Background Only a small subset of colon cancer patients with mismatch repair deficiency may also benefit from Immune checkpoint inhibitors (ICIs). New biomarkers correlated with ICIs responsiveness need to be explored. Methods The study data were obtained from TCGA, GEO, cBioPortal, UALCAN, UCSC Xena browser, and CPTAC databases. Protein kinase C beta (PRKCB) was screened via weighted gene co-expression network analysis (WGCNA), survival analysis and differential expression analysis. The biological and immune landscape of PRKCB was explored by performing bioinformatics and immunohistochemical analyses. These findings were used to predict responsiveness to immunotherapy. Results Yellow module in WGCNA, as a hub module, was strongly positively correlated with infiltrated CD8 + T cell and Immune Score. PRKCB was an essential member of the yellow module, downregulated in colon cancer tissue, and associated with poor prognosis. GO, KEGG, REACTOME enrichment analysis showed PRKCB was associated with Cytokine-cytokine receptor interaction, Chemokine signaling pathway, T cell receptor signaling pathway, NF-κB signal pathway, Natural killer cell mediated cytotoxicity, and PD-L1 signaling. Meanwhile, the PRKCB expression was highly positively correlated with the infiltration of the CD4 + T cells, CD8 + T cells, and NK cells. Moreover, the immunohistochemistry analysis of tissue microarray demonstrated that PRKCB expression was positively correlated with infiltrated CD8 + T cell and PD-L1 expression. As expected, the TIDE and SubMap algorithm verified that ICIs could be effective in PRKCB-high patients. Conclusion PRKCB-high was associated with good prognoses in colon cancer patients. PRKCB-high was an indicator of inflamed TIME, which correlated with high responsiveness to immunotherapy in colon cancer patients.

Background: WD repeat domain 12 (WDR12) encodes a member of the WD-repeat protein family, a component of a nucleolar protein complex that affects the maturation of the large ribosomal subunit, which was highly expressed in colorectal cancer (CRC) tissues compared to para-cancerous tissues. However, its function is unclear in CRC. Thus, our goal was to reveal the biological role of WDR12 in the tumorigenesis and development of CRC. Method：To investigate the correlation of gene knockdown with CRC malignancy (proliferative and anti-apoptotic) by performing lentivirus-assisted WDR12 knockdown experiments in HCT116 and SW620 model CRC cell lines and Validated in vivo experiments in nude mice. Then the possible mechanism of the downstream pathway of WDR12 was investigated by ingenuity pathway analysis (IPA). Finally, in vitro experiments explored the relationship between RAC1 and WDR12 in cell proliferation and anti-apoptosis. Result: In-vitro lentivirus-assisted WDR12 gene knockdown experiments in CRC cell lines showed cell proliferation inhibition, decreased cell viability, and promotion of cell apoptosis compared to empty controls. Hereafter, In-vivo tumor formation experiments in nude mice revealed that tumor area, volume, and weight were significantly lower for knockdown WDR12. In addition, Ingenuity Pathway Analysis and Western blot showed that knockdown of WDR12 affected the down-regulation of a series of downstream genes, including RAC1, PLK1, EZH2, and SKP2, which affected cell proliferation, apoptosis, and cell cycle. Functional recovery experiments demonstrated that overexpression of RAC1 recovered the ability of WDR12 to promote cell proliferation and inhibit apoptosis. Conclusion: In conclusion, WDR12 may be a novel oncogenic factor and a therapeutic target in CRC. Meanwhile, RAC1 may be one of the interacting genes in the downstream pathway of WDR12.