Abstract 3807: CXCL9:SPP1 macrophage polarity as a prognostic biomarker for localized colorectal cancer after surgical resection

Abstract Background: There is an unmet need for additive predictive biomarkers for the recurrence of stage II/III colorectal cancer (CRC) after surgery. As recent studies showing the potential prognostic role of macrophage polarity defined by CXCL9 and SPP1, instead of conventional M1 and M2, we tried to evaluate the prognostic role of this biomarker in real-world practice setting, delineating biologic mechanisms. Method: The RNA sequencing data of 273 tumors derived from patietns with stage II/III colorectal cancer who underwent surgical resection in 5 Korean cancer-centers were available for analysis. We initially divided two subgroups based on the ratio of expression level of CXCL9 per SPP1 expressions (CS ratio) and evaluated prognostic outcomes and compared immune cell proportions by deconvolutional method between subgroups. Result: The CS ratio was higher in consensus molecular subtype (CMS) 2 or CMS3 than others, and no significant differences were observed according to sidedness, stage, microsatellite instability status and medical centers. Total 69 (25, 3%) patients were classified as low level of CS ratio group, and there were no significant differences in baseline characteristics, including age, sex, CMS, sidedness, stage, microsatellite instability status and medical centers. With a median follow-up of 58. 2 months, the low CS ratio group showed poor 5-year recurrence-free survival (50. 6 vs. 71. 1%, HR=2. 27, P = 0. 002) and 5-year overall survival (69. 7% vs. 85. 9%, HR=1. 75, P = 0. 033). These trends were consistent across the subgroups. In the multivariate analyses including the potential prognostic factors (P 0. 1 in the univariate analyses), low CS ratio was significantly associated with poorer for RFS (adjusted HR = 1. 96, P = 0. 011) and OS (adjusted HR = 1. 81, P = 0. 002). These trends were consistent in the TCGA dataset (5 years OS: 69. 7% vs. 85. 9%, HR=1. 98, P = 0. 011). The low CS ratio group showed upregulated WNT signaling, and extracellular matrix organization pathway. Immune cell deconvolutional method exhibited the low CS ratio group showed more proportion of neutrophils, monocytes, whereas CD8+T cells, activated memory CD4+T cells were decreased, compared to high CS ratio group. Conclusions: These results suggest that CS ratio could be an applicable prognostic biomarker in locally advanced colorectal cancer after surgical resection. Based on this classification, more advanced treatment strategy may be required for low CS ratio group to improve surgical outcomes. Citation Format: Yeong Hak Bang, Ji Hye Choi, Hyunsu Kim, Kyunghee Park, Dae Hee Pyo, Yong Beom Cho, Woong-Yang Park. CXCL9: SPP1 macrophage polarity as a prognostic biomarker for localized colorectal cancer after surgical resection abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3807.