Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion
Ming-Yue Tang, Xue Shen, Run-Sheng Yuan, Hui-Yuan Li, Xin-Wei Li, Yi-Ming Jing, Yue Zhang, Hong-Hong Shen, Zi-Shu Wang, Lei Zhou, Yun-Chuan Yang, He-Xin Wen, Fang Su
Ming-Yue Tang, Xue Shen, Hui-Yuan Li, Xin-Wei Li, Yue Zhang, Hong-Hong Shen, Zi-Shu Wang, Fang Su, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
Run-Sheng Yuan, Otolaryngology and Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
Yi-Ming Jing, Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
Lei Zhou, Yun-Chuan Yang, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
He-Xin Wen, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
Author contributions: Tang MY, Shen X, Yuan RS, and Su F designed the study and wrote the manuscript; Tang MY, Li HY, and Li XW completed the experiments; Tang MY, Jing YM, Zhang Y, and Shen HH analyzed the collected data; Zhou L and Yang YC provided the hepatocellular carcinoma surgical samples; Tang MY, Wang ZS, and Wen HX were responsible for the literature search to improve the work and revise the manuscript; and all the authors reviewed the manuscript and approved its publication.
Supported by the Anhui Provincial Health Scientific Research Project Provincial Financial Support Key Project, No. AHWJ2023A10110; College Teaching Quality Engineering Project of Anhui Educational Committee, No. 2021jyxm0954; and College Student Innovation Training Program of Bengbu Medical College, No. Byycxz22110.
Institutional review board statement: The study was reviewed and approved by the Bengbu Medical University Institutional Review Board [approval No. (2023)330].
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Bengbu Medical University Institutional Review Board [approval No. (2023)149].
Conflict-of-interest statement: The authors have no relevant financial or nonfinancial interests to disclose.
Data sharing statement: The original data contributed to the study are included in the article/supplementary material, and further inquiries can be directed to the corresponding authors.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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: Fang Su, Doctor, Academic Research, Doctor, Researcher, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Longzihu District, Bengbu 233000, Anhui Province, China. sufang2899@163.com
Received: December 10, 2023
Peer-review started: December 10, 2023
First decision: January 5, 2024
Revised: January 17, 2024
Accepted: February 22, 2024
Article in press: February 22, 2024
Published online: May 15, 2024
Processing time: 151 Days and 3.8 Hours
BACKGROUND
For the first time, we investigated the oncological role of plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7 (TEM7), in hepatocellular carcinoma (HCC).
AIM
To investigate the oncological profile of PLXDC1 in HCC.
METHODS
Based on The Cancer Genome Atlas database, we analyzed the expression of PLXDC1 in HCC. Using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, we validated our results. The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features, such as patient survival, methylation level, tumor immune microenvironment features, and immune cell surface checkpoint expression. Finally, to assess the immune evasion potential of PLXDC1 in HCC, we used the tumor immune dysfunction and exclusion (TIDE) website and immunohistochemical staining assays.
RESULTS
Based on immunohistochemistry, qRT-PCR, and Western blot assays, overexpression of PLXDC1 in HCC was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and PLXDC1-related risk scores were also associated with a poor prognosis.
CONCLUSION
As a result of this study analyzing PLXDC1 from multiple biological perspectives, it was revealed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.
Core Tip: Based on immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot assays, overexpression of plexin domain-containing 1 (PLXDC1) in hepatocellular carcinoma (HCC) was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and tumor immune dysfunction and exclusion assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and PLXDC1-related risk scores were also associated with a poor prognosis.
