Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2022; 28(5): 547-569
Published online Feb 7, 2022. doi: 10.3748/wjg.v28.i5.547
Connective tissue growth factor expression hints at aggressive nature of colorectal cancer
Ishrat Parveiz Bhat, Tahseen Bilal Rather, Irfan Maqbool, Gowhar Rashid, Kulsum Akhtar, Gulzar A Bhat, Fazl Q Parray, Besina Syed, Ishrat Younas Khan, Mohsin Kazi, Muhammad D Hussain, Mudassar Syed
Ishrat Parveiz Bhat, Tahseen Bilal Rather, Irfan Maqbool, Gowhar Rashid, Kulsum Akhtar, Gulzar A Bhat, Mudassar Syed, Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India
Fazl Q Parray, Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India
Besina Syed, Ishrat Younas Khan, Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India
Mohsin Kazi, Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia
Muhammad D Hussain, Department of Pharmaceutical and Biomedical Sciences, California Health Sciences University, California, CA 93612, United States
Author contributions: Bhat IP completed the main experimental work, drafted the manuscript and analyzed the data; Rather TB helped in block collection for IHC experiments, revised the manuscript; Maqbool I contributed to experimental work; Rashid G contributed to patient sample collection; Akhtar K contributed to data collection and methodology design; Bhat GA gave directions in data analysis and helped in proofreading; Parray FQ provided access for patient sample and data collection; Syed B was involved in Immunohistochemical analysis of tissue samples; Khan IY contributed in IHC experimental work; Kazi M contributed to manuscript revision and scientific editing; Hussain MD contributed to manuscript language editing and proofreading.
Supported by Sher-I-Kashmir Institute of Medical Sciences, Srinagar Kashmir, India, No. SIMS/DF/17-467-73.
Institutional review board statement: The study was reviewed and approved by the Institutional Ethics committee (IEC), Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
Conflict-of-interest statement: The authors declare no conflicts of interest to state regarding this study.
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: Mudassar Syed, PhD, Full Professor, Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura Srinagar Kashmir, Srinagar 190011, Jammu and Kashmir, India. syed.mudassar@skims.ac.in
Received: July 26, 2021
Peer-review started: July 26, 2021
First decision: October 3, 2021
Revised: October 23, 2021
Accepted: January 11, 2022
Article in press: January 11, 2022
Published online: February 7, 2022
Abstract
BACKGROUND

Connective tissue growth factor (CTGF) is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling, inflammatory processes and fibrosis in various illnesses including cancer.

AIM

To investigate the role of CTGF in colorectal cancer (CRC) progression and to compare the CTGF expression with different clinicopathological parameters.

METHODS

Real-time polymerase chain reaction, immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16.

RESULTS

CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, and both lymphovascular and perineural invasion. As per the cox regression model and classification tree analysis, tumor-node-metastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients. Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival.

CONCLUSION

Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

Keywords: Connective tissue growth factor, Quantitative real time polymerase chain reaction, Immunohistochemistry, Western blotting, Colorectal cancer

Core Tip: This study demonstrates that connective tissue growth factor is overexpressed in colorectal carcinoma and is predominantly localized in the cytoplasm of the cell. The expression pattern of this gene showed a substantial association with aggressive phenotypes of colorectal cancer like late-stage tumor and lymph node metastasis. It also showed a significant correlation with the overall and disease-free survival of colorectal cancer patients, hence could act as a predictive biomarker for diagnostics and prognostics of colorectal cancer.