Avaliação da expressão do gene TP53 em amostras de pacientes com câncer colorretal e sua correlação com fatores prognósticos

Abstract

Colorectal cancer (CRC) is a neoplasm that affects the large intestine in its segments of the colon, rectum and anus. It is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. Some of the risk factors for colorectal cancer include: high fat diet, sedentary lifestyle, obesity, smoking and excessive alcohol consumption. Among the genes that are frequently mutated, alterations in the TP53 gene are considered one of the main genetic alterations related to the development of CRC. Sociodemographic factors such as ethnicity and socioeconomic status are known to influence the incidence, stage, diagnosis, survival and mortality of this cancer. The aim of this study was to carry out an ambispective cohort study of patients with Colorectal Cancer using paraffin-blocked samples. As well as analyzing TP53 gene expression by real-time PCR in fresh samples from patients at Hospital Napoleão Laureano in João Pessoa/PB, Brazil. Statistical analyzes were performed using SPSS® software, version 22.0 and the public domain program OpenEpi, version 3.01. Association tests were performed, such as Pearson's Chi-square and Fisher's Exact Test, the P value considered statistically significant <0.05. Positive p53 staining was observed in 46.5% of the 43 patient samples analyzed by immunohistochemistry, and 53.5% were negative. Of the samples analyzed for immunohistochemistry, it was found that 55.8% of the patients were female, with a mean age above 60 years (79.1%). The most frequent ethnicity was brown people (81.4%). Regarding the laterality of the tumor, the region of the left colon was more frequent (60.4%), and the most present histological grade was the moderately differentiated (88.3%). As for the morphological pattern, the tubular was the most frequent (74.4%). With regard to Internship, II was the most observed in the study population (81.4%). Metastasis in lymph nodes was absent in most of the individuals analyzed (51.1%). Patients who presented positive marking for carcinoembryonic antigen (CEA) corresponded to 30.2%, considered positive when CEA > 4.0 ng/ml. There was no significant association between p53 expression and any of the analyzed variables (gender, age, education, ethnicity, location, histological grade, histological pattern, stage and positive quantification for CEA). In the analyzes of TP53 gene expression by real-time PCR, performed in fresh samples (n=10), a higher expression of TP53 was observed in normal tissues (adjacent to the tumor) in relation to tumor tissue (p< 0.05 ). The analysis of data from this cohort allowed us to better understand the profile of the disease, highlighting the main sociodemographic and clinical factors associated with the disease, making it possible to assist in possible preventive and management practices for the patient. However, it was not possible to associate p53 expression with other markers such as CEA, or with other pathological clinical factors. More comprehensive studies with a larger number of patients may possibly better clarify the contribution of p53 as a biomarker for colorectal cancer.