miRNA-Based Signature Associated With Tumor Mutational Burden in Colon Adenocarcinoma

Abstract

Colon adenocarcinoma (COAD) is one of the most common malignant tumors. Tumor mutation burden (TMB) has become an independent biomarker for predicting the response to immune checkpoint inhibitors (ICIs). miRNAs play an important role in cancer-related immune regulation. However, the relationship between miRNA expression and TMB in COAD remains unclear. Therefore, the transcriptome profiling data, clinical data, mutation annotation data, and miRNA expression profiles for cases of COAD were downloaded from the TCGA database. Subsequently, 323 COAD cases were randomly divided into training and test sets. The differential expression of miRNAs in the high and low TMB groups in the training set was obtained as a signature using the least absolute shrinkage and selection operator (LASSO) logistic regression and verified in the test set. Based on the LASSO method, principal component analysis (PCA), and ROC, we found that the signature was credible because it can discriminate between high and low TMB levels. In addition, the correlation between the 18-miRNA-based signature and immune checkpoints was performed, followed by qRT-PCR, to measure the relative expression of 18 miRNAs in COAD patients. The miRNA-based model had a strong positive correlation with TMB and a weak positive correlation with CTLA4 and CD274 (PD-L1). However, no correlation was observed between the model and SNCA (PD-1). Finally, enrichment analysis of the 18 miRNAs was performed to explore their biological functions. The results demonstrated that 18 miRNAs were involved in the process of immunity and cancer pathways. In conclusion, the 18-miRNA-based signature can effectively predict and discriminate between the different TMB levels of COAD and provide a guide for its treatment with ICIs.

Clinical Significance of Disulfidptosis-related Genes and Functional Analysis in Gastric Cancer

“…With the emerging appreciation for the significance of ncRNAs, the present studies pay attention to determine the roles of ceRNA in the process of participating tumor initiation and progress 47 . miRNAs play important roles in cancer-related immune regulation whose expression correlates with tumor mutation burden and immune regulation 48 . Meanwhile, lncRNAs can function as competing endogenous RNAs to impair the miRNA inhibition on targeted mRNAs, further regulating gene expression, protein translation and malignant biological properties 49 .…”

Prognostic analysis of hepatocellular carcinoma based on cuproptosis -associated lncRNAs

“…TMB, which quantifies the number of mutations within tumor cells per million base pairs, serves as a critical indicator. A high TMB suggests a multitude of mutations, potentially leading to the generation of novel antigens that can activate the immune response [ 26 ]. TMB levels in HCC patients can significantly vary, indicating diverse disease profiles.…”

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC

“…Due to the complexity and diversity of immune cell functions in the tumor microenvironment (TME) (Xue et al 2021 ), therapeutic strategies that target only specific elements are often ineffective. Our risk score model shows that the high-score group with better prognosis has a greater density of immune cells, especially T cells, B cells, NK cells and macrophages.…”