Avaliação e descrição de biomarcadores moleculares na progressão do adenocarcinoma colorretal e do carcinoma de células escamosas de cabeça e pescoço HPV-positivo

Abstract

CD26 and GAPDH have been associated with tumor initiation and the ability to promote metastasis in human colorectal cancer (CRC). Studies have shown that variable levels of CD26 and GAPDH expression are related to more advanced clinical stages and indicate unfavorable prognosis after tumor resection. These results are consistently associated with a low overall survival rate and a high risk of disease progression. In this study, we investigated the functional effects through gene and protein expression levels of CD26 and GAPDH, associated with other biomarkers of tumor progression, to understand their prognostic impact. The study included 76 patients diagnosed between 2012 and 2022, who consented to provide tumor fragments and free margins from elective surgical procedures performed at Hospital das Clínicas and Hospital da Baleia in Belo Horizonte/MG. The targets included CD26, GAPDH, Ki67, vimentin, CXCR4, e-cadherin and tetraspaninCo029 (TSP). Total RNA was extracted, purified, subjected to integrity analysis, and transcribed into cDNA for relative quantification by qPCR. The protein abundance of CD26, GAPDH, and Ki67 was measured in the cell nucleus and cytoplasm based on the magnitude, intensity, and count of positively stained cells. Finally, the findings were correlated with patients' clinical and demographic variables to determine their prognostic value. The results showed high gene expression of CD26 and vimentin in tumor samples compared to that in normal tissue. In addition, the expression of GAPDH was notably lower in RCC than in other enzymes of the glycolytic pathway. Furthermore, transcript expression was associated with advanced clinical stages, lymph node metastases, the presence of unfavorable anatomopathological characteristics from a prognostic point of view, neoadjuvant treatment, the presence of distant metastases, and a family history of cancer. It is also notable that CD26 and GAPDH levels correlate in RCC, as do CD26, Ki67, CXCR4, Ki67, E-cadherin, and TSP levels. High variation in serum CEA levels was frequent in CD26+ and GAPDH+ samples. There was also marked nuclear immunolabeling of CD26 and GAPDH as well as intense Ki67 positivity in the positive RCC samples. Finally, the abundance of CD26 and GAPDH proteins was high in clinical stage III and angiolymphatic infiltration. This study demonstrated, for the first time, the functional role of CD26+ and GAPDH+ cells and their role in the progression of RCC, as well as suggested other markers that may be associated with the same signaling pathway, leading to an unfavorable prognosis.