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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Lymphocyte to C-reactive protein ratio as a novel inflammatory biomarker: Validation and clinical relevance as an independent prognostic factor in cholangiocarcinoma
Fan Xiao, De-Hua Zhou, Guo-Wei Liu, Chao-Wei Lin, Zi-You Wu, Hua Yu, Wei Gong, Wei-Feng Tan
Fan Xiao, Wei-Feng Tan, Hepatobiliary Surgery Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, China
De-Hua Zhou, Department of Gastrointestinal Surgery, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, China
Guo-Wei Liu, Department of General Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
Chao-Wei Lin, Technical Support, Jingyin Electronic Technology, Shanghai 200030, China
Zi-You Wu, Wei Gong, Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zi-You Wu, Department of Hepatobiliary Surgery, Southwest Hospital Affiliated to the Third Military Medical University (Army Medical University), Chongqing 400000, China
Hua Yu, Department of General Surgery, Shanghai Fourth People’s Hospital School of Medicine Tongji University, Shanghai 200434, China
Co-first authors: Fan Xiao and De-Hua Zhou.
Author contributions: Xiao F and Zhou DH contributed equally to this work as co-first authors. Xiao F led the study design, data interpretation, and manuscript drafting; Zhou DH performed critical experiments, data analysis, and contributed to figure preparation; Liu GW and Lin CW conducted statistical analyses and verified data accuracy; Wu ZY assisted in experimental processes and data management; Yu H and Gong W contributed to methodological development and manuscript revision; Tan WF oversaw the entire project, secured funding, and provided critical revisions for intellectual content.
Supported by National Natural Science Foundation of China, No. 82170412.
Institutional review board statement: This retrospective study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Ethics Committee of Shanghai Fourth People’s Hospital (Approval No. 2025097-001).
Informed consent statement: This study is a retrospective analysis utilizing de-identified historical data. All information was anonymized prior to use, ensuring patient confidentiality. In accordance with ethical guidelines, the hospital’s ethics committee approved the study and waived the requirement for individual informed consent, given the non-interventional nature of the research and the use of pre-existing, de-identified data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets are available from the corresponding author upon reasonable request.
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 ori
ginal work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Wei-Feng Tan, MD, PhD, Professor, Hepatobiliary Surgery Center, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincheng Road, Putuo District, Shanghai 200092, China.
twf1231@163.com
Received: September 5, 2025
Revised: September 28, 2025
Accepted: November 3, 2025
Published online: December 15, 2025
Processing time: 97 Days and 19.8 Hours
BACKGROUND
Inflammatory cytokines are associated with cancer prognosis, but their specific role in cholangiocarcinoma remains poorly understood. The lymphocyte to C-reactive protein ratio (LCR), a novel inflammatory-nutritional biomarker, has demonstrated predictive value in gastrointestinal cancers; however, its clinical relevance in cholangiocarcinoma has not been investigated.
AIM
To validate the LCR as an independent prognostic factor for overall survival (OS), surgical site infection (SSI), and length of hospital stay in patients with resectable cholangiocarcinoma.
METHODS
We conducted a retrospective analysis of 76 patients with cholangiocarcinoma who underwent radical surgery between 2008 and 2013. The preoperative LCR was calculated as the lymphocyte count divided by C-reactive protein level, using a cutoff value of 180. Univariate and multivariate logistic regression analyses were performed to evaluate factors associated with SSI and hospitalization duration, while Kaplan-Meier survival curves and Cox proportional hazards models were used to assess predictors of OS.
RESULTS
Patients in the low LCR group was significantly associated with several adverse clinical outcomes: A shorter median OS (14.93 months vs 46.67 months; P = 0.022); a 4.5-fold increased risk of prolonged hospitalization (P = 0.007); and a higher incidence of SSI (odds ratio = 4.41, P = 0.045). Multivariate analysis confirmed that LCR was an independent predictor of OS [hazard ratio (HR) = 3.204, P = 0.002], SSI, and hospitalization duration. Additionally, R0 resection (HR = 3.546, P = 0.002) and advanced tumor-node-metastasis stage (HR = 2.016, P = 0.035) were identified as independent prognostic factors for OS.
CONCLUSION
In this retrospective study, preoperative LCR is a cost-effective and practical biomarker that independently predicts OS, postoperative complications, and hospitalization duration in patients with resectable cholangiocarcinoma, thereby facilitating more precise patient stratification.
Core Tip: This pioneering study establishes the lymphocyte to C-reactive protein ratio (LCR) as the first validated inflammatory biomarker for predicting survival and postoperative outcomes in cholangiocarcinoma. We demonstrate that a low preoperative LCR (< 180) independently correlates with a 4.5-fold increase in the risk of prolonged hospitalization, elevated risk of surgical site infections (odds ratio = 4.41), and significantly reduced median survival (14.93 months vs 46.67 months). As a cost-effective prognostic tool, LCR facilitates refined patient stratification, thereby supporting optimized surgical decision-making and postoperative management.
