Identification of cancer stem cell-related biomarkers in intestinal-type and diffuse-type gastric cancer by stemness ind
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Journal of Translational Medicine Open Access
RESEARCH
Identification of cancer stem cell‑related biomarkers in intestinal‑type and diffuse‑type gastric cancer by stemness index and weighted correlation network analysis Rui Guo1,2,3, Aining Chu1,2,3 and Yuehua Gong1,2,3*
Abstract Background: Cancer stem cells (CSCs) play an important role in drug resistance, recurrence, and metastasis of tumors. Considering the heterogeneity of tumors, this study aimed to explore the key genes regulating stem cells in intestinal-type and diffuse-type gastric cancer. Methods: RNA-seq data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA). WGCNA was used to clustered differentially expressed genes with similar expression profiles to form modules. Furtherly, based on the mRNA expression-based stemness index (mRNAsi), significant modules and key genes were identified. Next, the expression of key genes was further verified by the Oncomine database. Results: MRNAsi scores of GC were significantly higher than that of normal tissue. Additionally, mRNAsi scores of intestinal-type GC (IGC) were significantly higher than that of diffuse-type GC (DGC). WGCNA showed that the blue module of IGC and the brown module of DGC were both the most significantly associated with mRNAsi. We screened out 16 and 43 key genes for IGC and DGC and found that these genes were closely related, respectively. Functional analysis showed the relationship between the key genes confirmed in the Oncomine database and the fate of cells. Conclusions: In this study, 16 and 43 genes related to the characteristics of CSCs were identified in IGC and DGC, respectively. These genes were both associated with cell cycle, which could serve as therapeutic targets for the inhibition of stem cells from both types of GC. Keywords: Diffuse-type gastric cancer, Intestinal-type gastric cancer, Cancer cell stemness, mRNAsi, WGCNA Background As a common neoplasm worldwide, gastric cancer (GC) is the main cause of cancer-related deaths [1]. According to cancer statistics released by the International Agency for Research on Cancer (IARC), there were 952,000 new *Correspondence: [email protected] 1 Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Liaoning Province, The First Hospital of China Medical University, No.155 NanjingBei Street, Heping District, Shenyang 110001, P.R. China Full list of author information is available at the end of the article
cases of GC worldwide in 2012, accounting for 68% of cancer patients, of which 723,000 die, about 88% of all cancer patients [2]. Approximately 90% of GC are adenocarcinoma originated from gastric mucosa. According to the Lauren classification, GC can be separated into the intestinal-type (IGC) and diffuse-type (DGC), which are significantly different in terms of tissue morphology, pathogenesis, biological behavior, prognosis, and survival [3, 4]. Therefore, an in-depth exploration of the molecular characteristics of IGC and DGC is of great significance for clinical dia
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