Angiogenesis-related lncRNAs predict the prognosis signature of stomach adenocarcinoma
Authors: Han Chen , Zhang Cong , Wang Huixia , Li Kexin , Zhao Lianmei 
Published: December 2021

Abstract
Background
Stomach adenocarcinoma (STAD), which accounts for approximately 95% of gastric cancer types, is a malignancy cancer with high morbidity and mortality. Tumor angiogenesis plays important roles in the progression and pathogenesis of STAD, in which long noncoding RNAs (lncRNAs) have been verified to be crucial for angiogenesis. Our study sought to construct a prognostic signature of angiogenesis-related lncRNAs (ARLncs) to accurately predict the survival time of STAD.

Methods
The RNA-sequencing dataset and corresponding clinical data of STAD were acquired from The Cancer Genome Atlas (TCGA). ARLnc sets were obtained from the Ensemble genome database and Molecular Signatures Database (MSigDB, Angiogenesis M14493, INTegrin pathway M160). A ARLnc-related prognostic signature was then constructed via univariate Cox and multivariate Cox regression analysis in the training cohort. Survival analysis and Cox regression were performed to assess the performance of the prognostic signature between low- and high-risk groups, which was validated in the validation cohort. Furthermore, a nomogram that combined the clinical pathological characteristics and risk score conducted to predict the overall survival (OS) of STAD. In addition, ARLnc-mRNA coexpression pairs were constructed with Pearson’s correlation analysis and visualized to infer the functional annotation of the ARLncs by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of four ARLncs in STAD and their correlation with the angiogenesis markers, CD34 and CD105, were also validated by RT–qPCR in a clinical cohort.

Results
A prognostic prediction signature including four ARLncs (PVT1, LINC01315, AC245041.1, and AC037198.1) was identified and constructed. The OS of patients in the high-risk group was significantly lower than that of patients in the low-risk group (p < 0.001). The values of the time-dependent area under the curve (AUC) for the ARLnc signature for 1-, 3-, and 5- year OS were 0.683, 0.739, and 0.618 in the training cohort and 0.671, 0.646, and 0.680 in the validation cohort, respectively. Univariate and multivariate Cox regression analyses indicated that the ARLnc signature was an independent prognostic factor for STAD patients (p < 0.001). Furthermore, the nomogram and calibration curve showed accurate prediction of the survival time based on the risk score. In addition, 262 mRNAs were screened for coexpression with four ARLncs, and GO analysis showed that mRNAs were mainly involved in biological processes, including angiogenesis, cell adhesion, wound healing, and extracellular matrix organization. Furthermore, correlation analysis showed that there was a positive correlation between risk score and the expression of the angiogenesis markers, CD34 and CD105, in TCGA datasets and our clinical sample cohort.

Conclusion
Our study constructed a prognostic signature consisting of four ARLnc genes, which was closely related to the survival of STAD patients, showing high efficacy of the prognostic signature. Thus, the present study provided a novel biomarker and promising therapeutic strategy for patients with STAD.