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RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance
Yang Wang1, Youbang Xie2, Luomeng Qian1
1Department of Cell Biology, School of Medicine, Nankai University, Tianjin, China.
Background:
RAB42 (Ras-related protein 42) is a new small GTPase that controls the vesicular trafficking from endosomes to trans-Golgi network in mammalian cells. However, the role of RAB42 in multiple cancers, especially in liver hepatocellular carcinoma (LIHC), has not been well investigated.
Methods:
A variety of cancer-related databases and online tools, including TCGA, GTEx, TARGET, QUANTISEQ, EPIC, RNAactDrug, CTR-DB, TIMER algorithms and Sangerbox, were applied to explore the correlation of RAB42 expression with prognosis, immune microenvironment, immune regulatory network, RNA modification, pathway activation and drug sensitivity in pan-cancer. The prognostic, immunomodulatory and tumor-promoting effects of RAB42 were verified in various malignancies and determined by a series of in vitro cellular experiments.
Results:
RAB42 is significantly overexpressed in most cancers with advanced pathological stages. Its overexpression is correlated with poor survival in pan-cancer. RAB42 overexpression has a high diagnostic accuracy of various cancers (AUC > 0.80). RAB42 overexpression not only correlates with distinct stromal immune infiltration and level of immune checkpoint molecules, but also associates with weak immune cell infiltration, immunomodulatory genes expression, and immunotherapeutic response to immune checkpoint inhibitors (ICIs). Additionally, RAB42 overexpression correlates with enhanced expression of m6A RNA methylation-related genes (MRGs) and its interactors. Moreover, overexpression of RAB42 serves as a drug-resistant marker to certain chemotherapies and acts as a potential biomarker for LIHC. Notably, RAB42 overexpression or activation promotes the cellular proliferation, migration and invasion of LIHC.
Conclusion:
Overexpressed RAB42 serves as a potential prognostic biomarker and therapeutic target in pan-cancer, especially in LIHC.
Insights
Ras-related protein 42 (RAB42) is overexpressed in most cancers, correlating with poor survival and impacting the immune microenvironment. RAB42 may serve as a prognostic biomarker and therapeutic target, particularly in liver cancer.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Ras-related protein 42 (RAB42) is a small GTPase involved in vesicular trafficking.
- Its role in various cancers, particularly liver hepatocellular carcinoma (LIHC), remains under-investigated.
Purpose of the Study:
- To investigate the role of RAB42 in pan-cancer, focusing on its correlation with prognosis, immune microenvironment, and therapeutic sensitivity.
- To evaluate RAB42 as a potential biomarker for LIHC.
Main Methods:
- Utilized TCGA, GTEx, TARGET, and other databases for pan-cancer analysis.
- Employed bioinformatics tools (e.g., TIMER, Sangerbox) to assess RAB42 expression.
- Conducted in vitro experiments to validate findings.
Main Results:
- RAB42 is overexpressed in advanced-stage cancers, linked to poor prognosis and high diagnostic accuracy.
- RAB42 influences immune cell infiltration, immune checkpoints, and immunotherapeutic response.
- Overexpression correlates with m6A RNA methylation and drug resistance, promoting LIHC progression.
Conclusions:
- Overexpressed RAB42 is a potential prognostic biomarker and therapeutic target across multiple cancers, especially LIHC.
- RAB42's role in cancer progression and immune evasion warrants further investigation.

