Valor prognóstico da expressão de Fosfatidilinositol-3 Quinases Alfa e Gama em pacientes com câncer colorretal

Abstract

Colorectal cancer (CRC) is the third most common cancer in Brazil and develops, in most cases, from benign lesions such as edematous and serrated polyps. It is a multifactorial disease influenced by genetic, environmental, and lifestyle factors, as well as by regulators of cell proliferation, including tumor suppressor genes and oncogenes. Class I phosphatidylinositol-3-kinases (PI3Ks) have been implicated in the pathogenesis of several clinical conditions, including cancer and autoimmune diseases. Thus, the present study evaluated the expression of PI3K alpha and gamma isoforms in patients with colorectal cancer. This was a retrospective, cross-sectional, analytical study that included 72 patients diagnosed with colon and rectal cancer. The inclusion criteria were patients with a histopathological diagnosis of colon and rectal adenocarcinoma from the Haroldo Juaçaba Hospital, Cancer Institute of Ceará. Sociodemographic, clinical, and pathological data were collected. Additionally, the blocked samples were processed for immunofluorescence to quantify PI3Kα and PI3Kγ expression. Statistical analysis was performed using Fisher's test, GraphPad Prism software, version 8.01, and SPSS version 17.0, with significance set at p < 0.05. The results showed that 52.77% of patients were male, with a median age of diagnosis of 60 (55.56%; n=40). Regarding cancer characteristics, statistical significance (p<0.05) was observed for rectal topography (66.67%; n=48; p=0.036). Additionally, 98.6% (n=71) of the tumors were graded as moderately differentiated, and 41.6% (n=30) were clinically staged as II, 25% (n=18) as III, 18.05% (n=13) as I, and 15.28% (n=11) as IV. Distant metastasis was detected in 18% of patients, with the liver being the most common site of metastasis (46.16%; n=6), followed by the lung (15.38%; n=11) and more than one site (38.46%; n=5). Regarding treatment, 84.72% of patients underwent chemotherapy, among which there was a predominance of exclusively adjuvant therapeutic regimens (31.94%, n=23) and the combination of neoadjuvant and adjuvant radiotherapy (31.94%, n=23). Among the patients analyzed, 45.2% died. Regarding the presence of comorbidities and habits, they were diagnosed with hypertension (43.0%; n=31), diabetes (49.1%; n=29; p<0.05), smoking (49.1%; n=29; p=0.05), and alcoholism (41.5%; n=22). In addition, 58.46% of patients had a family history of cancer. It was concluded that increased expression of PI3K alpha and gamma isoforms is associated with rectal CCR, contributing to the worse prognosis of this disease.