Abstract 3489: Luminex-based analysis of serum CXC chemokines showing their usefulness as prognostic and/or predictive biomarkers in metastatic colorectal cancer patients
Authors: Cabrero-de las Heras Sara , Losa Ferran , Hernández-Yagüe Xavier , Soler Gemma , Bugés Cristina , Baraibar Iosune , Plaja Andrea , Teixidor Eduard , Martínez-Balibrea Eva 
Published: June 2022

Introduction: CXC chemokines are a family of small, secreted, chemotactic molecules acting through the binding to their corresponding CXC receptors (CXCRs) and stimulating the migration of cells, most notably those of the immune system. They have been associated with both pro-tumor and anti-tumor activity. Previously, we reported increased expression and secretion levels of CXCL1, 2 and 8 in oxaliplatin (OXA)-resistant colorectal cancer (CRC) cell lines. The aim of this study is to evaluate the usefulness of measuring the serum levels of a CXC chemokine panel in CRC patients as prognostic and/or predictive biomarkers of first-line treatment.

Material and Methods: In this multicenter study sera from advanced CRC patients to be treated with OXA-based schedules were collected at three different time points between November 2016 and June 2021: before treatment (PRET), at first response evaluation (EVAR) and at the time of progression/end of study (PROG). Levels of CXCL1, 2, 5, 6, 8, 9, 10, 11, 12, 13, 16 chemokines were analyzed using a custom Bio-plex Pro Human assay (Bio-Rad, USA) in a Luminex® 200 equipment. Comparisons of chemokines’ levels between Responders (R) and Non-Responders (NR) at different time-points were carried out using the Mann Whitney U and Wilcoxon tests. Log Rank and Cox regression were used to study differences in progression-free (PFS) and overall survival (OS); Chi-square or Fisher’s tests were used to study associations between categorical variables. All differences were considered statistically significant when p values ≤ 0.05.

Results: A total of 107 patients were enrolled in this study: 72% male; median age 66 years old; metastasis: 78% liver, 41% lung; mutations: 44% KRAS, 4% BRAF; treatments: FOLFOX/XELOX = 30%/4% plus Bevacizumab/anti-EGFR = 36%/24%; 64% responders (complete response + partial response); 13% stable disease; 11% progressors. All chemokines could be detected in the samples. Levels below median (LBM) of CXCL1, 8, 11 and 13 correlated with better OS (HR=0.55 p=0.02; HR=0.47 p=0.005; HR=0.6 p=0.05; HR=0.54 p=0.02, respectively). LBM of CXCL16 correlated with better OS and PFS (HR=0.6 p=0.04; HR=0.6 p=0.005) and of CXCL5 with better PFS (HR 0.6 p 0.011); mean CXCL9 levels were lower in responders’ PRET samples (p=0.03) and LBM correlated with better OS (HR=0.5 p=0.019). In responders, all chemokines except CXCL10, 13 and 16 presented decreased levels at EVAR vs. PRET. Moreover, CXCL1, 2, 5, 8, 11 and 16 levels increased at PROG vs. EVAR. In non-responders, non-conclusive results were found.

Conclusion: our results show that serum levels of specific CXC chemokines may be used as prognostic/predictive markers in metastatic CRC. Further analysis will be performed, and an update of this study will be presented in the AACR meeting.

Citation Format: Sara Cabrero-de las Heras, Ferran Losa, Xavier Hernández-Yagüe, Gemma Soler, Cristina Bugés, Iosune Baraibar, Andrea Plaja, Eduard Teixidor, Eva Martínez-Balibrea. Luminex-based analysis of serum CXC chemokines showing their usefulness as prognostic and/or predictive biomarkers in metastatic colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3489.