Novel genomic prognostic factors for nonsurgical esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15589-e15589
Author(s):  
Honghai Dai ◽  
Yang Shao ◽  
Xiaoling Tong ◽  
Xue Wu ◽  
Jiaohui Pang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Alterations ◽  
Disease Stage ◽  
Free Survival ◽  
Male Patients ◽  
The Impact

e15589 Background: Definitive concurrent chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients demonstrated great variations in responses and post-treatment progression inevitably. Methods: To identify prognostic factors that could assist in clinical judgment and make predictions ahead of disease relapse, we performed a targeted next generation sequencing of 416 cancer-related genes on primary tumor biopsies from 47 ESCC patients with locally advanced or metastatic nonsurgical diseases. Patients were subjected to dCRT treatment and local recurrence free survival (LRFS), progression free survival (PFS) and overall survival (OS) times were analyzed. Results: TP53 (78%), NOTCH1 (32%), ARID1A (13%), FAT1 (13%) and CDKN2A (13%) are the most commonly mutated genes in ESCC, while copy number gains are frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%) and YAP1 (11%). Multivariate analysis including clinical variables (age, gender and disease stage) and individual genetic alterations suggested that gender is an independent prognostic factor and male tend to have longer LRFS, PFS and OS after dCRT treatment. In addition, YAP1 amplification likely increased the risk of disease progression and death. To remove the impact of gender on prognosis, gender stratified survival analysis was performed and found that male patients with YAP1 amplification had significantly shorter LRFS (p = 0.002) and OS (p = 0.03), and also demonstrated a certain trend toward a shorter PFS (p = 0.06) than male patients without YAP1 amplification. Conclusions: YAP1 amplification might be a potentially useful biomarker in predicting treatment outcomes and selecting patients with high relapse risk for closely monitoring.

scholarly journals Nomogram based on SIS predicting the survival of non-surgical thoracic esophageal squamous cell carcinoma treated by IMRT

2021 ◽  
Author(s):  
Xingyu Du ◽  
Shuchai Zhu ◽  
Jing Dong ◽  
Ke Yan ◽  
Xiaobin Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Inflammatory Markers ◽  
Progression Free Survival ◽  
Data Set ◽  
Free Survival

Abstract Background: Several inflammatory markers have been reported to be associated with clinical outcomes in patients with esophageal squamous cell carcinoma (ESCC). This study was to evaluate several pre-radiotherapy serum inflammatory indicators, including the neutrophil / lymphocytes ratio (NLR), platelet / lymphocyte (PLR), systemic immune-inflammatory index (SII), systemic inflammation score(SIS), and compare which one has the highest predicted survival value. Finally, combining inflammatory markers with traditional prognostic factors, a new Nomogram model was developed to predict overall survival (OS) and progression-free survival (PFS) for ESCC patients receiving radiotherapy (RT) or chemoradiotherapy (CRT). Methods: This study retrospectively reviewed the data of 245 patients with thoracic esophageal squamous cell carcinoma (ESCC) underwent RT or CRT in the Fourth Hospital of Hebei Medical University from January 2013 to December 2015. The survival differences of these indexes were compared by the Kaplan-Meier method, and the univariate and the multivariate analyses were performed to determine these prognostic factors of overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional hazards regression models were used to create nomogram for OS and PFS.Results: 239 patients met the eligibility criteria. The estimated 1-, 3-, and 5-year OS and PFS rates were 74.6%, 36.8%, 26.5% and 58.4%, 31.3%, 20.5%, respectively, for the whole group. The difference in survival between OS and PFS was significant when univariate analysis were applied based on these inflammation-based measures. Multivariate analysis showed that tumor length, T stage, TNM stage, chemotherapy, SIS were predictive variables for OS and PFS in the multivariate model. The nomogram model established based on multivariate models of training data set had good predictive ability, the unadjusted C-index was 0.701 (95% CI, 0.662– 0.740) and 0.695 (95% CI, 0.656 - 0.734) for OS and PFS. Conclusions: This study show that SIS, as a comprehensive indicator of inflammation and nutrition, had the strongest predictive power for evaluating prognosis. Moreover, our nomogram can accurately predict OS and PFS after treatment and may provide guidance regarding adjuvant therapy and surveillance.

