Journal of Mazandaran University of Medical Sciences (Oct 2024)
Investigating the Relationship between Changes in the Expression Level of the CLU Gene and the Prognosis of Gastric Cancer Patients
Abstract
Background and purpose: Gastric cancer is one of the most common cancers, with over one million new cases annually, and is the second leading cause of cancer-related deaths worldwide, after lung cancer. This disease is highly heterogeneous, with different primary sites, histological types, molecular classifications, and biological behaviors. The Cancer Genome Atlas has identified four distinct subtypes of gastric adenocarcinoma. In recent decades, various molecular studies have been conducted to understand the mechanisms underlying gastric cancer development and progression, as well as to identify new diagnostic and prognostic biomarkers. Several intracellular processes, including changes in gene expression, can contribute to the development and progression of gastric cancer. Gene expression changes are also implicated in other diseases, such as heart disease, autoimmune disorders, and diabetes. The CLU gene, an evolutionarily conserved gene, encodes the protein clusterin, which plays a role in various cellular processes, including cell-cell adhesion and programmed cell death. Clusterin has multiple roles in carcinogenesis and tumor invasion. This gene is classified as a metastasis suppressor gene, meaning it does not undergo mutations in tumors but is often downregulated in expression. The aim of the current study is to investigate the relationship between changes in CLU gene expression and the prognosis of patients with gastric cancer. Materials and methods: In this cross-sectional study, fifty tumor tissues and adjacent normal tissues were collected from gastric cancer patients. The relative gene expression of CLU was assessed using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). RNA extraction was performed using RNX-plus solution, and cDNA synthesis was carried out using the BIOFACT kit, following the Random Hexamer and oligo(dT) mixed primer method. Gene expression levels were measured using the StepOnePlus thermocycler, with GAPDH serving as the internal control gene. Additionally, a bioinformatics analysis was conducted to evaluate the expression of the CLU gene in two distinct groups of gastric cancer patients. A Kaplan-Meier survival analysis was performed to assess the impact of CLU expression levels on patient survival rates. Furthermore, a comprehensive analysis of CLU expression across multiple types of cancer was conducted using TCGA data. Results: The analysis of CLU gene expression showed that its expression level in tumor samples was 0.46 compared to adjacent normal tissues. Using data from two additional cohorts, we confirmed that CLU gene expression was consistently lower in tumor samples compared to normal samples. At all stages of gastric cancer, CLU expression was significantly reduced compared to adjacent normal tissue. Survival analysis revealed significant differences in overall survival between patients with high CLU expression and those with lower expression. Lower CLU expression was associated with reduced patient survival time. Further analysis showed that in most cancers studied, CLU expression was generally decreased. Conclusion: The expression of the CLU gene can be used as a prognostic marker in gastric cancer, and CLU gene therapy may be considered as a potential treatment option for gastric cancer.
