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

Iran J Med Sci. 2024 Jan 1;49(1):10-21. doi: 10.30476/IJMS.2023.96922.2856. eCollection 2024 Jan.


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 formalin-fixed 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.

Keywords: Apoptosis; Autophagy; Caspase-3; Colorectal neoplasm; Endoplasmic reticulum stress.

MeSH terms

  • Biomarkers
  • Caspase 3* / genetics
  • Clinical Relevance
  • Colorectal Neoplasms* / genetics
  • Humans
  • Iran
  • Protein Serine-Threonine Kinases / metabolism
  • Retrospective Studies
  • X-Box Binding Protein 1* / genetics


  • Biomarkers
  • Caspase 3
  • Protein Serine-Threonine Kinases
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • nuclear pore protein p62
  • CASP3 protein, human