RESUMO
Gastric cancer is a most malignancy in digestive tract worldwide. This study aimed to investigate the roles of protein arginine methyltransferase 6 (PRMT6) in gastric cancer. Immunohistochemistry was performed to detect PRMT6 expression in gastric tumors. Real-time transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to detected mRNA levels. Protein expression was determined using western blot. Gastric cancer cells were co-cultured with CD8+ T cells. Colony formation assay was performed to detect cell proliferation. Flow cytometry was performed to determine CD8+ T cell function and tumor cell apoptosis. PRMT6 was overexpressed in gastric tumors. High level of PRMT6 predicted poor outcomes of gastric cancer patients and inhibition of CD8+ T cell infiltration. PRMT6 promoted proliferation of CD8+ T cells and enhanced its tumor killing ability. Moreover, PRMT6 upregulated annexin A1 (ANXA1) and promoted ANXA1 protein stability. ANXA1 overexpression suppressed the proliferation of CD8+ T cells and promoted tumor cell survival. PRMT6 functions as an oncogene in gastric cancer. PRMT6-mediated protein stability inhibits the infiltration of CD8+ T cells, resulting in immune evasion of gastric cancer. The PRMT6-ANXA1 may be a promising strategy for gastric cancer.
Assuntos
Anexina A1 , Linfócitos T CD8-Positivos , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteína-Arginina N-Metiltransferases , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Humanos , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Anexina A1/genética , Anexina A1/metabolismo , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Regulação para Cima , Apoptose , Evasão Tumoral/genética , Masculino , Evasão da Resposta Imune , Feminino , Proteínas NuclearesRESUMO
OBJECTIVES: The present study identified the prognostic nutritional factors and their relationships with survival outcome in patients with esophageal cancer treated with chemoradiotherapy (CRT). METHODS: A total of 97 esophageal cancer patients previously treated with CRT were enrolled in the study. The nutritional status was assessed by Nutrition Risk Screening 2002 (NRS-2002). Weight, total serum protein, albumin, prealbumin level, red blood cell, total lymphocyte count, and hemoglobin were also recorded. The prognostic nutritional index (PNI) was calculated. RESULTS: The proportion of patients at nutritional risk from baseline until the sixth week of radiotherapy was increased. In univariate analysis, the NRS-2002 cutoff score ≤3 at baseline was associated with improved 2-year overall survival (OS) than that ≥4. The maximum NRS-2002 cutoff score ≤2 during treatment was associated with an improved 2-year OS that ≥3. The baseline PNI or PNI at the end of CRT ≥45 was associated with improved 2-year OS than that <45. Cox regression analyses revealed that the TNM stage, NRS-2002 score at baseline, and PNI at the third week of CRT were independent risk factors for prognosis. CONCLUSIONS: The NRS2002 scores and PNI are simple and useful markers for predicting the long-term outcome in patients with esophageal cancer after CRT.