Copyright
©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
ARTICLE HIGHLIGHTS
Research background
Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and high mortality. Therefore, there is an urgent need to explore biomarkers for the early diagnosis, prognostic assessment and treatment of HCC in the clinic.
Research motivation
Spindle and kinetochore-associated protein 3 (SKA3) is a malignancy-related gene, and plays an important role in promoting the proliferation and migration of tumors. Studies have reported that SKA3 overexpression is significantly associated with poor prognosis in various malignant tumors. However, the mechanism of SKA3 in HCC has not been fully elucidated.
Research objectives
This study aimed to explore the molecular mechanisms of SKA3 in HCC.
Research methods
SKA3 expression, clinicopathological characteristics, and survival analysis were performed using the Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas and Gene Expression Omnibus databases, and the results were further verified with collected clinical samples by western blot and immunohistochemistry staining. Gene Set Enrichment Analysis (GSEA) was performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC. In addition, we utilized the TIMER and single-sample GSEA algorithms to estimate the abundances of tumor-infiltrating immune cells in HCC. The R package "pRRophetic" was applied to predict chemotherapeutic response in HCC patients.
Research results
SKA3 was significantly upregulated in HCC, and upregulated SKA3 expression correlated with poor prognosis in HCC patients. Multivariable COX regression analysis indicated that SKA3 was an independent risk factor for overall survival. GSEA revealed that SKA3 may be involved in proliferation-related processes by regulating cell cycle and DNA repair. In addition, there were lower levels of infiltrating CD8+ T cells, natural killer cells, and dendritic cells in the high SKA3 expression group. Drug sensitivity analysis showed that patients with high SKA3 expression were more sensitive to sorafenib, sunitinib, paclitaxel, doxorubicin, gemcitabine, and vx-680.
Research conclusions
High SKA3 expression was associated with poor prognosis and decreased immune cell infiltration in HCC.
Research perspectives
SKA3 may be a biomarker of poor prognosis and a therapeutic target in HCC.
