Abstract
Accumulated evidence supports that long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. Enhancer RNAs (eRNAs), a subtype of lncRNAs, have recently attracted much attention about their roles in carcinogenesis. Colon adenocarcinoma is one of the most commonly diagnosed tumors with unfavorable prognosis. It highlights the great significance of screening and identifying novel biomarkers. More importantly, it remains to be elucidated with respect to the function of eRNAs in colon adenocarcinoma, as is in pan-cancers. The expression of LINC02257 was determined based on the data obtained from The Cancer Genome Atlas (TCGA). Further evaluation was performed on the basis of the following analyses: clinicopathology and survival analysis, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as multi-omics immunotherapy-related analysis and co-expression analysis. The statistical analysis was conducted in R software, and immune cell infiltration of LINC02257 expression in cancers was investigated by using the CIBERSORT algorithm. By large-scale data mining, our study highlighted that a total of 39 eRNA genes were associated with colon adenocarcinoma prognosis, among which 25 eRNAs showed significant associations with their predicted target genes. LINC02257 was identified as the most significant survival-associated eRNA, with DUSP10 as its target gene. Besides, the high expression of LINC02257 in colon adenocarcinoma was more vulnerable to unfavorable prognosis and correlated with various clinical characteristics. GO and KEGG analyses revealed that LINC02257 was closely correlated with extracellular matrix organization via the PI3K-Akt signaling pathway. Besides, LINC02257 expression correlated with a multi-omics analysis of 33 cancer types, such as survival analysis [overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI)] and immunotherapy-related analysis [tumor microenvironment (TME), tumor mutational burden (TMB), and microsatellite instability (MSI)]. Finally, we investigated the co-expression genes of LINC02257 and its potential signaling pathways across different cancer types. LINC02257 is screened and can function as an independent prognostic biomarker through the PI3K-Akt signaling pathway for colon adenocarcinoma. Simultaneously, LINC02257 may be a multifaceted and significant immunotherapy-related eRNA in different cancers.
Highlights
Colorectal cancer (CRC) encompasses cancers of the colon and the rectum, which has been recognized to be one of the most commonly diagnosed gastroenterological malignancies
Two subgroups of high and low expression groups were divided based on the median value of enhancer RNA (eRNA) expression, and 39 eRNA gene expressions were associated with the prognosis of colon adenocarcinoma (Supplementary Table 1, Kaplan–Meier log-rank test, p < 0.05, false discovery rate (FDR)-adjusted p-value < 0.05)
A total of 1,580 eRNAs were successfully obtained from 521 colon cancer samples, of which LINC02257 was found to have the most significant impact on patients’ survival with its corresponding target gene DUSP10, making it our top key eRNA for colon cancer
Summary
Colorectal cancer (CRC) encompasses cancers of the colon and the rectum, which has been recognized to be one of the most commonly diagnosed gastroenterological malignancies. It accounts for the second and third leading cause of cancer-related mortality among males and females worldwide, respectively (Esmaeili et al, 2020; Harada and Morlote, 2020). Colon adenocarcinoma is a malignancy that originates from the intestinal epithelium and has a rapid increase in its incidence. Accumulated evidence supports that frequent postoperative sporadic relapse and/or metastatic recurrence exerts crucial effects on the prognosis of colon adenocarcinoma patients. It is essential to clarify the molecular mechanisms concerning colon carcinogenesis and to explore promising diagnostic and therapeutic biomarkers to improve patients’ prognosis (Vasaikar et al, 2019)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
