Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 26, 2022; 10(9): 2783-2791
Published online Mar 26, 2022. doi: 10.12998/wjcc.v10.i9.2783
Overexpression of Ubiquilin4 is associated with poor prognosis in patients with cervical cancer
Li-Na Wang, Ke-Jin Huang, Le Wang, Hai-Yan Cheng
Li-Na Wang, Ke-Jin Huang, Le Wang, Hai-Yan Cheng, Department of Gynaecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
Author contributions: Cheng HY created the initial concept and study design; Wang LN and Huang KJ were responsible for data collection and verification of the raw data; Wang LN and Wang L did statistical analyses; Cheng HY, Huang KJ, and Wang LN interpreted the data; Cheng HY, Huang KJ, Wang LN, and Wang L were involved in writing the manuscript and the decision to submit for publication;all authors read and approved the final manuscript.
Institutional review board statement: All procedures in this study were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Hai-Yan Cheng, MD, Doctor, Department of Gynaecology Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, Heilongjiang Province, China. chenghaiyan1900@126.com
Received: November 5, 2021
Peer-review started: November 5, 2021
First decision: January 11, 2022
Revised: January 26, 2022
Accepted: February 15, 2022
Article in press: February 15, 2022
Published online: March 26, 2022
Processing time: 137 Days and 4.6 Hours
Abstract
BACKGROUND

Ubiquilins (UBQLNs) are important factors for cell proteostasis maintenance. UBQLNs are involved in the modulation of the cell cycle, as well as in apoptosis, membrane receptors regulation, DNA repair, epithelial-mesenchymal transition, and miRNA activities. They also affect the selection of double-strand break repair pathways. Abnormal UBQLNs expression can lead to many diseases, including cancer. Studies have found that the expression of Ubiquilin4 (UBQLN4) is associated with the development of several tumor types. However, the association between UBQLN4 and cervical cancer has not been examined yet.

AIM

To investigate the expression of UBQLN4 in cervical cancer and to evaluate its correlation with disease prognosis.

METHODS

Immunohistochemistry was performed to examine the expression of UBQLN4 in 117 cervical cancer tissues and 32 matching pericervical tissues. Paired t-test (two-tailed) was used to compare the differences between groups. We collected patients’ clinical characteristics, including age, histological grade, pathologic type, lymph node metastasis, and FIGO stage (2018) and compared them by chi-square test. All patients were followed for 5.5 to 6.8 years. Kaplan-Meier method and log-rank test were used to compare the differences in the overall survival (OS) and progression-free survival (PFS) among the different groups.

RESULTS

Overexpression of UBQLN4 was observed in 70.9% (83/117) of all cervical cancer tissues and in 15.6% (5/32) of the paired parauterine tissues. The expression of UBQLN4 was associated with lymph node metastasis, poor differentiation, and advanced stage, but the difference was not significant. Kaplan-Meier and log-rank test results suggested the high expression of UBQLN4 was associated with short OS and PFS. Regardless of UBQLN4 expression, the patient age and FIGO stage were also associated with disease prognosis. The statistically significant variables obtained from univariate the Kaplan-Meier analysis were subjected to Cox multivariate survival regression analysis, which showed that, in addition to the FIGO stage and age, UBQLN4 was also an independent prognostic marker for OS and PFS (P = 0.011 and P = 0.024, respectively).

CONCLUSION

The overexpression of UBQLN4 was associated with poor prognosis in cervical cancer. Our study proposed a novel prognostic factor and improved the existing understanding of the pathogenesis of cervical cancer.

Keywords: Cervical cancer; Immunohistochemistry; Prognosis; Ubiquilin4; Overall survival; Progression-free survival

Core Tip: Cervical cancer is the most common malignant tumor in women. At present, the exact molecular mechanism of its occurrence and development mainly focuses on the regulation of gene expression level, while few researches on the regulation of protein level of translation products. Ubiquilin4 (UBQLN4) regulates protein homeostasis in cells through interactions with different products and proteasomal degradation. Studies have found that the expression of UBQLN4 was associated with several tumors. However, the association between UBQLN4 and cervical cancer has not been examined. In this study, we aimed to measure association between UBQLN4 expression and poor prognosis in cervical cancer.