Colorectal cancer (CRC) represents one of the most common malignancies with high morbidity worldwide. RNA methylation (m6A) has been considered to tremendously contribute to cancer initiation and progression since its first discovery. In this study, we comprehensively analyzed associations between mRNA expressions of m6A regulators and CRC tumor samples' epidemiologic information from the Cancer Genome Atlas (TCGA). Multivariate Cox proportional hazard model was applied to screening of m6A regulators whose mRNA expressions were significantly associated with CRC tumor samples' overall survival (OS) probability and those significant regulators were used for LASSO regression analysis to construct CRC prognosis prediction signature. As a result, two regulators i.e., YTHDC2 and ALKBH5 were picked out in multivariate analysis. CRC prognosis signature was constructed based on those two regulators through which CRC tumor samples with favorable and inferior prognosis could definitely be distinguished independent of potential confounding factors. This study should be helpful for identifying prognostic different CRC patients and guiding therapeutic method selection.

The present study aimed to investigate potential prognostic long noncoding RNAs (lncRNAs) associated with colorectal cancer (CRC). An mRNA-seq dataset obtained from The Cancer Genome Atlas was employed to identify the differentially expressed lncRNAs (DELs) between CRC patients with good and poor prognoses. Subsequently, univariate and multivariate Cox regression analyses were conducted to analyze the prognosis-associated lncRNAs among all DELs. In addition, a risk scoring system was developed according to the expression levels of the prognostic lncRNAs, which was then applied to a training set and an independent testing set. Furthermore, the co-expressed genes of prognostic lncRNAs were screened using a Multi-Experiment Matrix online tool for construction of lncRNA-gene networks. Finally, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology (GO) function enrichment analyses were performed on genes in the lncRNA-gene networks using KOBAS, GOATOOLS and ClusterProfiler. The present study identified 82 DELs, of which long intergenic nonprotein coding RNA 2159, RP11-452L6.6, RP11-894P9.1 and RP11-69M1.6, and whey acidic protein four-disulfide core domain 21 (WFDC21P) were reported to be independently associated with the prognosis of patients with CRC. A 5-lncRNA signature-based risk scoring system was developed, which may be used to classify patients into low- and high-risk groups with significantly different recurrence-free survival times in the training and testing sets (P<0.05). Co-expressed genes of WFDC21P or RP11-69M1.6 were utilized to construct the lncRNA-gene networks. Genes in the networks were significantly enriched in ‘tight junction’, ‘focal adhesion’ and ‘regulation of actin cytoskeleton’ pathways, and numerous GO terms associated with ‘reactive oxygen species metabolism’ and ‘nitric oxide metabolism’. The present study proposed a 5-lncRNA signature-based risk scoring system for predicting the prognosis of patients with CRC, and revealed the associated signaling pathways and biological processes. The results of the present study may help improve prognostic evaluation in clinical practice.

Methods S-MK and CEA, related to cancer status, were measured in 106 patients and 30 controls by ELISAs. Diagnostic and Prognostic values of S-MK and CEA for rectal cancer were conducted by receiver operating characteristic (ROC) curves with the analysis of sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) for differential diagnosis. Results Pre-surgical S-MK was elevated in cancer patients than the normal and benign subjects. In term of phases, S-MK and CEA of T3/T4 were both significantly higher than those in T1/T2, with further up-regulation of S-MK. The diagnostic capability of S-MK was higher than CEA and increased in integrating S-MK with CEA when differentiated rectal cancer, benign rectal polyps and normal subjects. Moreover, when evaluating metastasis predictive efficacies, the combination of S-MK and CEA showed higher accuracy than any individual parameter. Conclusions Pre-surgical S-MK is a rectal cancer indicator which is superior to CEA. It can potentially be used to monitor the prognosis of rectal cancer, and predict synchronous metastases, providing assistance to clinicians.

Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing β-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.