MicroRNA-21 (miR-21), Mutant Tumor Protein p53, and Matrix Metalloproteinase-9 (MMP-9) as Risk Markers for High-Grade Tumor Budding (HGTB) in Cervical Carcinoma: A Case-Control Study in a Balinese Population.

OBJECTIVE: High-grade tumor budding (HGTB) is still a controversial parameter in determining the aggressiveness of cervical carcinoma, yet the molecular mechanism of TB is still not comprehensively understood. This study aimed to evaluate whether miR-21, mutant p53, and MMP-9 expression are associated with HGTB in cervical carcinoma. METHODS: This nested case-control study was conducted at the Anatomical Pathology Laboratory of Balimed Denpasar Hospital, Mangusada Badung Hospital, and the Biomolecular Laboratory, Faculty of Medicine and Health Sciences, Warmadewa University, from November 2022 to April 2023. The samples were paraffin blocks from a radical hysterectomy of patients with cervical carcinoma. The expression of miR-21 was examined by real-time quantitative PCR (RT-qPCR), while p53 and MMP-9 were analyzed by immunohistochemistry (IHC). A total of 40 samples were selected using simple random sampling, consisting of 20 low-grade tumor budding (LGTB) samples (controls) and 20 HGTB samples (cases). Data analysis was performed using SPSS version 24. RESULTS: This study found that the risk of HGTB significantly increased in miR-21 overexpression (OR=13.222; 95%CI: 2.790-62.670; p-value<0.001) with sensitivity (SN) 70% and specificity (SP) 85%, high mutant p53 expression (OR=44.333; 95%CI: 4.783-410.943; p-value<0.001) with SN=95% and SP=70%, and high MMP-9 expression (OR=10.524; 95%CI: 2.271-48.757; p-value=0.001) with SN=65% and SP=85%. Multivariate analysis showed a significant independent association between mutant p53 expression (aOR=53.676; 95%CI: 3.844-749.474; p-value = 0.003) and high MMP-9 (aOR=13.355; 95%CI: 1.359-131.237; p-value = 0.026), yet miR-21 did not show a significant result. CONCLUSION: These findings showed a significant relationship between p53 and MMP-9 expression as pro-oncogenic and pro-invasive molecular factors in HGTB cervical carcinoma.