Abstract 6467: Tumor mutation burden combined with tumor markers as predictive prognostic biomarkers for neoadjuvant chemotherapy in patients with gastric cancer

2020 ◽  
Author(s):  
Yongning Jia ◽  
Honglin Zhu ◽  
Fei Pang ◽  
Fei Shan ◽  
Shuangxi Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Markers ◽  
Prognostic Biomarkers ◽  
Tumor Mutation Burden ◽  
Mutation Burden

scholarly journals Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Nan Zhang ◽  
Peiyu Li ◽  
Xin Wu ◽  
Shaoyou Xia ◽  
Xudong Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Pearson Correlation ◽  
Disease Free Survival ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
D2 Lymph Node Dissection ◽  
Logistic Analysis ◽  
Mutation Burden ◽  
Disease Free

Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.

scholarly journals Prognostic impact of gene copy number instability and tumor mutation burden in patients with resectable gastric cancer

2020 ◽  
Vol 40 (1) ◽  
pp. 63-66
Author(s):  
Lisheng Cai ◽  
Linhai Li ◽  
Dandan Ren ◽  
Xue Song ◽  
Beibei Mao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Prognostic Impact ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Resectable Gastric Cancer

scholarly journals Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Li Zhang ◽  
Yinkui Wang ◽  
Zhongwu Li ◽  
Dongmei Lin ◽  
Yiqiang Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Epstein Barr Virus Infection ◽  
Tumor Mutation Burden ◽  
Barr Virus ◽  
Mutation Burden ◽  
Epstein Barr

Abstract Objectives Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes have unique molecular features that may have different therapeutic methods. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in GC patients. Methods The data of 2504 GC patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed. We analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p = 0.000, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a intestinal group (p = 0.012), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions Using IHC and NGS, MSI status, protein expression, tumor mutation burden (TMB) and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

scholarly journals Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

2020 ◽  
Author(s):  
Li Zhang ◽  
Aiwen Wu ◽  
Zhongwu Li
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
Epstein Barr Virus Infection ◽  
Tumor Mutation Burden ◽  
Barr Virus ◽  
Mutation Burden ◽  
Therapeutic Decisions ◽  
Epstein Barr

Abstract Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

scholarly journals Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

2020 ◽  
Author(s):  
Li Zhang ◽  
Aiwen Wu ◽  
Zhongwu Li
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
Epstein Barr Virus Infection ◽  
Tumor Mutation Burden ◽  
Barr Virus ◽  
Mutation Burden ◽  
Therapeutic Decisions ◽  
Epstein Barr

Abstract Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

scholarly journals Correlation between LRP1B Mutations and Tumor Mutation Burden in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Sizhe Hu ◽  
Xiaokang Zhao ◽  
Feng Qian ◽  
Cancan Jin ◽  
Kaishun Hou
Keyword(s):  
Gastric Cancer ◽  
Mutation Frequency ◽  
Density Lipoprotein ◽  
Roc Curves ◽  
Cancer Prognosis ◽  
Roc Curve Analysis ◽  
Mutation Status ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Relationship

Background. It has been shown that low-density lipoprotein receptor-related protein 1B (LRP1B) mutations correlate with tumor mutation burden (TMB) and prognosis in patients with melanoma and non-small-cell lung cancer, while the relationship between LRP1B mutations and TMB in gastric cancer needs further study. This study is aimed at exploring the relationship between LRP1B mutations and TMB in gastric cancer. Methods. Mutation frequency profiles of the genes in patients with gastric cancer in TCGA-STAD dataset were analyzed by bioinformatics analysis. The relationship among LRP1B mutations, TMB, and patient clinical features in gastric cancer was investigated by the chi-square test. The TMB prediction capacity based on LRP1B mutation status was evaluated by ROC curves. Results. LRP1B is one of the top 10 genes with high gene mutation frequency in gastric cancer. The mutation status of LRP1B in gastric cancer patients was significantly correlated with age and TP53 and MUC16 mutation status. The result of ROC curve analysis revealed that the mutation status of LRP1B could be considered as an indicator of the degree of TMB in patients with gastric cancer. Conclusion. This study presented the relationship between TMB and LRP1B mutations in gastric cancer, providing a novel perspective for gastric cancer prognosis and therapy.

Sign in / Sign up

Export Citation Format

Share Document