Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Frontiers in Genetics

Genetics

Dusica Gavrilovic¹  Rafael Stroggilos²  Jerome Zoidakis³  Aleksandra Stanojevic⁴  Milena Cavic⁴  Marija Ostojic⁴  Radmila Jankovic⁴  Remond J. A. Fijneman⁵  Mladen Marinkovic⁶  Suzana Stojanovic-Rundic⁷  Sergi Castellví-Bel⁸  Natasa Maksimovic⁹ 

[1] Data Center, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia;Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece;Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece;Department of Biology, National and Kapodistrian University of Athens, Athens, Greece;Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia;Department of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands;Department of Radiation Oncology, Clinic for Radiation Oncology and Diagnostics, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia;Department of Radiation Oncology, Clinic for Radiation Oncology and Diagnostics, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia;Faculty of Medicine, University of Belgrade, Belgrade, Serbia;Gastroenterology Department, Fundació Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Clínic Barcelona, University of Barcelona, Barcelona, Spain;Institute of Epidemiology, University of Belgrade, Belgrade, Serbia;

关键词: inflammation;    locally advanced rectal cancer;    neoadjuvant chemoradiotherapy;    predictive biomarkers;    hematological parameters;   

DOI  :  10.3389/fgene.2023.1245594

 received in 2023-06-23, accepted in 2023-08-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response.Materials and methods: In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020—January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested (“watch and wait” approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5.Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05).Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.

【 授权许可】

Unknown   
Copyright © 2023 Marinkovic, Stojanovic-Rundic, Stanojevic, Ostojic, Gavrilovic, Jankovic, Maksimovic, Stroggilos, Zoidakis, Castellví-Bel, Fijneman and Cavic.