Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015)
Támogató: NKFIH
(KDP-2021)
Background Colorectal carcinoma (CRC) has emerged as one of the most widespread cancers
and was the third leading cause of cancer-related mortality in 2020. The role of the
podosomal protein Tks4 in tumor formation and progression is well established, including
its involvement in gastric carcinoma and hepatocellular carcinoma; however, exploration
of Tks4 and its associated EMT-regulating interactome in the context of colon cancer
remains largely unexplored.Methods We conducted a comprehensive bioinformatic analysis
to investigate the mRNA and protein expression levels of Tks4 and its associated partner
molecules (CD2AP, GRB2, WASL, SRC, CTTN, and CAPZA1) across different tumor types.
We quantified the expression levels of Tks4 and its partner molecules using qPCR,
utilizing a TissueScan colon cancer array. We then validated the usefulness of Tks4
and its associated molecules as biomarkers via careful statistical analyses, including
Pearson's correlation analysis, principal component analysis (PCA), multiple logistic
regression, confusion matrix analysis, and ROC analysis.Results Our findings indicate
that the co-expression patterns of the seven examined biomarker candidates better
differentiate between tumor and normal samples compared with the expression levels
of the individual genes. Moreover, variable importance analysis of these seven genes
revealed four core genes that yield consistent results similar to the seven genes.
Thus, these four core genes from the Tks4 interactome hold promise as potential combined
biomarkers for colon adenocarcinoma diagnosis and prognosis.Conclusion Our proposed
biomarker set from the Tks4 interactome shows promising sensitivity and specificity,
aiding in colon cancer prevention and diagnosis.