The expression and clinical significance of motor protein 1 in colorectal cancer and its relationship with autophagy
10.3760/cma.j.cn431274-20230323-00392
- VernacularTitle:发动蛋白1在结直肠癌中的表达和临床意义及其与自噬的关系
- Author:
Jiayuan ZOU
1
;
Yaping YE
Author Information
1. 南方医科大学基础医学院病理学系，广州 510515
- Keywords:
Colorectal neoplasms;
Dynamin 1;
Autophagy
- From:
Journal of Chinese Physician
2023;25(11):1661-1667
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the relationship between the expression of dynamin 1 (DNM1) gene and clinical pathological parameters and prognosis of colorectal cancer (CRC) patients, and explore the association between DNM1 and autophagy mechanisms.Methods:The tumor genome atlas (TCGA) database was used to analyze the mRNA levels of DNM1 in normal intestinal mucosa and cancer tissues of CRC patients, as well as in early [tumor node metastasis (TNM) stage Ⅰ and Ⅱ] and late (TNM stage Ⅲ and Ⅳ) cancer tissues. The Kaplan-Meier method was used to estimate survival time and analyze prognosis; Immunohistochemical staining was used to detect the expression of DNM1 protein in cancer tissues of 118 CRC patients, and the relationship between its expression characteristics, clinical pathological parameters, and prognosis was analyzed; The signal pathways related to DNM1 and autophagy in cancer tissues of (GSEA) CRC patients were analyzed using gene set enrichment; Confocal microscopy was used to detect and analyze the Pearson correlation coefficient (PCC) of DNM1 [along with five other autophagy related proteins Autophagy-related protein 9B (ATG9B), Unc-51 like autophagy activating kinase 1 (ULK1), Beclin1, sequestosome-1 (P62/SQSTM1), Autophagy related 16 like protein1 (ATG16L1)] and the immunofluorescence double staining of microtubule associated protein 1 light chain 3 (LC3).Resultsl:The expression of DNM1 was increased in CRC tumor tissue, and significantly increased in the late stage of the tumor ( P<005); Kaplan-Meier survival analysis showed that the expression level of DNM1 was negatively correlated with tumor prognosis [ HR=1.71, 95% CI (1.21, 2.40), P<0.01]. The positive intensity of DNM1 was related to the depth of tumor infiltration, lymph node metastasis, cancer nodules, distant metastasis, nerve and vascular invasion, degree of differentiation, histological classification, and special histological classification (all P<0.01). The ordered logistic regression model verified that tumor differentiation and the degree of DNM1 positivity were risk factors for poor prognosis in CRC patients, and a strong positive DNM1 was positively correlated with adenocarcinoma recurrence ( P<0.05). The high expression of DNM1 involved negative regulation of key signaling pathways in negative autophagy, such as rapamycin target protein complex 1 (mTORC1), phosphatidylinositol 3 kinase/protein kinase B/rapamycin target protein (PI3K/AKT/mTOR) ( P<0.05, FDR<0.001). Among the six sets of immunofluorescence double staining, the correlation between the expression patterns of DNM1 and LC3B genes was the highest. Conclusions:High expression of DNM1 is a poor prognostic factor for CRC patients, which may be related to tumor progression through positive regulation of autophagy.
