An integrative transcriptome analysis reveals potential predictive, prognostic biomarkers and therapeutic targets in colorectal cancer

Abstract

Background A deep understanding of potential molecular biomarkers and therapeutic targets related to the progression of colorectal cancer (CRC) from early stages to metastasis remain mostly undone. Moreover, the regulation and crosstalk among different cancer-driving molecules including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) in the transition from stage I to stage IV remain to be clarified, which is the aim of this study. Methods We carried out two separate differential expression analyses for two different sets of samples (stage-specific samples and tumor/normal samples). Then, by the means of robust dataset analysis we identified distinct lists of differently expressed genes (DEGs) for Robust Rank Aggregation (RRA) and weighted gene co-expression network analysis (WGCNA). Then, comprehensive computational systems biology analyses including mRNA-miRNA-lncRNA regulatory network, survival analysis and machine learning algorithms were also employed to achieve the aim of this study. Finally, we used clinical samples to carry out validation of a potential and novel target in CRC. Results We have identified the most significant stage-specific DEGs by combining distinct results from RRA and WGCNA. After finding stage-specific DEGs, a total number of 37 DEGs were identified to be conserved across all stages of CRC (conserved DEGs). We also found DE-miRNAs and DE-lncRNAs highly associated to these conserved DEGs. Our systems biology approach led to the identification of several potential therapeutic targets, predictive and prognostic biomarkers, of which lncRNA LINC00974 shown as an important and novel biomarker. Conclusions Findings of the present study provide new insight into CRC pathogenesis across all stages, and suggests future assessment of the functional role of lncRNA LINC00974 in the development of CRC.

Novel biomarkers for neoplastic progression from ulcerative colitis to colorectal cancer: a systems biology approach

“…In recent years, finding molecular markers involved in the progression of cancer in humans has created a fascinating yet challenging field of research 31 , 32 . However, there are problems, such as the lack of more in-depth studies comparing precancerous stages to different stages of cancer with healthy subjects 33 .…”

Prognosis and Novel Drug Targets for Key lncRNAs of Epigenetic Modification in Colorectal Cancer

“…According to univariate Cox, LASSO, and multivariate Cox regression analysis, 8 m 5 CRlncRNAs (AC093157.1, LINC00513, AC025171.4, AC090948.2, ZEB1-AS1, AC109449.1, AC009041.3, and LINC02516) were determined to be significant prognostic factors to explore the prognostic function in CRC. In recent years, lncRNAs have been linked to cancer survival and development in many studies [ 27 , 28 ]. And ZEB1-AS1 was found to be a tumor-related lncRNA prognostic factor in CRC [ 29 ].…”

MicroRNA-nanoparticles against cancer: Opportunities and challenges for personalized medicine

“… 54 miR-132 Up Tissue Samadi et al. 55 miR-193a, let-7g Up Serum Cho et al. 56 miR-21-5p Up Serum Fukada et al.…”

“… 54 Moreover, a transcriptome study identified miR-132 as a poor predictor of overall survival in CRC patients. 55 Exosomal miR-193a and let-7g high expression has been correlated with poor prognosis, recurrence, and venous and lymphatic invasion in CRC. 56 A prospective study investigated the changes of miR-21-5p in CRC patients before surgery and 1 and 6 months after surgery showing significantly higher miR-21-5p levels in relapsing plasma patients.…”