Soluble HLA-G is a differential prognostic marker in sequential colorectal cancer disease stages

Abstract

The expression of HLA­G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA­G (sHLA­G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10­15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA­G levels in CRC patients, preoperative plasma sHLA­G levels were determined by ELISA in CRC patients (n=133). In addition, the local expression of HLA­G in tumour biopsies was assessed using tissue microarray analysis (n=255).

Within the high 33^rd percentile of sHLA­G levels (265–890 U/ml; n=44) we observed higher frequency of MC patients (P=0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (P=0.035; 2-tailed t-test). Moreover, MC patients had significantly higher sHLA­G levels compared to those with adenocarcinoma not otherwise specified (P=0.036; 2-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA­G levels and liver metastasis free survival (LMFS) (P=0.041; R=­0.321), in stage III patients high sHLA­G levels were associated with significantly longer LMFS (P=0.002), and sHLA­G levels displayed positive correlation with LMFS (P=0.006; R=0.409). High HLA­G expression in tumours was associated with poor cancer specific overall survival in stage II­III (P=0.01), and with shorter LMFS in stage II patients (P=0.004).

Our findings reveal that sHLA­G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC. This article is protected by copyright. All rights reserved.

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