Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and is derived from an accumulation of genetic and epigenetic changes. This study explored potential prognostic markers in CRC via the construction and in-depth analysis of a competing endogenous RNA (ceRNA) network, which was generated through a three-step process. First, we screened candidate hub genes in CRC as the primary gene markers to survey their related regulatory non-coding RNAs, miRNAs. Second, the interacting miRNAs were used to search for associated lncRNAs. Thus, candidate RNAs were first constructed into ceRNA networks based on close associations with miRNAs. Further analysis at the isomiR level was also performed for each miRNA locus to understand the detailed expression patterns of the multiple variants. Finally, RNAs were performed an in-depth analysis of expression correlations, which contributed to further screening and validation of potential RNAs with close correlations to each other. Using this approach, nine hub genes, 13 related miRNAs, and 29 candidate lncRNAs were collected and used to construct the ceRNA network. Further in-depth analysis identified the MFAP5-miR-200b-3p-AC005154.6 axis as a potential prognostic marker in CRC. MFAP5 and miR-200b-3p have previously been reported to play important roles in tumorigenesis. These RNAs showed potential prognostic values, and the combination of them may have more sensitivity than using them alone. In conclusion, MFAP5, miR-200b-3p, and AC005154.6 may have potential prognostic value in CRC and may provide a prognostic reference for this patient population.
Highlights
Colorectal cancer is one of the most common malignancies
Identifying new prognostic biomarkers is essential for Colorectal cancer (CRC), as this contributes to exploring the mechanisms of metastasis and surveying candidate gene targets for therapy
According to the competitive endogenous RNAs (ceRNAs) hypothesis, we proposed an approach to construct a ceRNA network in CRC based on multiple RNA datasets
Summary
Colorectal cancer is one of the most common malignancies. significant advancements have been made in the early diagnosis and treatment of CRC, there remains an increased risk of cancer-related death from CRC in the United States (Rahman et al, 2015; Callahan et al, 2019). The annual rate of new CRC diagnoses is increasing worldwide (Ferlay et al, 2015), but most patients can be treated at early stages (Pawa et al, 2011). Both environmental and genetic factors influence the occurrence and development of cancer. The pathological progression of CRC is a multistep processes that is caused by the accumulation of genetic alterations, primarily gene mutations and epigenetic changes (Worthley et al, 2007). Inflammation is a crucial hallmark of cancer that is caused by multiple factors (Sun and Kato, 2016; Long et al, 2017). Surgery is the main therapy for localized CRC, and adjuvant chemotherapy is used for many patients
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