Circulating Soluble EGFR Correlates with Tumor Burden and Hepatic Reserve but Lacks Independent Prognostic Value in Hepatocellular Carcinoma: A Prospective Turkish Cohort.
- 1Department of Medical Oncology, Koc University Hospital, Istanbul, Turkey.
- 2School of Medicine, Koc University, Istanbul, Turkey.
- 3Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
Abstract
Purpose
Serum soluble epidermal growth factor receptor (sEGFR) is a circulating extracellular-domain EGFR fragment that is biologically distinct from membrane-bound tissue EGFR, and its clinical meaning in hepatocellular carcinoma (HCC) has not been defined. We evaluated whether baseline serum sEGFR is related to tumor burden and hepatic reserve, and whether it carries prognostic information independent of established clinical variables.Patients and methods
This prospective single-center cohort included 84 patients with HCC evaluated between November 2014 and May 2017. Baseline serum sEGFR was measured by ELISA. Overall survival (OS) was defined from baseline serum sample collection to death from any cause or last follow-up and was analyzed using Kaplan-Meier estimates, lg-rank testing, and Cox proportional hazards models with bootstrap internal validation. The incremental value of sEGFR over alpha-fetoprotein (AFP) and MELD-Na was tested in a combined model.Results
Lower serum sEGFR was associated with larger tumor size, higher AFP, higher aspartate aminotransferase and bilirubin levels, worse MELD-Na and Child-Turcotte-Pugh scores, lower insulin-like growth factor-1, and distant metastasis. Patients with sEGFR ≤13 ng/mL had shorter median OS than those with sEGFR >13 ng/mL (5.4 vs 12.1 months; log-rank p=0.0027; univariable HR 2.06, 95% CI 1.27-3.34). After adjustment for tumor size, log-transformed AFP, MELD-Na, portal vein thrombosis, and age, sEGFR was not associated with OS (HR 0.99, 95% CI 0.95-1.03, p=0.69), and the estimate remained close to the null across 1000 bootstrap resamples. Adding continuous sEGFR to a model containing AFP and MELD-Na did not improve discrimination (C-index 0.657 vs 0.656).Conclusion
Low serum sEGFR identifies an adverse tumor-liver phenotype and shorter unadjusted survival, but it is not an independent prognostic factor and adds no discriminative information beyond AFP and MELD-Na. Serum sEGFR is best regarded as a marker of disease phenotype; it does not perform as a stand-alone prognostic test.
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BibTeX
@article{lacin2026circulating,
title = {{Circulating Soluble EGFR Correlates with Tumor Burden and Hepatic Reserve but Lacks Independent Prognostic Value in Hepatocellular Carcinoma: A Prospective Turkish Cohort.}},
author = {Sahin Lacin and Rohat Esmer and Suayib Yalcin},
journal = {Journal of hepatocellular carcinoma},
year = {2026},
month = oct,
doi = {10.2147/jhc.s637289},
url = {https://europepmc.org/article/MED/42936266},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Circulating Soluble EGFR Correlates with Tumor Burden and Hepatic Reserve but Lacks Independent Prognostic Value in Hepatocellular Carcinoma: A Prospective Turkish Cohort.
AU - Sahin Lacin
AU - Rohat Esmer
AU - Suayib Yalcin
PY - 2026
DA - 2026/10/22
JO - Journal of hepatocellular carcinoma
DO - 10.2147/jhc.s637289
UR - https://europepmc.org/article/MED/42936266
AB - Purpose Serum soluble epidermal growth factor receptor (sEGFR) is a circulating extracellular-domain EGFR fragment that is biologically distinct from membrane-bound tissue EGFR, and its clinical meaning in hepatocellular carcinoma (HCC) has not been defined. We evaluated whether baseline serum sEGFR is related to tumor burden and hepatic reserve, and whether it carries prognostic information independent of established clinical variables.Patients and methods This prospective single-center cohort included 84 patients with HCC evaluated between November 2014 and May 2017. Baseline serum sEGFR was measured by ELISA. Overall survival (OS) was defined from baseline serum sample collection to death from any cause or last follow-up and was analyzed using Kaplan-Meier estimates, lg-rank testing, and Cox proportional hazards models with bootstrap internal validation. The incremental value of sEGFR over alpha-fetoprotein (AFP) and MELD-Na was tested in a combined model.Results Lower serum sEGFR was associated with larger tumor size, higher AFP, higher aspartate aminotransferase and bilirubin levels, worse MELD-Na and Child-Turcotte-Pugh scores, lower insulin-like growth factor-1, and distant metastasis. Patients with sEGFR ≤13 ng/mL had shorter median OS than those with sEGFR >13 ng/mL (5.4 vs 12.1 months; log-rank p=0.0027; univariable HR 2.06, 95% CI 1.27-3.34). After adjustment for tumor size, log-transformed AFP, MELD-Na, portal vein thrombosis, and age, sEGFR was not associated with OS (HR 0.99, 95% CI 0.95-1.03, p=0.69), and the estimate remained close to the null across 1000 bootstrap resamples. Adding continuous sEGFR to a model containing AFP and MELD-Na did not improve discrimination (C-index 0.657 vs 0.656).Conclusion Low serum sEGFR identifies an adverse tumor-liver phenotype and shorter unadjusted survival, but it is not an independent prognostic factor and adds no discriminative information beyond AFP and MELD-Na. Serum sEGFR is best regarded as a marker of disease phenotype; it does not perform as a stand-alone prognostic test.
SN - 2253-5969
ER -