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

Cai, Lisheng; Li, Linhai; Ren, Dianxu; Xue, Song; Mao, Beibei; Han, Bo; Zhang, Henghui

doi:10.1002/cac2.12007

Cited by 11 publications

(9 citation statements)

References 18 publications

(30 reference statements)

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“…30,31 More specifically, the CNI might be a prognostic biomarker for PDAC. Herein, we found that a low CNI was significantly correlated with a longer PFS ( Figure 3D-F), which was in accordance with previous data showing that a high CNI was associated with worse clinical outcomes in head and neck squamous cell carcinoma (HNSCC), 32 gastric cancer, 33 and PDAC, 34 respectively. Taken together, lower CNI levels might be a strong signature for the identification of PDAC patients who might benefit from adjuvant therapy after pancreatectomy.…”

Section: Discussionsupporting

confidence: 92%

Tumor copy number instability is a significant predictor for late recurrence after radical surgery of pancreatic ductal adenocarcinoma

et al. 2020

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Section: Discussionsupporting

confidence: 92%

Tumor copy number instability is a significant predictor for late recurrence after radical surgery of pancreatic ductal adenocarcinoma

et al. 2020

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“…Genomic profiling research suggests that genomic and epigenomic dysregulation is highly heterogeneous. DNA CNVs exert a vital part in STAD for regulating STAD development; in addition, the resultant transcriptional dysregulation is potentially a driving event during the progression of STAD (Feng et al, 2019;Cai et al, 2020). Besides, research on DNA MET profiling suggests that epigenetic regulation is highly significant in the development of cancer from the points of view of biology and clinic (Choi et al, 2017;Ebrahimi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma

Chen

Liu

et al. 2022

Front. Genet.

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Background: DNA methylation (MET)–mediated transcriptomic disturbance and copy number variations (CNVs) exert a significant influence in stimulating the heterogeneous progression of stomach adenocarcinoma (STAD). Nevertheless, the relation of DNA MET with CNVs, together with its impact on tumor occurrence, is still unclear.Methods: The messenger RNA (mRNA) expression (EXP) profiles, DNA MET, and DNA copy numbers, together with STAD mutation data, were collected from the TCGA official data portal. We employed circular binary segmentation algorithm in “DNAcopy.” library of R package for mapping DNA CNV data at genetic level for all samples based on the segmented CNV data. Stable clusters of samples were recognized using negative matrix factorization cluster analysis based on 50 iterations and the “brunet” method using the MET-correlated (METcor) and CNV-correlated (CNVcor) genes. The R package “iCluster” method was utilized to comprehensively analyze the EXP, MET, and DNA CNV profiles.Results: A total of 313 STAD samples were isolated for checking DNA copy numbers and MET and for measuring EXP. In accordance with our results, we discovered obvious co-regulation of CNVcor genes and METcor counterparts. Apart from that, these genes were subject to multi-omics integration. Meanwhile, three subtypes of STAD were detected and confirmed based on independent data. Among them, the subtype with increased aggressiveness was related to decreased mutation frequencies of ARID1A, PIK3CA, ZFHX3, SPECC1, OBSCN, KMT2D, FSIP2, ZBTB20, TTN, and RANBP2, together with the abnormal levels of JPH3, KCNB1, and PLCXD3.Conclusion: According to the results, these aforementioned genes exerted crucial roles in the development of invasive STAD. Our findings on transcriptomic regulation genomically and epigenetically facilitate the understanding of the STAD pathology from different aspects, which help to develop efficient anti-STAD therapy.

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“…Focusing on gastrointestinal cancer, a study analyzed TMB from targeted NGS data of 40 major genes in 516 patients with resected colorectal cancer and observed that TMB-high (≥ 8 non-synonymous somatic mutations) is associated with better relapse-free survival [10]. In GC, a study including 100 patients used an unknown NGS panel to find that prolonged OS was associated with high TMB (3.72 mutations/Mb) in the discovery set but not in the validation set [11]. Apparently, current results are inconsistent for the prognostic role of TMB in resected tumors, which might be due to different NGS platforms, gene panels, high TMB definitions, tumor types, and others.…”

Section: Introductionmentioning

confidence: 99%

Tumor mutation burden as a biomarker in resected gastric cancer via its association with immune infiltration and hypoxia

Wang

Wang²,

et al. 2021

Gastric Cancer

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Background Tumor mutation burden (TMB) predicts immunotherapy efficacy in solid tumors. However, the biomarker role of TMB is still conflicting in resected tumors. We aimed to examine the association of TMB with prognosis and postoperative chemotherapy (CT) or radiochemotherapy (RCT) efficacy in resected gastric cancer (GC). Methods Whole-exome sequencing (WES) was performed in 73 resected GC specimens. Validation cohorts included 352 patients from The Cancer Genome Atlas (TCGA) and 222 patients from the Asian Cancer Research Group (ACRG). Immune infiltration and hypoxia were evaluated by transcriptome data and immunohistochemistry assay. Results TMB-high GC had favorable overall survival (OS) and disease-free survival (DFS), but the OS and DFS benefits with postoperative CT/RCT were more pronounced in TMB-low GC. These findings were consistent among all three cohorts and were maintained in the pooled cohort. Stratified by stages in the pooled cohort, stage III GC benefited from postoperative CT/RCT regardless of TMB level while stage Ib/II GC benefited from postoperative CT/RCT in TMB-low but not in TMBhigh subgroup. TMB positively correlated with immune infiltration which was characterized by NK cell rather than CD8 + T cell enrichment. TMB-high GC was more hypoxic than TMB-low GC, and TMB-high stage Ib/II GC was the most hypoxic. Conclusions High TMB may predict favorable prognosis in resected GC but poor response to postoperative CT/RCT in stage Ib/II subgroup, which may be determined by TMB-associated immune infiltration and hypoxia, respectively.

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

Cited by 11 publications

References 18 publications

Tumor copy number instability is a significant predictor for late recurrence after radical surgery of pancreatic ductal adenocarcinoma

Tumor copy number instability is a significant predictor for late recurrence after radical surgery of pancreatic ductal adenocarcinoma

Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma

Tumor mutation burden as a biomarker in resected gastric cancer via its association with immune infiltration and hypoxia

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