Comprehensive Analysis of the Prognostic Significance of Hsa-miR-100-5p and Its Related Gene Signature in Stomach Adenocarcinoma.

Gaoming Wang,Miao Hu,Xiaohua Jiang,Renhao Hu,Bo Chen,Ran Cui,Ludi Yang,Yongkun Wang

doi:10.3389/fcell.2021.736274

Abstract

Stomach adenocarcinoma (STAD) is one of the most common cancers in the world. However, the prognosis of STAD remains poor, and the therapeutic effect of chemotherapy and immunotherapy varies from person to person. MicroRNAs (miRNAs) play vital roles in tumor development and metastasis and can be used for cancer diagnosis and prognosis. In this study, hsa-miR-100-5p was identified as the only dysregulated miRNA in STAD samples through an analysis of three miRNA expression matrices. A weighted gene co-expression network analysis (WGCNA) was performed to select hsa-miR-100-5p-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a miR-100-5p-related prognostic signature. Kaplan–Meier analyses, nomograms, and univariate and multivariate Cox regression analyses were used to evaluate the prognostic signature, which was subsequently identified as an independent risk factor for STAD patients. We investigated the tumor immune environment between low- and high-risk groups and found that, among component types, M2 macrophages contributed the most to the difference between these groups. A drug sensitivity analysis suggested that patients with high-risk scores may be more sensitive to docetaxel and cisplatin chemotherapy and that patients in the low-risk group may be more likely to benefit from immunotherapy. Finally, external cohorts were evaluated to validate the robustness of the prognostic signature. In summary, this study may provide new ideas for developing more individualized therapeutic strategies for STAD patients.

Highlights

MATERIALS AND METHODSGastric cancer is the fifth most common cancer and the third most common cause of cancer death in the world (Smyth et al, 2020)
The multivariate analysis revealed that hsa-miR-100-5p expression (HR = 1.11, p = 0.035) was an independent risk factor for the overall survival of stomach adenocarcinoma (STAD) patients (Figure 2C)
Kaplan– Meier curves showed that patients who had high hsa-miR100-5p expression levels exhibited worse overall survival (Figure 2D) and disease-free survival (Figure 2E) than those with low hsa-miR-100-5p expression

Summary

MATERIALS AND METHODS

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death in the world (Smyth et al, 2020). Expressed miRNAs (DEMs) between STAD samples and adjacent normal tissues obtained from TCGA database were screened using the R package “DESeq2” (Love et al, 2014) based on the count matrix with thresholds of |log2FoldChange| > 1.0 and adjusted p-values (padj) < 0.05. To validate the candidate genes as robust hsa-miR-100-5p-related genes, STAD samples with both miRNA and gene expression profiles were assigned into two clusters by employing R package “ConsensusClusterPlus” and were subsequently analyzed using principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) (Dorrity et al, 2020). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed based on the training cohort and hsa-miR-100-5p-related genes through R package “glmnet” (Engebretsen and Bohlin, 2019). The random-effects meta-analysis model was used to calculate a pooled hazard ratio (HR) via the R package “meta.” p < 0.05 was considered statistically significant

RESULTS

DISCUSSION

CONCLUSION