Prognostic Immunity and Therapeutic Sensitivity Analyses Based on Differential Genomic Instability-Associated LncRNAs in Left- and Right-Sided Colon Adenocarcinoma

Abstract

Background: The purpose of our study was to develop a prognostic risk model based on differential genomic instability-associated (DGIA) long non-coding RNAs (lncRNAs) of left-sided and right-sided colon cancers (LCCs and RCCs); therefore, the prognostic key lncRNAs could be identified.Methods: We adopted two independent gene datasets, corresponding somatic mutation and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Identification of differential DGIA lncRNAs from LCCs and RCCs was conducted with the appliance of “Limma” analysis. Then, we screened out key lncRNAs based on univariate and multivariate Cox proportional hazard regression analysis. Meanwhile, DGIA lncRNAs related prognostic model (DRPM) was established. We employed the DRPM in the model group and internal verification group from TCGA for the purpose of risk grouping and accuracy verification of DRPM. We also verified the accuracy of key lncRNAs with GEO data. Finally, the differences of immune infiltration, functional pathways, and therapeutic sensitivities were analyzed within different risk groups.Results: A total of 123 DGIA lncRNAs were screened out by differential expression analysis. We obtained six DGIA lncRNAs by the construction of DRPM, including AC004009.1, AP003555.2, BOLA3-AS1, NKILA, LINC00543, and UCA1. After the risk grouping by these DGIA lncRNAs, we found the prognosis of the high-risk group (HRG) was significantly worse than that in the low-risk group (LRG) (all p < 0.05). In all TCGA samples and model group, the expression of CD8+ T cells in HRG was lower than that in LRG (all p < 0.05). The functional analysis indicated that there was significant upregulation with regard to pathways related to both genetic instability and immunity in LRG, including cytosolic DNA sensing pathway, response to double-strand RNA, RIG-Ⅰ like receptor signaling pathway, and Toll-like receptor signaling pathway. Finally, we analyzed the difference and significance of key DGIA lncRNAs and risk groups in multiple therapeutic sensitivities.Conclusion: Through the analysis of the DGIA lncRNAs between LCCs and RCCs, we identified six key DGIA lncRNAs. They can not only predict the prognostic risk of patients but also serve as biomarkers for evaluating the differences of genetic instability, immune infiltration, and therapeutic sensitivity.

Identification of an m6A-Related Long Noncoding RNA Risk Model for Predicting Prognosis and Directing Treatments in Patients With Colon Adenocarcinoma

“…Our study identified 29 prognosis-associated, m6A-related lncRNAs based on data from 379 COAD patients, and 12 of them were used to construct the m6A-LPS. NKILA and BOLA3-AS1 have been identified as unfavorable factors for colon cancer (Xu et al, 2021a;Guo et al, 2021;Chen et al, 2022;Qiu et al, 2022), which is consistent with the findings of this study. PCED1B-AS1 was reported to promote the proliferation of COAD by regulating the miR-633/HOXA9 axis, which was proven by in vitro and in vivo experiments (Liu et al, 2022).…”

Significance of platelet adhesion-related genes in colon cancer based on non-negative matrix factorization-based clustering algorithm

“…Four lncRNAs (ARRDC1-AS1, OIP5-AS1, BOLA3-AS1, and NIFK-AS1) were mentioned in previous COAD studies. 59 – 62 Collectively, these factors may lead to the further exploration of COAD progression and can be investigated as biomarkers and therapeutic targets for COAD.…”

N1-Methyladenosine-Related lncRNAs Are Potential Biomarkers for Predicting Prognosis and Immune Response in Uterine Corpus Endometrial Carcinoma

“…Researchers once constructed a signature that had the prognosis ability of UCEC in light of five glycolysis-related lncRNAs, including BOLA3-AS1 [37]. BOLA3-AS1 could also participate in the construction of models to predict the prognosis of gastric cancer, as well as left-sided and right-sided colon cancers [79,80]. AC006329.1 has great potential for assessing risk and supplying personal treatment for colon cancer patients [81].…”