Identification of ASMTL-AS1 and LINC02604 lncRNAs as novel biomarkers for diagnosis of colorectal cancer.

Abstract

Purpose: Colorectal cancer is one of the major leading causes of death worldwide, and available treatments for advanced colorectal cancer are not successful. Therefore, early detection of colorectal cancer is essential to improve patient survival, and biomarkers are potential tools to achieve this goal. Considering the key role of lncRNAs in cancers, the aim of this study is to identify lncRNAs involved in colorectal cancer as new potential prognosis biomarkers for CRC.

Methods: In this observational study, gene expression data obtained from the TCGA database were analyzed, Identification of differentially expressed mRNAs, miRNAs, and lncRNAs was performed, and ceRNA network was drawn. Also, survival analysis of patients was performed in order to identify potential biomarkers related to the diagnosis and prognosis of colon cancer. After confirming the results using the GSE39582 dataset, the expression of target lncRNAs in colorectal tumor tissues was also investigated to confirm the bioinformatic data.

Results: Analysis of the TCGA data showed that the expression of three lncRNAs-SNHG7, ASMTL-AS1, and LINC02604-that had the highest interaction with other miRNAs and mRNAs identified based on the ceRNA network was increased in colorectal cancer. Also, based on the ceRNA network, three microRNAs, hsa-let-7d-5p, hsa-mir-92a-3p, and hsa-mir-423-5p, and eight mRNAs, including CPA4, MSI2, RRM2, IGF2BP1, ONECUT2, HMGA1, SOX4, and SRM, were associated with all three mentioned lncRNAs, the expression of microRNAs was decreased and the expression of mRNAs was increased. By enrichment analysis, it was found that the target lncRNAs are involved in the processes of cell proliferation, apoptosis, and metastasis, indicating their importance in the development and malignancy of colorectal cancer. Furthermore, Kaplan-Meier analysis showed a significant increase in mortality in patients with higher expression levels of these lncRNAs. Analysis of the GSE39582 dataset, and real-time RT-PCR analysis, confirmed our bioinformatic results. Also, ROC analysis showed that SNHG7 was a relatively good promising biomarker (AUC = 0.73, p value = 0.02), while ASMTL-AS1 (AUC = 0.92, p value < 0.0001) and LINC02604 (AUC = 1.00, p value < 0.0001) emerged as excellent diagnostic biomarkers in colorectal cancer.

Conclusion: It seems that increased expression of lncRNAs ASMTL-AS1 and LINC02604 can serve as molecular biomarkers for CRC, possibly through the sponge hsa-let-7d-5p, hsa-mir-92a-3p, and hsa-mir-423 5p, which increases target mRNAs, which are effective in the carcinogenesis process.