Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis

Abstract

Background Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. Methods Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. Conclusions We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis

“…As follows, several key genes signatures were reported to be involved in GC development and prognosis. Thus, Wang et al reported FN1, COL1A1, INHBA, and CST1 to be associated with worse overall survival in GC [ 9 ], Lu et al found that SPP1 and FN1 were correlated with tumor relapse and poor prognosis [ 10 ], Liu et al identified TIMP1, SPP1, CXCL8, THY1, and COL1A1 genes to be negatively correlated with survival [ 11 ], and Chong et al found FN1, TIMP1, SPP1, APOE, and VCAN genes to be associated with poor overall survival in GC patients [ 12 ]. Although TIMP1 is a tissue inhibitor of metalloproteinases, it may also have MMP-independent functions in solid cancers.…”

General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers

“…The four antioxidant-related genes (CHAC1, GGT5, GPX8, and PXDN) were proposed as gene signatures to predict the prognosis of GC patients [ 36 ]. The five upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) were proposed as potential biomarkers and therapeutic targets for GC treatment [ 37 ]. In addition to mRNA, five miRNAs, including let-7b-5p, miR-140-3p, miR-192-5p, miR-223-3p, and miR-24-3p, were significantly upregulated in the serum of patients with NPC and could be used as potential diagnostic biomarkers of NPC [ 38 ].…”

“…SLC26A9 is a member of the solute-linked carrier 26 (SLC26) anion transporter family and is mainly expressed in epithelial cells. SLC26A9 functions uniquely as a chloride channel with minimal conductance to bicarbonate [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. However, the role of SLC26A9 in cancer has not yet been elucidated.…”

Impact of Cancer Stem Cells on Therapy Resistance in Gastric Cancer

“…HMMR binds to microtubules [124] and it is important for the stabilization of the mitotic spindle in human cells [125]. HMMR is highly expressed in different types of cancer, including in GC [126][127][128][129][130][131], in which it represents the most upregulated gene in tumor tissue with respect to normal gastric tissue (data from the TCGA cohort) [132]. It has been shown that HMMR is critical for the maintenance of human embryonic stem cells [133] and also plays a role in the regulation of CSCs in breast cancer and glioblastoma [134,135].…”

“…In line with this, Zhang and collaborators found that the expression of HMMR is upregulated in gastric oncospheres and in GC cell lines resistant to 5-FU, being its silencing detrimental for the oncospheres and sensitizing GC cell lines and derived xenografts to the drug. Notably, high HMMR expression has been associated with poor outcome in GC patients treated with 5-FU, founding and association with lymph node dissemination, tumor relapse and reduced survival [131,132]. The current knowledge regarding HMMR in GC is very limited, yet it could represent a suitable target to impair gCSCs and chemoresistance.…”