Basic Study
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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:
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.
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
Research background

Colorectal cancer (CRC) is one of the deadliest cancers, having a high death rate. Despite considerable advances in diagnostics and treatments, early detection remains difficult, resulting in a poor prognosis, which is exacerbated by deregulation of critical genes that contribute to disease development.

Research motivation

To investigate the role of connective tissue growth factor (CTGF) in CRC in order to improve the disease diagnosis and prognosis.

Research objectives

To evaluate the expression pattern and localization of CTGF in CRC and correlate it with various clinicopathological variables which might serve as effective preliminary predictive and therapeutic biomarker and aid in future CRC therapies in the Kashmir valley.

Research methods

A total of 71 histopathological confirmed CRC tissues and their adjacent normal specimens were included in this investigation. Real time polymerase chain reaction and western blot were employed to assess CTGF mRNA and protein levels, respectively. Immunohistochemistry was used for confirmation of the CTGF localization. CTGF expression was correlated with various clinicopathological characteristics, and survival analysis was performed on CRC patients to determine whether CTGF plays a predictive role in CRC.

Research results

CTGF expression in tumor samples were significantly higher than in adjacent normal samples. Higher levels of CTGF expression were associated with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, lymphovascular and perineural invasion. Tumor-node-metastasis stage and PNI were major predictors of CTGF expression and prognosis in CRC patients, according to the cox regression model and classification tree analysis. CTGF overexpression was linked to poor overall and disease-free survival (DFS), according to a survival analysis.

Research conclusions

CTGF was shown to be overexpressed and cytoplasmic in CRC tumor tissues, according to the findings. Overexpression was related to an aggressive phenotype in CRC patients, as well as poor overall and disease-free survival.

Research perspectives

The study strongly indicates that higher CTGF levels in CRC patients can be employed as predictive biomarker. Furthermore, CTGF overexpression may serve as a predictive biomarker for patients undergoing a distinct regimen of chemotherapeutic interventions. In order to validate these findings, future investigations with high sample size are needed to completely understand the mechanism of CTGF-induced CRC advancement.