Abstract
The extracellular matrix (ECM) plays a central role in the formation of the tumor microenvironment. The deposition of the ECM is associated with poor prognosis in a variety of tumors. Aberrant ECM deposition could undermine the effect of chemotherapy and immunotherapy. However, there is no systematic analysis on the relationship between the ECM and prognosis or chemotherapy effect. In the present study, we applied the gene set variation analysis (GSVA) algorithm to score 2199 canonical pathways in 2125 cases of probe or sequencing data and identified the core matrisome as the driving factor in gastric cancer progression. We classified gastric cancer samples into three clusters according to the composition of the ECM and evaluated clinical and multi-omics characterization of ECM phenotypes. The ECM score was evaluated by GSVA score of core matrisome and a higher ECM score predicted poor prognosis of gastric cancer [Hazard Ratio (HR), 2.084; p-value < 2 × 10−16]. In The Cancer Genome Atlas (TCGA) cohort and KUGH, YUSH, and KUCM cohorts, we verified that patients with a low ECM score could benefit from chemotherapy. By contrast, patients with a high ECM score did not achieve satisfactory response from chemotherapy. Determining the characteristics of the ECM microenvironment might help to predict the prognosis and chemotherapy response of patients with gastric cancer, and help to resolve the enigma of chemoresistance acquisition, as well as providing inspiration to develop combination therapy.
Highlights
Gastric cancer (GC) is the third leading cause of cancer-related death and the fifth most common cancer diagnosed worldwide [1]
The Wnt signaling pathway, the common pathway of fibrin clot formation, and autophagy were among the top risk pathways, and the caspase pathway, tumor necrosis factor receptor 1 (TNFR1) pathway, and Fas signaling pathway were among the top favorable pathways (Supplementary Figure S1B)
The extracellular matrix (ECM) score could predict poor prognosis in each stage of gastric cancer. These results suggested that the ECM score could be prognostic factor that is independent of tumor stage in gastric cancer (Supplementary Figures S5A, B)
Summary
Gastric cancer (GC) is the third leading cause of cancer-related death and the fifth most common cancer diagnosed worldwide [1]. Oh et al [8]identified two distinct molecular subtypes: mesenchymal phenotype(MP) and epithelial phenotype (EP) These molecular subtypes show great tumor heterogeneity, distinct clinical outcome and different response to anti-tumor therapy. Cheong et al [11] developed and validated a model with four classifier genes (GZMB, WARS, SFRP4, and CDX1) for predicting adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer. Benefited from these classification and scoring system, the tumor heterogeneity could be defined, evaluated and precisely targeted
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
