Prognosis‐related gene signature is enriched in cancer‐associated fibroblasts in the stem‐like subtype of gastric cancer

Abstract

related gene signature is enriched in cancer-associated fibroblasts in the stem-like subtype of gastric cancer Dear EditorPrognostic markers in gastric cancer 1 are not only used to clinically classify patients into groups but are also being studied extensively for assessing cancer progression and drug development. Hence, the mechanisms by which genes associated with different prognoses in gastric cancer affect stem-like molecular subtypes require further investigation. We selected the top 500 genes with significantly different prognostic values for stomach adenocarcinoma in The Cancer Genome Atlas (TCGA) (Figure 1A, Table S1). The genes differed significantly between the high and low expression samples (Figure 1B). Most of these 500 genes were enriched during synapse assembly, trans-synaptic signalling, and developmental growth (Figure 1C). The frequency of SIG500 detection in each molecular subtype of gastric cancer was determined, and 99% of the genes were found to be present in the stem-like molecular subtype corresponding to the high group (Figure 1D). The generated Kaplan-Meier plot showed that the group with a high SIG500 score had poor prognosis in three cohorts (Y497, GSE62254 and GSE15459) (Figure 1E). Additionally, we analysed the enriched biological pathways in each cohort in the high SIG500 group. Thus, we observed that in the Yonsei Hospital cohort, 2 biological pathways related to glycerophospholipid biosynthesis were enriched; in the GSE62254 cohort, pathways related to the M phase were enriched, while in the GSE15459 cohort, pathways related to muscle structure development and the NABA core matrix were enriched (Figure 2A). Thirty-two master regulators of cancer, blood vessel morphogenesis, NABA core matrisome, 3 insulin-like growth factor (IGF) transport, and uptake by IGF binding proteins were enriched in SIG500 genes (Figure 2B). Reportedly, signalling pathways that drive epithelial to mesenchymal transition (EMT) and the IGF1/IGF1 receptor pathway are substantiallyThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Gene signature related to cancer stem cells and fibroblasts of stem‐like gastric cancer predicts immunotherapy response

“…In cohort 2, the stem-like signature was enriched in fibroblasts (Figure 1C). 3 We confirmed that 14 pathways were highly upregulated in stem-like tumour cells (Figure 1D). Furthermore, we identified differentially expressed genes (DEGs) by distinguishing tumour cells with highly stem-like signatures from others, as well as the most significantly enriched pathways: blood vessel development and NABA core matrix signalling (Figure 1E).…”

Integrated single-cell and bulk RNA sequencing analysis identifies a cancer-associated fibroblast-related gene signature for predicting survival and therapy in gastric cancer

“…We observed that the higher the abundance of fibroblasts was, the poorer the survival of patients with GC. The reason for this may be that the dense ECM forms a physical barrier that promotes tumor progression and prevents drug penetration [ 28 ]. As with the results of our analysis, fibroblast content can be utilized to predict prognosis, which has been validated in numerous tumors [ 29 – 33 ].…”

Machine Learning Predictor of Immune Checkpoint Blockade Response in Gastric Cancer

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