Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients

Sep 21, 2026

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Background: Endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis are interconnected signaling pathways governing cell survival and death. This study assessed the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3 in colorectal cancer (CRC) and their association with clinicopathological features. Methods: A retrospective analysis used FFPE blocks from 2017–2019, applying tissue microarrays and SPSS statistics with P≤0.05. Results and conclusion summarize significant links between XBP1s or caspase-3 and tumor characteristics, while p62 showed no correlation; XBP1s may support personalized therapy.

LanguageEnglish

CategoryResearch & Report

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Pages12

Reading Time30 min

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What’s Known

What’s New

Abstract

Background

Methods

Results

Conclusion

Introduction

IJMS Vol 49, No 1, January 2024 Original Article Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients Mohammadkian Zarafshani1,2 , MD; Habibollah Mahmoodzadeh2 , MD; Vahid Soleimani3 , MD; Mohammad Amin Moosavi4 , PhD; Marveh Rahmati1, PhD 1Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran; 2Division of Surgical Oncology, Department of Surgery, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran; 3 Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, Institute of Medical Biotechnology (IMB), National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran Correspondence: Marveh Rahmati, PhD; Cancer Biology Research Center, Cancer Institute, Imam Khomeini Hospital, Dr. Gharib St. , Keshavarz Blvd. , Postal code: 14197-33141, Tehran, Iran Tel: +98 21 66940021 [Email:](Email: m_rahmati@sina.tums.ac.ir)[ m_rahmati@sina.tums.ac.ir](Email: m_rahmati@sina.tums.ac.ir) [Received: 09 October 2022](Received: 09 October 2022) [Revised: 14 January 2023](Revised: 14 January 2023) [Accepted: 03 February 2023](Accepted: 03 February 2023) |
What’s Known
• The vital mechanism mediating cell survival and death include endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis.
• In cancer patients, XBP1s, p62, and caspase-3 are known as critical biomarkers of ERS, autophagy, and apoptosis.

What’s New | | --- | | • There was a significant correlation between the clinical stages and the expression of XBP1s in tumor tissues.
• XBP1s have the potential to be considered as a targeted treatment for CRC tumors. | Abstract Background: Three main cell signaling pathways including the endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis play critical roles in both cell survival and death. They were found to crosstalk with one another during tumorigenesis and cancer progression. This study aimed to investigate the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3, as the essential biomarkers of ERS, autophagy, and apoptosis in patients with colorectal cancer (CRC), as well as the correlation between their expression and clinicopathological data. Methods: This retrospective study was conducted on formalinfixed paraffin-embedded (FFPE) blocks, which were collected from patients and their tumor margins, from the tumor bank of Imam Khomeini Hospital (Tehran, Iran) from 2017 to 2019. Tissue microarray (TMA) was used to measure the XBP1s, p62, and caspase-3 biomarkers. Data were analyzed using SPSS software version 20, and P≤0.05 was considered statistically significant. Results:Evaluating the total of 91 patients, a significant relationship was found between XBP1s expression and TNM stage (P=0.003), primary tumor (pT) (P=0.054), and the degree of differentiation (P=0.006); and between caspase-3 with pT (P=0.004), and lymphovascular invasion (P=0.02). However, no significant correlation was found between p62 and clinicopathological data. Furthermore, a positive relationship between XBP1s and p62 was confirmed (correlation coefficient: 22.2% and P=0.05). Conclusion: Our findings indicated that XBP1s could be considered as a target for therapy in personalized medicine. Please cite this article as: Zarafshani MK, Mahmoodzadeh H, Soleimani V, Moosavi MA, Rahmati M. Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients. Iran J Med Sci. 2024;49(1):10-21 . doi: 10.30476/IJMS.2023.96922.2856. Keywords ● Apoptosis ● Autophagy ● Caspase-3 ● Colorectal neoplasm ● Endoplasmic reticulum stress Introduction Colorectal cancer (CRC) is one of the most prevalent cancers of the gastrointestinal tract and is known as the third caus

FAQs

What signaling pathways are examined in this study of colorectal cancer?

The study focuses on the ERS response, autophagy, and apoptosis, emphasizing their crosstalk during tumorigenesis and cancer progression.

How were XBP1s, p62, and caspase-3 levels measured?

Levels were measured using tissue microarray (TMA) on formalin-fixed paraffin-embedded (FFPE) blocks from CRC patients and tumor margins.

Which biomarkers showed significant correlations with clinicopathological data?

XBP1s correlated significantly with TNM stage and with differentiation; caspase-3 correlated with primary tumor stage and lymphovascular invasion, while p62 showed no significant correlation.

Sep 21, 2026

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