Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer

Giulia Turri; Simone Caligola; Stefano Ugel; Cristian Conti; Silvia Zenuni; Valeria Barresi; Andrea Ruzzenente; Giuseppe Lippi; Aldo Scarpa; Vincenzo Bronte; Alfredo Guglielmi; Corrado Pedrazzani

doi:10.3389/fonc.2023.1148197

Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer

Front Oncol. 2023 Jun 5:13:1148197. doi: 10.3389/fonc.2023.1148197. eCollection 2023.

Affiliations

¹ Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.
² Istituto Oncologico Veneto IRCCS, Padova, Italy.
³ Immunology Section, University Hospital and Department of Medicine, University of Verona, Verona, Italy.
⁴ Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.
⁵ Department of Neurological, Biomedical and Movement Sciences, Section of Clinical Biochemistry, University of Verona, Verona, Italy.

Abstract

Introduction: Emerging evidence is pointing towards a relevant role of immunity in cancer development. Alterations in leukocytes count and neutrophil-to-lymphocyte ratio (NLR) at diagnosis of colorectal cancer (CRC) seems to predict poor prognosis, but no data is available for the pre-diagnostic values.

Methods: Retrospective analysis of patients who underwent surgery for CRC at our center (2005 - 2020). 334 patients with a complete blood count dating at least 24 months prior to diagnosis were included. Changes in pre-diagnosis values of leukocytes (Pre-Leu), lymphocytes (Pre-Lymph), neutrophils (Pre-Neut), and NLR (Pre-NLR) and their correlation with overall- (OS) and cancer-related survival (CRS) were analyzed.

Results: Pre-Leu, Pre-Neut and Pre-NLR showed an increasing trend approaching the date of diagnosis, while Pre-Lymph tended to decrease. The parameters were tested for associations with survival after surgery through multivariable analysis. After adjusting for potential confounding factors, Pre-Leu, Pre-Neut, Pre-Lymph and Pre-NLR resulted independent prognostic factors for OS and CRS. On sub-group analysis considering the interval between blood sampling and surgery, higher Pre-Leu, Pre-Neut, and Pre-NLR and lower Pre-Lymph were associated with worse CRS, and the effect was more evident when blood samples were closer to surgery.

Conclusion: To our knowledge, this is the first study showing a significant correlation between pre-diagnosis immune profile and prognosis in CRC.

Keywords: colorectal cancer; diagnosis; inflammation; inflammatory markers; leucocytes; prognosis.

Grants and funding

This research was funded by Open Access Funding provided by UNIVERSITA’ DEGLI STUDI DI VERONA within the CRUI-CARE Agreement. WOA Institution: Università degli Studi di Verona. Blended DEAL: CARE. Also funded by S. Ugel grants of the Fondazione Italiana per la Ricerca sul Cancro (AIRC) ( MFAG project: 21509), PRIN program (MIUR, CUP: B38D19000140006) and Research and National Center for Gene Therapy and Drugs based on RNA Technology (application code CN00000041, Mission 4, Component 2 Investment 1.4, funded from the European Union - NextGenerationEU, CUP B33C22000630001) of Italian Ministry of Education, University.