Dataset Information

Stromal score as a prognostic factor in primary gastric cancer and close association with tumor immune microenvironment.

ABSTRACT: BACKGROUND:Gastric cancer remains one of the major causes for tumor-related deaths worldwide. Our study aimed to provide an understanding of primary gastric cancer and prompt its clinical diagnosis and treatment. METHODS:We integrated the expression profiles and overall survival information of primary gastric cancer in TCGA and GEO database and estimated the stromal score of each sample by the estimate R package. Stromal score and clinicopathologic characteristics associated with overall survival were analyzed by using Cox regression and the Kaplan-Meier method. Gene set enrichment analysis (GSEA) and KEGG analysis were performed to explore the potential molecular mechanism in TCGA dataset. The relationship between immunotherapy-associated markers or immune cell types and stromal score was explored by using Pearson correlation analysis. RESULTS:A total of 796 samples were collected for the analysis. Patients with stromal score-high showed poor overall survival (P < .01, HR: 1.407, 95% CI: 1.144-1.731) and identified as an independent prognostic factor. KEGG analysis revealed that stromal score actively involved in diverse tumor-associated pathways. GSEA analysis also revealed stromal score associated with diverse immune-related biological processes. Furthermore, stromal score was related with immunotherapy-associated markers and multiple immune cells. CONCLUSION:Our results showed that stromal score could serve as a potential prognostic biomarker in primary gastric cancer and play an important role in the recognition, surveillance, and prognosis of gastric cancer.

SUBMITTER: Mao M

PROVIDER: S-EPMC7367639 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Stromal score as a prognostic factor in primary gastric cancer and close association with tumor immune microenvironment.

Mao Min M Yu Qingliang Q Huang Rongzhi R Lu Yunxin Y Wang Zhen Z Liao Liang L

Cancer medicine 20200520 14

<h4>Background</h4>Gastric cancer remains one of the major causes for tumor-related deaths worldwide. Our study aimed to provide an understanding of primary gastric cancer and prompt its clinical diagnosis and treatment.<h4>Methods</h4>We integrated the expression profiles and overall survival information of primary gastric cancer in TCGA and GEO database and estimated the stromal score of each sample by the estimate R package. Stromal score and clinicopathologic characteristics associated with ...[more]

PMID: 32432377

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Project description:BackgroundAcral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies.MethodsA total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan-Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM.ResultsThe median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25-5.29, p = 0.01; HR = 2.77, 95% CI 1.22-6.28, p = 0.02; HR = 3.43, 95% CI 1.51-7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17-0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38-9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20-0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients.ConclusionsOur study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.

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Dataset Information

Stromal score as a prognostic factor in primary gastric cancer and close association with tumor immune microenvironment.

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Stromal score as a prognostic factor in primary gastric cancer and close association with tumor immune microenvironment.

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