RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma
Backgrounds: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of death among all cancers. The Ras-associated binding (Rab) proteins constitute the largest family of the Ras superfamily of small GTPases, which mainly mediate membrane traffick...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.989655/full |
| _version_ | 1811187835228651520 |
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| author | Hao Peng Erwei Zhu Jitao Wang Jitao Wang Xuanlong Du Chonggao Wang Meng Yang Yewei Zhang |
| author_facet | Hao Peng Erwei Zhu Jitao Wang Jitao Wang Xuanlong Du Chonggao Wang Meng Yang Yewei Zhang |
| author_sort | Hao Peng |
| collection | DOAJ |
| description | Backgrounds: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of death among all cancers. The Ras-associated binding (Rab) proteins constitute the largest family of the Ras superfamily of small GTPases, which mainly mediate membrane trafficking processes. RAB6B is a member of Rab GTPases, and it has been found to be dysregulated in various tumors. However, the clinical significance, correlations with immune cells, and stroma infiltration of RAB6B in HCC remain unclear.Methods: RAB6B mRNA and protein expression in HCC were examined using the TIMER, HCCDB, UALCAN, and HPA databases. The genetic alterations of RAB6B were analyzed by cBioPortal and COSMIC databases. The correlations between RAB6B and tumor-infiltrating immune cells and cancer-associated fibroblasts were explored by using TIMER, TISIDB, and GEPIA databases. Co-expression networks of RAB6B were investigated based on LinkedOmics. Drug sensitivity was analyzed through the GDSC and CTRP databases. RAB6B was knocked down with siRNA in HCC cell lines. EdU assay was performed to detect the cell proliferation ability, flow cytometry was used to compare the differences in the ability of apoptosis, and MTT was used to evaluate the drug sensitivity in vitro.Results: RAB6B mRNA and protein expression were upregulated in the HCC tissues. Kaplan–Meier and Cox regression analyses suggested that highly expressed RAB6B was an independent prognostic factor for poor survival in HCC patients. Moreover, we found that RAB6B expression was positively correlated with the infiltration of immune cells in HCC, including some immunosuppressive cells, chemokines, and receptors, meanwhile RAB6B expression was associated with CD8+T cells exhaustion, resulting in an immunosuppressive microenvironment. Additionally, functional enrichment analysis indicated that RAB6B may be involved in ECM remodeling in the TME, and RAB6B expression was positively associated with CAFs infiltration. Furthermore, RAB6B presented a positive association with sensitivity to GDSC and CTRP drugs. RAB6B knockdown inhibited the cell proliferation and promoted apoptosis and sensitivity to cisplatin of HCC cells in vitro.Conclusion: Our study revealed that RAB6B is a potential biomarker for poor prognosis in HCC patients and correlates with the formation of the immunosuppressive microenvironment in HCC. |
| first_indexed | 2024-04-11T14:10:14Z |
| format | Article |
| id | doaj.art-616a9b5258754e25b7efcfc87a002d4f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T14:10:14Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-616a9b5258754e25b7efcfc87a002d4f2022-12-22T04:19:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.989655989655RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinomaHao Peng0Erwei Zhu1Jitao Wang2Jitao Wang3Xuanlong Du4Chonggao Wang5Meng Yang6Yewei Zhang7Medical School, Southeast University, Nanjing, ChinaThe Second People’s Hospital of Lianyungang (The Oncology Hospital of Lianyungang), Lianyungang, ChinaMedical School, Southeast University, Nanjing, ChinaXingtai Institute of Cancer Control, Xingtai People’s Hospital, Xingtai, ChinaMedical School, Southeast University, Nanjing, ChinaMedical School, Southeast University, Nanjing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaHepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackgrounds: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of death among all cancers. The Ras-associated binding (Rab) proteins constitute the largest family of the Ras superfamily of small GTPases, which mainly mediate membrane trafficking processes. RAB6B is a member of Rab GTPases, and it has been found to be dysregulated in various tumors. However, the clinical significance, correlations with immune cells, and stroma infiltration of RAB6B in HCC remain unclear.Methods: RAB6B mRNA and protein expression in HCC were examined using the TIMER, HCCDB, UALCAN, and HPA databases. The genetic alterations of RAB6B were analyzed by cBioPortal and COSMIC databases. The correlations between RAB6B and tumor-infiltrating immune cells and cancer-associated fibroblasts were explored by using TIMER, TISIDB, and GEPIA databases. Co-expression networks of RAB6B were investigated based on LinkedOmics. Drug sensitivity was analyzed through the GDSC and CTRP databases. RAB6B was knocked down with siRNA in HCC cell lines. EdU assay was performed to detect the cell proliferation ability, flow cytometry was used to compare the differences in the ability of apoptosis, and MTT was used to evaluate the drug sensitivity in vitro.Results: RAB6B mRNA and protein expression were upregulated in the HCC tissues. Kaplan–Meier and Cox regression analyses suggested that highly expressed RAB6B was an independent prognostic factor for poor survival in HCC patients. Moreover, we found that RAB6B expression was positively correlated with the infiltration of immune cells in HCC, including some immunosuppressive cells, chemokines, and receptors, meanwhile RAB6B expression was associated with CD8+T cells exhaustion, resulting in an immunosuppressive microenvironment. Additionally, functional enrichment analysis indicated that RAB6B may be involved in ECM remodeling in the TME, and RAB6B expression was positively associated with CAFs infiltration. Furthermore, RAB6B presented a positive association with sensitivity to GDSC and CTRP drugs. RAB6B knockdown inhibited the cell proliferation and promoted apoptosis and sensitivity to cisplatin of HCC cells in vitro.Conclusion: Our study revealed that RAB6B is a potential biomarker for poor prognosis in HCC patients and correlates with the formation of the immunosuppressive microenvironment in HCC.https://www.frontiersin.org/articles/10.3389/fphar.2022.989655/fullHCCimmune infiltrationRAB6BCAFsTME |
| spellingShingle | Hao Peng Erwei Zhu Jitao Wang Jitao Wang Xuanlong Du Chonggao Wang Meng Yang Yewei Zhang RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma Frontiers in Pharmacology HCC immune infiltration RAB6B CAFs TME |
| title | RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma |
| title_full | RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma |
| title_fullStr | RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma |
| title_full_unstemmed | RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma |
| title_short | RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma |
| title_sort | rab6b is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma |
| topic | HCC immune infiltration RAB6B CAFs TME |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.989655/full |
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