Affiliation:
1. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
2. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
3. Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China
4. School of Pharmacy, Second Military Medical University, Shanghai 200433, China
Abstract
Several TMED protein family members are overexpressed in malignant tumors and associated with tumor progression. TMED1 belongs to the TMED protein family and is involved in protein vesicular trafficking. However, the expression level and biological role of TMED1 in colorectal cancer (CRC) have yet to be fully elucidated. In this study, the integration of patient survival and multi-omics data (immunohistochemical staining, transcriptomics, and proteomics) revealed that the highly expressed TMED1 was related to the poor prognosis in CRC. Crystal violet staining indicated the cell growth was reduced after knocking down TMED1. Moreover, the flow cytometry results showed that TMED1 knockdown could increase cell apoptosis. The expression of TMED1 was positively correlated with other TMED family members (TMED2, TMED4, TMED9, and TMED10) in CRC, and the protein–protein interaction network suggested its potential impact on immune regulation. Furthermore, TMED1 expression was positively associated with the infiltration levels of regulatory T cells (Tregs), cancer-associated fibroblasts (CAFs), and endothelial cells and negatively correlated with the infiltration levels of CD4+ T cells, CD8+ T cells, and B cells. At last, the CTRP and GDSC datasets on the GSCA platform were used to analyze the relationship between TMED1 expression and drug sensitivity (IC50). The result found that the elevation of TMED1 was positively correlated with IC50 and implied it could increase the drug resistance of cancer cells. This research revealed that TMED1 is a novel prognostic biomarker in CRC and provided a valuable strategy for analyzing potential therapeutic targets of malignant tumors.
Funder
National Natural Science Foundation of China
Oriental Scholars of Shanghai Universities
Jiangxi Province Thousand Talents Program
Young Talent Lifting Project of China Association of Chinese Medicine
Shanghai Rising-Star Program
NATCM’s Project of High-level Construction of Key TCM Disciplines
2021 Shanghai Science and Technology Innovation Action Plan
Three-year Action Plan for Shanghai TCM Development and Inheritance Program
Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine
Innovation team of high-level local universities in Shanghai: Strategic Innovation Team of TCM Chemical Biology