Downregulation of the Tumor Suppressor P53 Gene associated with the Progression of Clinical Staging and the Incidence of Distant Metastasis in Indonesian Colorectal Cancer

Background/Aims: A genome-wide study identified tumor suppressor P53 (TP53), BRAF, KRAS, COL-3A1, and SOCS-2 as key drivers of tumorigenesis in human colorectal cancers (CRC). We investigated the association between these molecules' expression levels and the progression of clinical stage as well as the occurrence of distant metastasis in CRC. Methods: We recruited adult patients who underwent colonoscopy and had a histologically confirmed diagnosis of CRC. Clinical staging was determined following extensive workups. Immunohistochemistry (IHC) was used to evaluate the expression level of TP53, KRAS, BRAF, COL-3A1 and SOCS-2 in tumor biopsies. Results: The study involved 63 CRC patients, with a distribution across different stages: 1 (1.6%) in stage I, 6 (9.5%) in stage II, 30 (47.6%) in stage III, and 26 (41.3%) in stage IV. The expression level of TP53 gene were inversely correlated with clinical stages (ρ -0.260, p<0.05). Patients with distant metastases had a significantly lower expression of TP53 compared to those without (0.00 [1.00] vs. 1.00 [23.00], p<0.05). Subanalysis of patients with left-sided tumors demonstrates a significantly reduced expression level of TP53 in both lung (0.00 [0.00] vs. 1.00 [5.25], p<0.05) and overall (0.00 [1.00] vs. 1.00 [21.50], p<0.05) metastases. The expression of TP53 was also positively correlated with BRAF, KRAS, COL-3A1, and SOCS-2 (ρ -0.617, p<0.05; ρ -0.272, p<0.05; ρ 0.348, p<0.05; ρ 0.571, p<0.05). Conclusions: TP53 is downregulated in advanced clinical stages and distant metastases, demonstrating its role in aggressive nature of CRC.