Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.

Colorectal cancer (CRC) is one of the most common malignant tumors, with the second-highest mortality of all 36 cancers worldwide. The roles of fatty acid metabolism in CRC were investigated to explore potential therapeutic strategies. The data files were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a prognostic risk score model with fatty acid metabolism-related genes for predicting prognosis in CRC. Patients with a high-risk score had a poorer prognosis in TCGA cohort than those with a low-risk score and were confirmed in the GEO cohort. Further analysis using the “pRRophetic” R package revealed that low-risk patients were more sensitive to 5-fluorouracil. A comprehensive evaluation of the association between prognostic risk score model and tumor microenvironment (TME) characteristics showed that high-risk patients were suitable for activating a type I/II interferon (IFN) response and inflammation-promoting function. Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap algorithm results also demonstrated that high-risk patients are more suitable for anti-CTLA4 immunotherapy. Therefore, the evaluation of the fatty acid metabolism pattern promotes our comprehension of TME infiltration characteristics, thus guiding effective immunotherapy regimens.

BACKGROUND:Increased expression of vimentin in tissue samples from patients with colorectal cancer (CRC) has been previously demonstrated, but its prognostic significance remains controversial, and the clinical significance for patients with stage II...

Colorectal cancer (CRC) is a commonly diagnosed digestive malignancy worldwide. Ras-related protein 1A (RAP1A) is a member of the Ras superfamily of small GTPases and has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in CRC remains unclear. In this study, we firstly analyzed its expression and clinical significance in a retrospective cohort of 144 CRC patients. Then, cellular assays in vitro and in vivo were performed to clarify its biological role in CRC cells. Finally, microarray analysis was utilized to investigate the molecular mechanisms regulated by RAP1A in CRC progression. Firstly, RAP1A expression was abnormally higher in CRC tissues as compared with adjacent normal tissues, and significantly correlated tumor invasion. High RAP1A expression was an independent unfavourable prognostic factor for CRC patients. Combining RAP1A expression and preoperative CEA level contributed to a more accurate prognostic stratification in CRC patients. Secondly, knockdown of RAP1A dramatically inhibited the growth of CRC cells, while it was opposite for RAP1A overexpression. Finally, the microarray analysis revealed RAP1A promoted CRC growth partly through phosphatase and tensin homolog (PTEN)/forkhead box O3(FOXO3)/cyclin D1(CCND1) signaling pathway. FOXO3 overexpression could partly mimic the inhibitory effect of RAP1A knockdown in CRC growth. Moreover, FOXO3 overexpression inhibited CCND1 expression, but had no impact on RAP1A and PTEN expression. RAP1A promotes CRC development partly through PTEN/FOXO3 /CCND1 signaling pathway. It has a great potential to be an effective clinical biomarker and therapeutic target for CRC patients.

High expression of Zinc-finger protein X-linked promotes tumor growth and predicts a poor outcome for stage II/III colorectal cancer patients