Dados do Resumo

Título

CD26 and GAPDH induce metastasis in human colorectal cancer

Introdução

CD26 and GAPDH have been reported as markers for colorectal cancer stem cells with tumor-initiating properties and are capable of colorectal cancer (CRC) metastasis. Studies have shown that high CD26 and GAPDH expression and their correlation in CRC specimens are associated with higher TNM staging and are predictors of poor prognosis after resection of CRC. These findings consistently support the low overall survival rate, as well as the high risk of disease progression associated with the presence of CD26+ and GAPDH+ cells.

Objetivo

In this study, we investigated the functional effects and levels of genetic and protein expression of CD26 and GAPDH on CRC metastasis and their association with other tumor-associated biomarkers of progression and proliferation for prognosis impact definition.

Métodos

Seventy-six patients who agreed to provide tumor fragments and tumor-free margins from surgical procedures performed at the Hospital das Clínicas (CAAE 02177612.0.0000.5149) and Hospital da Baleia (CAAE 02177612.0.3001.5091) in Belo Horizonte, MG, diagnosed between 2012 and 2022, were included in the study. Histological slides were prepared and assessed for the quality and availability of the material. For relative quantification, total RNA was extracted, purified, and subjected to integrity analysis. It was transcribed into cDNA and subjected to qPCR for CD26, GAPDH, KI67, E-cadherin, and vimentin; β-actin was the endogenous target of choice. To assess protein abundance, nuclear and cytoplasmic CD26 and GAPDH were analyzed, as well as KI67 and E-cadherin, as they have shown promise in previous analyses. The positive immunolabeling score was determined by the magnitude, intensity, and cell count. Omics data-deposited databases were accessed to evaluate similar patterns observed in other CRC samples and to delineate the possible signaling pathways involved. Finally, the data were correlated with patient and tumor variables to define the prognosis.

Resultados

The high expression of CD26 and GAPDH in tumor samples was notable, as opposed to the low relative expression of both markers in tumor-free samples. When correlated with tumor variables, patients with a high CEA profile, pT3 and pT4 stages, and highly differentiated tumors had a higher quantification of the markers than those diagnosed at pT2. In addition, an increase in Ki67 expression was observed, indicating proliferative behavior and high vimentin expression, which are commonly associated with enabling metastases. In addition, high nuclear CD26 and cytoplasmic GAPDH immunolabeling were observed in patients with advanced disease who had local recurrence and died from the disease. KI67 was highly abundant in tumor samples, especially when CD26 was highly present. To verify the immunoexpression of E-cadherin, which is associated with a favorable prognosis, tumor-negative samples were found to be more abundant than the CRC-positive samples. In silico analyses demonstrated a close relationship between CD26 and GAPDH in CRC and associated their roles in the epithelial-mesenchymal (EMT) transition process.

Conclusões

Our study demonstrated the functional roles of CD26+ and GAPDH+ cells in inducing CRC metastasis and identified their potential involvement in the EMT process, leading to a poor prognosis.

Financiador do resumo

Fundação Oswaldo Cruz; CAPES, FAPEMIG

Palavras Chave

Colorectal cancer; prognosis; biomarkers