independent cohorts, and three cohorts that received immunotherapy were used for validation. The TME subtypes were comprehensively evaluated based on immune cell infiltration levels in TNBC, and the TRG score was identified and systematically correlated with representative tumor characteristics. We sequenced 80 TNBC samples as an external validation cohort to make our conclusions more convincing. Results: Two TME subtypes were identified and were highly correlated with immune cell infiltration levels and immune-related pathways. More representative TME-related gene (TRG) scores calculated by machine learning could reflect the fundamental characteristics of TME subtypes and predict the efficacy of immunotherapy and the prognosis of TNBC patients. A low TRG score, characterized by activation of immunity and ferroptosis, indicated an activated TME phenotype and better prognosis. A low TRG score showed a better response to immunotherapy in TNBC by TIDE (Tumor Immune Dysfunction and Exclusion) analysis and sensitivity to multiple drugs in GDSC (Genomics of Drug Sensitivity in Cancer) analysis and a significant therapeutic advantage in patients in the three immunotherapy cohorts. Conclusion: TME subtypes played an essential role in assessing the diversity and complexity of the TME in TNBC. The TRG score could be used to evaluate the TME of an individual tumor to enhance our understanding of the TME and guide more effective immunotherapy strategies.
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BACKGROUND AND AIMS: Primary adenosquamous carcinoma (ASC) is a rare liver malignancy with very little data published so far. We describe the clinical characteristics of this tumor and analyze its survival pattern to improve the diagnosis and treatment. MATERIALS AND METHODS: This study collected data of 15 patients with primary hepatic ASC in our hospital within 10 years (from 2009 to 2018). We analyzed the clinical characteristics, imaging data, treatment, and survival of ASC in the study. Two of these cases have been reported. RESULTS: The common clinical symptoms of hepatic ASC are liver pain and jaundice. Laboratory examination showed that carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) increased, but Alpha-FetoProtein (AFP) did not. Primary hepatic ASC is a rare subtype of intrahepatic cholangiocarcinoma (ICC) and meets the requirements of pathological diagnosis: CK20 (-), CK7 (+), CK19 (+), and p63 (+). Of the 15 patients, 11 were treated surgically, of which 3 patients received adjuvant chemotherapy. The prognosis of ASC patients is poor with a median survival time (MST) of 6 months (range: 2 to 15). The duration of MST in surgically treated patients was longer than that of nonsurgical patients (7.0 months vs. 3.0 months). Patients that received adjuvant chemotherapy survived longer (MST: 15 months). Patients with lymph node metastasis had a worse prognosis. CONCLUSION: Primary hepatic ASC is a rare malignant tumor with a poor prognosis. Radical surgery may be an effective treatment for prolonging survival. Surgical treatment combined with adjuvant therapy may further improve survival.
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The increasingly widespread use of immunohistochemistry and next-generation sequencing (NGS) in the detection of microsatellite instability (MSI) and DNA mismatch repair (MMR) status has led to the observation of various unusual tumour types that exhibit MMR protein deficiency in Lynch syndrome (LS). Here, we report a case of two synchronous colorectal cancer (CRC) tumours simultaneously occurring in a 42-year-old woman with a deleterious germline mutation in MSH6, abundant expression of PD-L1 and high tumour mutation burden (TMB). The two CRC tumours (tumours A and B) harboured highly heterogeneous features. One showed loss of MSH6 protein and a microsatellite stable (MSS)/MSI-low (MSI-L) status, while the other presented no loss of MMR protein and MSI-H status. Furthermore, the 9 common mutated genes between the two CRC tumours had no shared mutation sites. Only 4 KEGG pathways were identified as enriched for five of the common mutated genes, while 8 cancer-related pathways were identified as enriched for 9 and 13 unique mutated genes in tumours A and B, respectively. Therefore, we chose immune checkpoint inhibitors (ICIs) as the potential therapy. This case exemplifies the complexity of tumorigenesis and potential ICI treatment in LS patients.