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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
High spindle and kinetochore-associated complex subunit-3 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma
Lin-Lin Zheng, Ya-Ru Wang, Zhen-Rong Liu, Zhi-Hao Wang, Chang-Cheng Tao, Yong-Gang Xiao, Kai Zhang, An-Ke Wu, Hai-Yang Li, Jian-Xiong Wu, Ting Xiao, Wei-Qi Rong
Lin-Lin Zheng, Chang-Cheng Tao, An-Ke Wu, Hai-Yang Li, Jian-Xiong Wu, Wei-Qi Rong, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Ya-Ru Wang, Zhen-Rong Liu, Ting Xiao, State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Zhi-Hao Wang, Department of Hepatobiliary Hernia Surgery, Liaocheng Dongcangfu People's Hospital, Liaocheng 252000, Shandong Province, China
Yong-Gang Xiao, The Second Ward of Hepatobiliary Surgery, Qianxinan People's Hospital, Xingyi 562400, Guizhou Province, China
Kai Zhang, Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300000, China
Author contributions: Zheng LL wrote the manuscript; Wang YR, Liu ZR, Wang ZH, Tao CC, Xiao YG, Zhang K, Wu AK and Li HY contributed to the design of and critically reviewed and revised the manuscript; Wu JX, Xiao T and Rong WQ revised the draft; all authors reviewed and approved the final version.
Supported by Beijing Hope Run Special Fund of Cancer Foundation of China, No. LC2020L05.
Institutional review board statement: This study was approved by the Ethics Committee of the Peking Union Medical College Hospital.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors have no conflicts of interest related to the manuscript.
Data sharing statement: Data are available from the corresponding authors upon request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Wei-Qi Rong, MD, Professor, Surgeon, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan South Lane, Beijing 100021, China. dr_rongweiqi@163.com
Received: April 13, 2023
Peer-review started: April 13, 2023
First decision: June 1, 2023
Revised: June 14, 2023
Accepted: July 17, 2023
Article in press: July 17, 2023
Published online: August 27, 2023
Processing time: 134 Days and 0.3 Hours
BACKGROUND
Spindle and kinetochore-associated complex subunit 3 (SKA3) is a malignancy-associated gene that plays a critical role in the regulation of chromosome separation and cell division. However, the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma (HCC) has not been fully elucidated.
AIM
To investigate the molecular mechanisms underlying the role of SKA3 in HCC.
METHODS
SKA3 expression, clinicopathological, and survival analyses were performed using multiple public database platforms, and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples. Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC. Furthermore, the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC. The response to chemotherapeutic drugs was evaluated by the R package “pRRophetic”.
RESULTS
We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC. Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival. GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair. Moreover, patients with high SKA3 expression had significantly decreased ratios of CD8+ T cells, natural killer cells, and dendritic cells. Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib, sunitinib, paclitaxel, doxorubicin, gemcitabine, and vx-680.
CONCLUSION
High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC. SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.
Core Tip: In this research, we used biological methods and bioinformatics analyses to explore the mechanisms underlying hepatocellular carcinoma (HCC) progression. We revealed that upregulated spindle and kinetochore-associated complex subunit 3 (SKA3) was substantially correlated with a poor prognosis in patients with HCC. SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair. Patients in the high SKA3 expression group had significantly decreased ratios of CD8+ T cells, natural killer cells, and dendritic cells. Our study suggested that high SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC. Therefore, SKA3 could serve as a potential biomarker and therapeutic target for HCC.
