High expression of sialylated cancer-derived IgG and survival in metastatic clear cell renal cell carcinoma.

Abstract

443 Background: The treatment landscape of metastatic clear cell renal cell carcinoma (mccRCC) has evolved from cytokine regimens to targeted therapy, and now immunotherapy-based drug combinations over the past two decades. However, there is a lack of confirmed prognosis biomarkers for mccRCC patients. The International mRCC Database Consortium (IMDC) risk model is the most widely used effective biomarker for prognostication in mccRCC. Immunoglobulin G (IgG), well known as immune molecule secreted by B cells, has recently been detected in various types of cancer cells, named as cancer-derived IgG. Notably, it has been demonstrated that IgG derived from epithelial cancer cells displays unique N-glycosylation, which is highly sialylated (SIgG). In this study, we aimed to explore the expression of SIgG in mccRCC tissues using the monoclonal antibody RP215, and evaluated the correlation of SIgG expression level with clinicopathological factors and prognosis of mccRCC patients. Methods: A total of 179 mccRCC patients with complete clinicopathological information and survival data were enrolled. Tumor tissues were collected during surgery and fixed in 10% buffered formalin, embedded in paraffin. Tissue microarray slides were then constructed for immunohistochemistry (IHC). The primary end point was overall survival (OS), defined as the time from initiation of systemic treatment to death from any cause or last follow-up. Results: The results of IHC showed that SIgG was mainly expressed in the cell membrane and cytoplasm, and the high expression of SIgG was significant correlated with poor OS in mccRCC patients (HR = 2.281, P < 0.001). Moreover, based on multivariate Cox regression analysis, high SIgG expression was identified as an independent prognostic variable for OS in mccRCC patients (HR = 2.110, P < 0.001), as well as poor IMDC risk group (HR = 2.123, P = 0.018). The time-dependent ROC curve also suggested the promising prognostic value of SIgG expression, with a 5-year AUC of 0.679 for SIgG alone and 0.742 for SIgG combined with IMDC risk model. In addition, subgroup analyses were performed to further assess prognostic value of SIgG for mccRCC patients among groups based on IMDC risk group, metastatic site, and metastatic time. The prognostic value of SIgG was more marked in patients with intermediate (HR = 2.191, P = 0.019) and poor (HR = 2.111, P = 0.058) IMDC risk group, and lung metastasis (HR =1.970, P = 0.009). Notably, the prognostic value of SIgG was significant in both synchronous and metachronous metastasis patients. Conclusions: SIgG appears to be a reliable predictor for the outcome of mccRCC patients, and SIgG combined with IMDC risk model was a more effective prognostic model than IMDC risk group alone.