scholarly journals Inhibited MicroRNA-301 Restrains Angiogenesis and Cell Growth in Esophageal Squamous Cell Carcinoma by Elevating PTEN

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bin Wang ◽  
Peiyan Hua ◽  
Ruimin Wang ◽  
Jindong Li ◽  
Guangxin Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Cycle Distribution ◽  
Pten Inhibition ◽  
The Impact

Abstract Objective Esophageal squamous cell carcinoma (ESCC) is featured by early metastasis and late diagnosis. MicroRNA-301 (miR-301) is known to participate in diverse cancers. Nevertheless, effects of miR-301 on ESCC remain unexplored. Thus, we aim to explore the role of miR-301 in ESCC progression. Methods Expression of miR-301 and phosphatase and tensin homologue (PTEN) in ESCC tissues and cell lines was assessed. Next, the screened cells were treated with altered miR-301 or PTEN oligonucleotide and plasmid, and then, the colony formation ability, cell viability, migration, invasion, cell cycle distribution and apoptosis of ESCC cells were assessed. Moreover, tumor growth and microvessel density (MVD) were also assessed, and the targeting relationship between miR-301 and PTEN was affirmed. Results MiR-301 was upregulated, and PTEN was downregulated in ESCC tissues and cells. KYSE30 cells and Eca109 cells were selected for functional assays. In KYSE30 cells, inhibited miR-301 or overexpressed PTEN suppressed cell malignant behaviors, and silenced PTEN eliminated the impact of miR-301 inhibition on ESCC progression. In Eca109 cells, miR-301 overexpression or PTEN inhibition promoted cell malignant behaviors, and PTEN overexpression reversed the effects of miR-301 elevation on ESCC progression. The in vivo assay revealed that miR-301 inhibition or PTEN overexpression repressed ESCC tumor growth and MVD, and miR-301 elevation or PTEN reduction had contrary effects. Moreover, PTEN was targeted by miR-301. Conclusion Taken together, results in our study revealed that miR-301 affected cell growth, metastasis and angiogenesis via regulating PTEN expression in ESCC.

scholarly journals Functional BCL-2 regulatory genetic variants contribute to susceptibility of esophageal squamous cell carcinoma

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Wenting Pan ◽  
Jinyun Yang ◽  
Jinyu Wei ◽  
Hongwei Chen ◽  
Yunxia Ge ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
B Cell Lymphoma ◽  
Chinese Populations ◽  
Cancer Cell Survival ◽  
Independent Case ◽  
The Impact

Abstract B-cell lymphoma-2 (BCL-2) prevents apoptosis and its overexpression could promote cancer cell survival. Multiple functional BCL-2 genetic polymorphisms, such as rs2279115, rs1801018 and rs1564483, have been identified previously and might be involved in cancer development through deregulating BCL-2 expression. Therefore, we examined associations between these three polymorphisms and esophageal squamous cell carcinoma (ESCC) susceptibility as well as its biological function in vivo. Genotypes were determined in two independent case-control sets consisted of 1588 ESCC patients and 1600 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. The impact of the rs2279115 polymorphism on BCL-2 expression was detected using esophagus tissues. Our results demonstrated that the BCL-2 rs2279115 AA genotype was significantly associated with decreased ESCC risk compared with the CC genotype (OR = 0.72, 95% CI = 0.57–0.90, P = 0.005), especially in nonsmokers (OR = 0.42, 95% CI = 0.29–0.59, P = 0.001) or nondrinkers (OR = 0.44, 95% CI = 0.32–0.62, P = 0.002). Genotype-phenotype correlation studies demonstrated that subjects with the rs2279115 CA and AA genotypes had a statistically significant decrease of BCL-2 mRNA expression compared to the CC genotype in both normal and cancerous esophagus tissues. Our results indicate that the BCL-2 rs2279115 polymorphism contributes to ESCC susceptibility in Chinese populations.

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