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A Comprehensive Pan-Cancer Analysis of the Potential Biological Functions and Prognosis Values of RICTOR
Ying Sun1,2, Rui Li2, Baoting Nong3
1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Abstract:
The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been recognized for many years. However, the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway has only recently come to light. The function of RICTOR in pan-cancer still needs to be systematically elucidated. In this study, we examined RICTOR's molecular characteristics and clinical prognostic value by pan-cancer analysis. Our findings indicate that RICTOR was overexpressed in twelve cancer types, and a high RICTOR expression was linked to poor overall survival. Moreover, the CRISPR Achilles' knockout analysis revealed that RICTOR was a critical gene for the survival of many tumor cells. Function analysis revealed that RICTOR-related genes were mainly involved in TOR signaling and cell growth. We further demonstrated that the RICTOR expression was significantly influenced by genetic alteration and DNA-methylation in multiple cancer types. Additionally, we found a positive relationship between RICTOR expression and the immune infiltration of macrophages and cancer-associated fibroblasts in Colon adenocarcinoma and Head and Neck squamous cell carcinoma. Finally, we validated the ability of RICTOR in sustaining tumor growth and invasion in the Hela cell line using cell-cycle analysis, the cell proliferation assay, and wound-healing assay. Our pan-cancer analysis highlights the critical role of RICTOR in tumor progression and its potential as a prognostic marker for various cancer types.
Insights
Rapamycin-insensitive companion of mTOR (RICTOR) is crucial for tumor cell survival and progression across many cancers. High RICTOR expression correlates with poor survival, highlighting its potential as a prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is vital in cancer.
- The role of RICTOR (rapamycin-insensitive companion of mTOR) within this pathway is increasingly recognized but requires further pan-cancer investigation.
Purpose of the Study:
- To systematically elucidate the molecular characteristics and clinical prognostic value of RICTOR across various cancer types.
- To investigate RICTOR's dependency in tumor cells and its relationship with genetic alterations and immune microenvironment.
Main Methods:
- Pan-cancer analysis of RICTOR expression and its correlation with overall survival.
- CRISPR Achilles' knockout screening to assess RICTOR's essentiality for tumor cell survival.
- Analysis of RICTOR's association with genetic alterations, DNA methylation, and immune cell infiltration.
- In vitro validation using cell-cycle, proliferation, and wound-healing assays in HeLa cells.
Main Results:
- RICTOR was overexpressed in twelve cancer types, with high expression linked to poorer overall survival.
- RICTOR was identified as a critical gene for tumor cell survival.
- RICTOR expression is influenced by genetic alterations and DNA methylation.
- RICTOR expression positively correlated with macrophage and cancer-associated fibroblast infiltration in specific cancers.
- RICTOR promotes tumor growth and invasion in vitro.
Conclusions:
- RICTOR plays a critical role in pan-cancer progression.
- RICTOR is a potential prognostic biomarker for various cancer types.
- Targeting RICTOR may offer therapeutic opportunities in cancer treatment.
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