Identification of key candidate genes and pathways associated with colorectal aberrant crypt foci-to-adenoma-to-carcinoma progression.

AIM

The present study aimed to detect key candidate genes and pathways involved in colorectal aberrant crypt foci-to-adenoma-to-carcinoma progression.

BACKGROUND

Although colorectal cancer (CRC) is the third most common type of cancer, the involved signaling pathways and driver-genes remain largely unclear. CRC begins with the malignant transformation of precancerous lesions including aberrant crypt foci (ACF) and benign adenomatous polyp or adenoma.

METHODS

A list of formerly reported ACF, adenoma, and CRC-associated proteins was obtained from GeneCards, and then the data in online David Bioinformatics Resources was analyzed. The protein-protein interactions were surveyed utilizing String database and Cytoscape software. After hubs and bottlenecks were recognized, the key genes and pathways were identified through different bioinformatics analysis.

RESULTS

The most important pathways associated with colorectal aberrant crypt foci-to-adenoma progression were attributed to "pathways in cancer" and "chemokine signaling pathway" and those in adenoma-to-carcinoma progression were related to "pathways in cancer," "chemokine signaling pathway," and "Ras signaling pathway." The genes participating in these pathways are key ones. Furthermore, PRKACB, CUL2, and GSK3B were significant as the seed in the clusters related to adenoma and GNB1, RALBP1, ROCK1, and IKBKG in the clusters related to cancer.

CONCLUSION

The key candidate genes and pathways in progress CRC formed precursor lesions were identified by integrated bioinformatics analysis. The results could lead to a better understanding of the cause and underlying molecular events as well as detection of therapeutic targets for CRC.