Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 16, 2022; 10(14): 4368-4379
Published online May 16, 2022. doi: 10.12998/wjcc.v10.i14.4368
Clinical and prognostic significance of expression of phosphoglycerate mutase family member 5 and Parkin in advanced colorectal cancer
Can Wu, Ming-Liang Feng, Tai-Wei Jiao, Ming-Jun Sun
Can Wu, Ming-Liang Feng, Tai-Wei Jiao, Ming-Jun Sun, Department of Endoscope, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Wu C and Sun MJ designed the research study; Feng ML and Jiao TW performed the research; Wu C and Feng ML contributed new reagents and analytic tools; Wu C and Jiao TW analyzed the data and wrote the manuscript; Wu C has received research funding; and all authors have read and approved the final manuscript.
Supported by the Natural Science Foundation of Liaoning Province, No. 2019-BS-279.
Institutional review board statement: This study was approved by the Institutional Review Board of The First Affiliated Hospital of China Medical University (No. 2021-68-2).
Clinical trial registration statement: This study is registered at clinical hospital center “The First Hospital Affiliated to China Medical University” trial registry. The registration identification number is No. 2021-68-2.
Informed consent statement: Informed consent statement was waived.
Conflict-of-interest statement: There are no conflict of interest.
Data sharing statement: No additional data are available.
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: Ming-Jun Sun, Doctor, PhD, Chief Physician, Professor, Department of Endoscope, The First Hospital Affiliated to China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning Province, China. sunydyy@163.com
Received: August 2, 2021
Peer-review started: August 2, 2021
First decision: September 4, 2021
Revised: September 17, 2021
Accepted: March 25, 2022
Article in press: March 25, 2022
Published online: May 16, 2022
Processing time: 283 Days and 16.6 Hours
Abstract
BACKGROUND

Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer (CRC) cells. Phosphoglycerate mutase family member 5 (PGAM5) activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy. However, there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients.

AIM

To assess the clinical significance of PGAM5 and Parkin proteins, as biomarkers for diagnosis and prognosis of CRC, by studying their expression in advanced CRC tissues and their association with clinicopathological parameters.

METHODS

The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry. Each case was evaluated by using a combined scoring method based on signal intensity staining (scored 0-3) and the proportion of positively stained cancer cells (scored 0-4). The final staining score was calculated as the intensity score multiplied by the proportion score. Specimens were categorized as either high or low expression according to the Youden index, and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained. Additionally, we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues.

RESULTS

Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues: PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells. PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues. Moreover, reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis.

CONCLUSION

The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers. Parkin may be a potential marker for the survival of CRC patients.

Keywords: Phosphoglycerate mutase family member 5; Parkin, Mitophagy; Colorectal cancer; Diagnostic marker; Cancer prognosis

Core Tip: Drugs targeting mitochondria can induce mitophagy in colorectal cancer (CRC) cells and restrain cancer cells proliferation. Phosphoglycerate mutase family member 5 (PGAM5) can activate PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy. In this study, we explored 100 patients with advanced CRC to assess the expression and clinical potential of PGAM5 and Parkin proteins using immunohistochemistry. We found that both PGAM5 and Parkin protein expression has diagnostic significance for CRC and may become new biomarkers. Meanwhile, PGAM5 protein and mitophagy-related protein Parkin expression were significantly positively correlated and reduced Parkin protein expression was prognostic for shorter survival. Our data provide a promising foundation for increasing the accuracy of clinical judgment.