Gastric cancer risk-scoring system based on analysis of a competing endogenous RNA network

Abstract

Background Long noncoding RNAs (lncRNAs) can play vital roles in tumor initiation, progression, invasion, and metastasis. However, the functional role of the lncRNA-based competing endogenous RNA (ceRNA) networks in gastric cancer (GC) is still unclear. We aimed to identify novel lncRNAs and their association with GC prognosis. Methods The lncRNA, miRNA, and mRNA expression profiles of GC patients data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified using the edge-R package. Then, the relationship among lncRNAs-miRNAs-mRNAs was integrated into a constructed ceRNA network with Cytoscape software. Using Cox regression analysis, a risk score system based on DEGs associated with patient prognosis in GC was established. Finally, a nomogram was founded to predict the prognosis of GC patients. Results A total of 971 differentially expressed lncRNAs (DElncRNAs), 144 differentially expressed miRNAs (DEmiRNAs) and 2,789 differentially expressed mRNAs (DEmRNAs) were identified and found to be associated with GC risk. Using the bioinformatics method, a ceRNA network involving 62 DElncRNAs, 21 DEmiRNAs and 59 DEmRNAs was constructed. Based on the results of the Cox regression analysis, a risk-scoring system involving 3 lncRNAs (i.e., ADAMTS9-AS1, C15orf54, and AL391152.1) was set up for the survival analysis of GC patients. The area under the receiver operating characteristic (ROC) curve for the risk-scoring system was 0.674, with a C-index of 0.64 [95% confidence interval (CI): 0.59–0.69, P=2.806485e−08]. Univariate and multivariate Cox regression analyses demonstrated that the risk-scoring system was an independent prognostic factor for GC. The risk-scoring system is positively associated with advanced tumor grade. The expression of these 3 lncRNAs were validated in GEPIA database. A nomogram based on these 3 lncRNAs was created to predict the prognosis of GC patients. Conclusions Our study established a novel lncRNA-expression-based ceRNA network and an ADAMTS9-AS1-C15orf54-AL391152.1-based risk-scoring system, which can be used to predict the prognosis of GC patients.

Identification and validation of a novel cellular senescence-related lncRNA prognostic signature for predicting immunotherapy response in stomach adenocarcinoma

“…In gastric cancer, LINC00460 promoted tumor progression by silencing CCNG2 in an EZH2/LSD1-dependent manner ( Yang et al, 2020 ). AL139352.1 and AL121748.1 were reported as risk factors and associated with poor prognosis in gastric cancer ( Liu et al, 2020 ; Lai et al, 2021 ), which is consistent with our findings. Zhang et al (2020) reported that a three-lncRNA signature, including SCAT1, could predict pathological response and outcome for esophageal squamous cell carcinoma patients.…”

“…AC007405.2, AL033527.2, and AC083902.1 were identified for the first time. AL136115.1, AL355574.1, and REPIN1-AS1 were reported as favorable underlying factors for STAD patients ( Chen et al, 2021 ; Zhang et al, 2021 ; Luo et al, 2022 ), while AL391152.1 ( Liu et al, 2020 ), AC005165.1 ( Wang et al, 2022 ), AC104695.3 ( Zhang et al, 2021 ), and AC129507.1 ( Zha et al, 2021 ) were risk lncRNAs for STAD patients, which is consistent with our results. ADAMTS9-AS1 can inhibit apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway and promote bladder cancer progression ( Yang et al, 2021 ) while inhibiting colon cancer cell progression through the Wnt/β-catenin signaling pathway ( Li et al, 2020 ).…”

Noncoding RNAs-mediated overexpression of KIF14 is associated with tumor immune infiltration and unfavorable prognosis in lung adenocarcinoma

“…Through the starBase database, the potential upstream lncRNAs of hsa-miR-101-3p were predicted ( Figure 4B ). According to the ceRNA hypothesis, these lncRNAs were also filtered by the following criteria [ 26 , 27 ]: (i) upregulation patterns in LUAD, (ii) positive correlation with KIF14 expression, (iii) negative correlation with hsa-miR-101-3p expression, (iv) negative correlation with LUAD patients’ prognosis, and (v) significant association with unfavorable prognosis in LUAD patients. According to the results listed in Tables 3 – 5 , GSEC and TYMSOS ( Figure 4B , 4C and 4G – 4L ), which were negatively correlated LUAD patients’ OS, were considered as the two most potential upstream lncRNAs of hsa-miR-101-3p/KIF14 axis in LUAD patients ( Figure 5 ), while SNHG6, HELLPAR, and SNHG1 were excluded ( Supplementary Figure 4 ).…”

Stemness-related gene signature for predicting therapeutic response in patients with esophageal cancer

“…Herein, PRICKLE2-AS1, FAM13A-AS1, and LINC00304 were shown to be downregulated in ESCA tumors, whereas C15orf54 was upregulated (log 2 FC =1.51; q value =0.02). C15orf54 is known to be positively associated with high-grade gastric cancer (50) and indeed, C15orf54 may be a potential biomarker for ESCA prognosis.…”