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Peer-reviewedCC BY 4.0PLOS One

Claudin-18 expression is associated with poorer overall survival in colorectal cancer

  • Aya Y. Al-Kabariti1
  • Manal A. Abbas2
  • Maxim Alashhab3
  • Sneha Smarakan4
  • Maher A. Sughayer5
5 affiliations
  1. 1Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
  2. 2Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan
  3. 3Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan
  4. 4Institute of Cancer Therapeutics, Faculty of Health and Social Care, University of Bradford, West Yorkshire, United Kingdom
  5. 5Faculty of Medicine, The University of Jordan, Amman, Jordan
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Abstract

Claudin 18, a tight junction protein, has emerged as a therapeutic target in various gastrointestinal cancers, notably gastric adenocarcinoma. However, its prevalence and clinicopathological significance in colorectal cancer (CRC) remain incompletely understood. In the current single-center, retrospective, immunohistochemical study, the prevalence and prognostic value of Claudin-18 was investigated in CRC. Claudin-18 expression was detected in 15.9% (17/107) of CRC cases, with negative/weak expression in 84.1% (90/107). No significant associations were observed between Claudin-18 expression and age, sex, tumor site, T stage, lymph node status, distant metastasis, TNM stage, histological subtype, or lymphovascular invasion (all p > 0.05). No significant associations were identified between Claudin-18 expression and age, sex, tumor location, histological subtype, or TNM stage. Furthermore, Claudin-18 expression independently predicted survival outcomes in CRC where Kaplan–Meier analysis demonstrated significantly worse overall survival (OS) in patients with strong/moderate Claudin-18 expression compared with Claudin-18 -negative/weak expression (log rank test, p = 0.024). Mean OS was markedly longer in Claudin-18 -negative/weak expression group (121.0 vs.76.6 months). Progression-free survival (PFS) analysis demonstrated a trend toward poorer outcomes among patients with increased Claudin-18 expression; however, the difference did not reach statistical significance (log-rank test, p = 0.066). Event-free survival (EFS) was also significantly reduced in patients with strong/moderate Claudin-18 expression (log-rank test, p = 0.022). Mean EFS was markedly longer in CLDN18 negative/weak expression (93.1 vs. 31.1 months). Multivariable binary logistic regression showed that the overall model was statistically significant (χ2(7) = 22.657, p = 0.002). However, none of the evaluated variables—including gender, age, lymphovascular invasion, tumor laterality, TNM stage, MSI status, histological type, and Claudin-18 expression—was independently associated with the outcome (all p > .05). Claudin-18 expression was not a significant predictor in the adjusted model (p = 0.931; OR = 0.63). In conclusion, despite its low prevalence in the current cohort, Claudin-18 expression was associated with poorer overall survival; however, its independent prognostic value was not established.

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Cite

BibTeXRIS
BibTeX
@article{alkabariti2026claudin18,
  title = {{Claudin-18 expression is associated with poorer overall survival in colorectal cancer}},
  author = {Aya Y. Al-Kabariti and Manal A. Abbas and Maxim Alashhab and Sneha Smarakan and Maher A. Sughayer},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0360740},
  url = {https://doi.org/10.1371/journal.pone.0360740},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Claudin-18 expression is associated with poorer overall survival in colorectal cancer
AU  - Aya Y. Al-Kabariti
AU  - Manal A. Abbas
AU  - Maxim Alashhab
AU  - Sneha Smarakan
AU  - Maher A. Sughayer
PY  - 2026
DA  - 2026/10/26
JO  - PLOS One
DO  - 10.1371/journal.pone.0360740
UR  - https://doi.org/10.1371/journal.pone.0360740
AB  - Claudin 18, a tight junction protein, has emerged as a therapeutic target in various gastrointestinal cancers, notably gastric adenocarcinoma. However, its prevalence and clinicopathological significance in colorectal cancer (CRC) remain incompletely understood. In the current single-center, retrospective, immunohistochemical study, the prevalence and prognostic value of Claudin-18 was investigated in CRC. Claudin-18 expression was detected in 15.9% (17/107) of CRC cases, with negative/weak expression in 84.1% (90/107). No significant associations were observed between Claudin-18 expression and age, sex, tumor site, T stage, lymph node status, distant metastasis, TNM stage, histological subtype, or lymphovascular invasion (all p > 0.05). No significant associations were identified between Claudin-18 expression and age, sex, tumor location, histological subtype, or TNM stage. Furthermore, Claudin-18 expression independently predicted survival outcomes in CRC where Kaplan–Meier analysis demonstrated significantly worse overall survival (OS) in patients with strong/moderate Claudin-18 expression compared with Claudin-18 -negative/weak expression (log rank test, p = 0.024). Mean OS was markedly longer in Claudin-18 -negative/weak expression group (121.0 vs.76.6 months). Progression-free survival (PFS) analysis demonstrated a trend toward poorer outcomes among patients with increased Claudin-18 expression; however, the difference did not reach statistical significance (log-rank test, p = 0.066). Event-free survival (EFS) was also significantly reduced in patients with strong/moderate Claudin-18 expression (log-rank test, p = 0.022). Mean EFS was markedly longer in CLDN18 negative/weak expression (93.1 vs. 31.1 months). Multivariable binary logistic regression showed that the overall model was statistically significant (χ2(7) = 22.657, p = 0.002). However, none of the evaluated variables—including gender, age, lymphovascular invasion, tumor laterality, TNM stage, MSI status, histological type, and Claudin-18 expression—was independently associated with the outcome (all p > .05). Claudin-18 expression was not a significant predictor in the adjusted model (p = 0.931; OR = 0.63). In conclusion, despite its low prevalence in the current cohort, Claudin-18 expression was associated with poorer overall survival; however, its independent prognostic value was not established.
SN  - 1932-6203
ER  -