Exploring the expression and prognostic utility of NISCH in primary and metastatic rectal cancer

Abstract

Background: Rectal adenocarcinoma (READ) ranks 8th in terms of incidence and 10th in mortality rates, representing a significant public health concern worldwide. As a result, new diagnostic and prognostic biomarkers are urgently needed. NISCH has been identified as both a tumor suppressor and a positive prognostic marker in breast and ovarian cancers. Recent analyses of NISCH across various tumor types have revealed its context-dependent role. However, NISCH has not been extensively studied in READ. The aim of this study was to analyze NISCH expression in both primary and metastatic READ and evaluate its prognostic potential. Material (Patients) and Methods: NISCH levels in normal and READ samples were obtained through Xena Functional Genomics Explorer, TIMER, and GEPIA2 online tools. Additionally NISCH was analysed by RT-qPCR in our two cohorts with paired samples: cohort 1 consisted of 28 patients with primary READ with adjacent normal rectal tissue, and the cohort 2 with 17 patients with rectal cancer with liver metastasis (RCLM) and adjacent normal liver tissue. GAPDH levels were used for normalization. Data were analysed using the 2-dCt method. Kaplan–Meier (KM) analysis was used to evaluate overall survival (OS) and disease-free survival (DFS) in cohort 1 and time to recurrence (TTR) in cohort 2 based on NISCH expression. Results: In silico analyses using Xena and TIMER online tools revealed no significant difference in NISCH expression between READ and normal rectal tissue. In contrast, GEPIA2 analysis indicated that NISCH was reduced in READ. Due to these inconsistent findings across databases, we further evaluated NISCH expression on our cohorts. No significant difference in NISCH expression was observed between READ and adjacent normal rectal tissue in cohort 1. Also, there was no difference in NISCH expression between primary and metastatic READ from cohort 2. However, NISCH was significantly downregulated in RCLM compared to healthy liver tissue. KM analysis showed no association between NISCH expression and OS or DFS (cohort 1) or TTR (cohort 2). Conclusions: While NISCH expression did not differ between primary READ, adjacent normal tissue, or metastatic lesions, it was significantly downregulated in liver metastases compared to healthy liver tissue, suggesting a potential role in the metastatic liver microenvironment. NISCH expression showed no prognostic value for OS, DFS or recurrence in the analyzed rectal cancer cohorts