Expression of PDZD4 in colorectal cancer and its impact on colorectal cancer progression

Abstract

Background: CRC, as a common malignant tumor of the digestive system, ranks third in terms of incidence and second in terms of mortality among all cancers, representing a significant global public health challenge. PDZ domain-containing protein 4 (PDZD4) has been identified as a reliable biomarker in various tumors, such as hepatocellular carcinoma, but its functional role in CRC remains poorly understood. Methods: Differential expression of PDZD4 in CRC patients was detected through bioinformatics analysis in the TCGA database, and the correlation between PDZD4 and clinical indicators of CRC patients was analyzed in the GSE17536 dataset. Univariate and multivariate COX analysis was performed to verify whether PDZD4 could serve as an independent prognostic factor for CRC. The biological role of PDZD4 in CRC was analyzed through Gene Set Enrichment Analysis (GSEA). The expression differences of PDZD4 in CRC tissues and cells were validated through Immunohistochemical (IHC) analysis and q-PCR. PDZD4 was overexpressed in SW620 and SW480 CRC cell lines, and the transfection efficiency was verified by Western blot and q-PCR. The regulatory effect of PDZD4 on proliferation, migration, and invasion of CRC cells was assessed through CCK-8, wound healing assay, and Transwell assay. Lastly, the regulatory effect of PDZD4 on the PI3K-AKT pathway was examined through Western blot. Results:PDZD4 was significantly downregulated in CRC. Low expression of PDZD4 was positively correlated with poor prognosis and higher clinical stage in CRC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that PDZD4 played multiple biological roles in the progression of CRC. Loss-of-function experiments showed that PDZD4 had significant inhibitory effects on the proliferation, migration, and invasion ability of CRC cell lines in vitro. Western blot experiments indicated that PDZD4 inhibited the PI3K-AKT signaling pathway in CRC cells. Conclusion: PDZD4 can suppress the progression of CRC by inhibiting the PI3K-AKT signaling pathway in CRC cell lines, suggesting the potential of PDZD4 as a new tumor biomarker and therapeutic target in CRC.