Avaliação da expressão gênica de componentes do sistema purinérgico em indivíduos com câncer colorretal

Abstract

Introduction: Colorectal cancer (CRC) is the second most common cancer in women and the third in men, accounting for about 10% of total cancer-related deaths worldwide. Although early-stage CRC patients are often asymptomatic, early diagnosis is crucial to prevent clinical and prognostic deterioration. Screening tests play a fundamental role, along with clinical evaluation, in diagnostic conclusion. As the gold standard, colonoscopy allows for biopsy of premalignant lesions and surgical resection of early-stage adenocarcinomas. In cases of advanced disease, radiotherapy, chemotherapy, and immunotherapy are considered. Research on the relationships between the purinergic system and CRC pathogenesis is emerging. The purinergic system includes extracellular nucleotides and nucleosides, receptors, and enzymes that degrade these nucleotides. Key enzymes include NTPDase (with CD39 being the most relevant), which hydrolyzes ATP to ADP and ADP to AMP; ecto-5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine; and adenosine deaminase, which hydrolyzes adenosine to inosine. The P2X7 receptor, the most studied of the P2 family, has ATP as an agonist and is recognized for its central role in inflammatory processes.Objective: This study aims to analyze the gene expression of ectonucleotidases CD39 and CD73, and the P2X7 receptor in lymphocytes from CRC patients and control individuals. Methodology: This is a cross- sectional study, where patients were selected based on previous contact between the researchers and the Regional Hospital of the West (Chapecó, SC). The study included 13 CRC patients and 11 control individuals. Before the surgical procedure for tumor removal, patients were personally contacted to explain the research, obtain informed consent, and collect 10 ml of blood from each participant. Clinicopathological information from the patients' medical records was also collected to complement the biological analyses. Control individuals were selected based on age and gender matching with the patients. Gene expression data were obtained by RT-qPCR. Results: The relative expression of the P2X7 gene was 1.7 times higher among individuals with CRC compared to the control group (p<0.05). There was no difference in the relative expression of CD39 and CD73 genes between the groups. A positive correlation was found between the relative expressions of CD39 and CD73 genes in both the control group (p<0.001; r=0.9584) and the CRC group (p=0.0027; r=0.7577). Conclusion: The results show that CRC increases the expression of the P2X7 receptor in lymphocytes. It is hoped that this work will contribute to a better understanding of the role of the purinergic system in CRC pathophysiology and encourage more studies related to colorectal carcinogenesis and purinergic signaling.