Associations of IFT20 and GM130 protein expressions with clinicopathological features and survival of patients with lung adenocarcinoma

Abstract

Background Lung cancer is the leading cause of malignancy-related mortality and lung adenocarcinoma accounts for about 40% of lung malignancies. The aim of this study was to investigate the associations of intraflagellar transport protein 20 (IFT20) and Golgi matrix protein 130 (GM130) expression with clinicopathological features and survival in patients with lung adenocarcinoma. Methods The expressions of IFT20 and GM130 protein in cancerous and matched adjacent lung tissues of 235 patients with lung adenocarcinoma were assessed by tissue microarray and immunohistochemistry, which were indicated by the mean optical density (IOD/area), the rate of positive staining cells and staining intensity score. The correlation between IFT20 and GM130 protein was assessed by Spearman’s rank correlation. Associations of IFT20 and GM130 protein expression with clinicopathological features of patients were analyzed by multivariate logistic regression models. The survival analysis of patients was performed by Cox proportional hazard regression models. Results With adjustment for multiple potential confounders, each one-point increase in IFT20 protein staining intensity score was significantly associated with 32% and 29% reduced risk for TNM stage in II ~ IV and lymphatic metastasis of patients, respectively (P < 0.05). And each one-point increase in GM130 protein staining intensity score was associated with a significant reduction in the risk of poor differentiation and tumors size > 7 cm by 29% and 38% for lung adenocarcinoma patients, respectively (P < 0.05). In stratified Cox model analysis, enhanced IFT20 staining intensity score was significantly decreased the risk of death by 16% for patients without distant metastasis. And elevated the IOD/area of GM130 expression significantly decreased the death risk of lung adenocarcinoma patients with tumor size > 7 cm or distant metastasis by 54% and 65%, respectively (P < 0.05). Conclusion IFT20 and GM130 protein expressions were negatively associated with tumor differentiated types, size, TNM stage and lymphatic metastasis of lung adenocarcinoma. Both IFT20 and GM130 proteins have some protective effects on the survival of lung adenocarcinoma patients with specific clinicopathological features.

IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport

“…In mouse breast cancer cells, IFT20 inhibits epithelial mesenchymal transition and cell migration [ 56 ], while in human osteosarcoma and colorectal cancer cells, it promotes invadopodia formation and tumor invasiveness [ 66 , 67 ]. Interestingly, a positive correlation of IFT20 expression with reduced risk of metastasis and prolonged survival in patients with lung adenocarcinoma associated with specific clinicopathological features has recently been reported [ 99 ]. Thus, even though the role of IFT20 in cancer needs to be explored in more depth, these findings suggest that IFT20 could play important roles also during tumorigenesis.…”

Reevaluating Golgi fragmentation and its implications in wound repair

“…GM130 degradation, mediated by the 26S proteasome, induced GA dispersal and cell death in myeloma cells, indicating a protective role for GM130 in maintaining GA structure (Eisenberg-Lerner et al 2020 ). However, conflicting outcomes were reported, as a clinical study found elevated GM130 expression in lung adenocarcinoma patients, revealing its protective effect on patient survival (Li et al 2022 ). These conflicting reports underscore the complexity of the relationship between GA fragmentation and cellular fate, emphasizing the need for a comprehensive understanding of the changes in GA morphology.…”