The prognostic significance of B7-H3 expression in patients with advanced colorectal cancer

Biomarkers, particularly prognostic and immune based, are lacking in colorectal cancer (CRC). This study aimed to evaluate the expression of novel immune based biomarkers among patients with CRC to predict clinical outcomes.

A CRC tumor microarray (TMA) was developed from a multiracial patient population, and expression of diagnostic markers (CK7, CK20, CDX2) and immune based (HHLA2, B7-H3, PD-L1) determined by immunohistochemistry (IHC) in a novel quantitative manner. Comprehensive clinical information was extracted. Among patients with metastatic (m) cancers, Kaplan Meier curves were plotted, and Cox proportional hazards regression analysis was performed to evaluate association with overall survival (OS).

Among 388 patients, 150 had de novo metastatic disease, 108 experienced relapses from localized cancer, and 130 patients had cured localized disease. Racially/ethnically, 70 were non-Hispanic whites (NHW), 159 were non-Hispanic blacks (NHB), 147 Hispanic, and 12 Asian. The median age was 62 years, with a female predominance (53%). Among the patients with metastatic CRC, that included those with relapses and with de novo metastatic CRC (n = 258), in a multivariable Cox proportional hazards model, left sidedness (HR 0.52; 95%CI 0.35 - 0.77, p < 0.001) and low expression of both PD-L1 and B7-H3 was associated with better OS (HR 1.73; 95%CI 1.08-2.76, p = 0.023).

In this multiracial TMA of CRC, in a robust multivariable model, following REMARK guidelines, we validate our prior findings that low expression of both B7-H3 and PD-L1 is prognostic for OS among patients with mCRC. Given the rapid proliferation of B7-H3 targeted drug development in clinical trials, these findings may help create a platform for future research to delineate their predictive role in a bespoke therapeutic approach.