Abstract
There is a critical requirement for alternative strategies to provide the better treatment in colorectal cancer (CRC). Hence, our goal was to propose novel biomarkers as well as drug candidates for its treatment through differential interactome based drug repositioning. Differentially interacting proteins and their modules were identified, and their prognostic power were estimated through survival analyses. Drug repositioning was carried out for significant target proteins, and candidate drugs were analyzed via in silico molecular docking prior to in vitro cell viability assays in CRC cell lines. Six modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were highlighted considering their prognostic performance. Drug repositioning resulted in eight drugs (abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone). Moreover, significant in vitro inhibition profiles were obtained in abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline (positive control). Our findings may provide new and complementary strategies for the treatment of CRC.
Highlights
Colorectal cancer (CRC) is the most commonly diagnosed cancer in women and men worldwide
Two comprehensive transcriptome datasets associated with colorectal adenomas and tumors were recruited to apply differential interactome methodology for predicting high probability protein-protein interactions (PPIs) in tumor states and identifying differential PPIs
Among the differential PPIs (dPPIs), 718 interactions were repressed and 1707 interactions were activated in the GEO dataset, while 81 interactions were repressed and 1,557 interactions were activated in the TCGA dataset (Figure 1A)
Summary
Colorectal cancer (CRC) is the most commonly diagnosed cancer in women and men worldwide. It occurs in the colon or rectum and affects the large intestine or large bowel. The predicted new cases are over 1, 9 million and the number of deaths is 9,35,000 in 2020 (Sung et al, 2021). It is assumed to increase to 2.2 million new cases and 1.1 million deaths by 2030 (Douaiher et al, 2017). If detected at an early stage, the 5-years survival rate can be as high as 90%. If metastases occur in all parts of the body, the 5-years survival rate drops to 14% (Rahib et al, 2014)
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