Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 6, 2022; 10(13): 4084-4096
Published online May 6, 2022. doi: 10.12998/wjcc.v10.i13.4084
High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer
Zoltan Herold, Magdolna Herold, Gyorgy Herczeg, Agnes Fodor, Attila Marcell Szasz, Magdolna Dank, Aniko Somogyi
Zoltan Herold, Attila Marcell Szasz, Magdolna Dank, Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
Zoltan Herold, Magdolna Herold, Aniko Somogyi, Department of Internal Medicine and Hematology, Semmelweis University, Budapest H-1088, Hungary
Gyorgy Herczeg, Agnes Fodor, Department of General Surgery, Szent Imre University Teaching Hospital, Budapest H-1115, Hungary
Author contributions: Herold Z, Herold M, and Somogyi A built the study design; Herold M, Herczeg G, Fodor A, and Herold Z were involved in the collection of samples; Herold Z analyzed the data; Herold Z, Herold M, Herczeg G, Szasz AM, and Dank M interpreted data; Herold Z prepared the draft of the manuscript; all authors were involved in editing and reviewing; Somogyi A and Herold Z received funding; Somogyi A supervised the study; all authors have read and agreed to the published version of the manuscript.
Supported by the National Research, Development and Innovation Office, No. K-116128; and the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund, No. UNKP-20-4-I.
Institutional review board statement: The study was reviewed and approved by the Regional and Institutional Committee of Science and Research Ethics, Semmelweis University (SE TUKEB 21-12/1994, approval date of latest modification: February 10, 2017), the Institutional Review Board of Szent Imre University Teaching Hospital (SZIK IKEB 5/2017), and the Committee of Science and Research Ethics, Hungarian Medical Research Council (ETT TUKEB 8951-3/2015/EKU).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent before study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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 original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zoltan Herold, MSc, PhD, Research Scientist, Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 25-29 Tomo u, Budapest H-1083, Hungary. herold.zoltan@med.semmelweis-univ.hu
Received: April 24, 2021
Peer-review started: April 24, 2021
First decision: June 13, 2021
Revised: June 25, 2021
Accepted: April 2, 2022
Article in press: April 2, 2022
Published online: May 6, 2022
Processing time: 370 Days and 19.2 Hours
ARTICLE HIGHLIGHTS
Research background

The role of CD40 ligand (CD40L) is controversial in colorectal cancer (CRC). Higher circulating CD40L levels of CRC patients are known, but their relationship with disease staging and local and distant metastasis is not clear.

Research motivation

To our knowledge, no previous study investigated the relationship between CD40L and CRC-related thrombocytosis. Furthermore, no study was conducted to observe if CD40L changes with the course of CRC.

Research objectives

To analyze the clinical characteristics and laboratory results of 106 CRC patients and evaluate CD40L, interleukin-6, thrombopoietin level, and platelet count changes with the course of the disease; and to evaluate their effect on patient survival.

Research methods

CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay and interleukin-6 via electrochemiluminescence immunoassay. Measurements were conducted at the time of CRC diagnosis, at least 6 wk after primary tumor removal surgery, and at least 6 mo after primary tumor removal surgery.

Research results

CD40L of CRC patients was significantly higher in the presence of distant metastasis and/or thrombocytosis. CD40L was constant with the course of CRC, and all baseline differences persisted throughout the whole study. Both pre- and postoperative elevated CD40L were associated with poor overall and disease-specific survival of patients. The negative effect of CD40L on patient survival remained even after the stratification by thrombocytosis.

Research conclusions

CD40L level of CRC patients does not change with the course of the disease. The CD40L level is strongly correlated with platelet count, interleukin-6, thrombocytosis, and the presence of distant metastases. The effect of CD40L on patient survival cannot be fully eliminated via stratification by thrombocytosis. This suggests that the circulating amount of platelets is not the only factor behind its elevation.

Research perspectives

High plasma CD40L levels of CRC patients are with high probability not only dependent on circulating platelet count. General inflammation caused by the tumor could also contribute to CD40L elevation; therefore, further studies are required to clarify this question.