Abstract 3820: Expression of ST6Gal-1 in colorectal cancer and patient prognosis

Abstract

Abstract Background: ST6Gal-1 sialyltransferase, a type II membrane protein that catalyzes the transfer of sialic acid to the N-glycans of certain receptors, is upregulated in several cancers, including colorectal cancers (CRCs), and its levels correlate with metastatic potential. Therefore, we investigated its prognostic value in CRCs. Methodology: Formalin-fixed, paraffin-embedded CRC tissues from African Americans (Blacks) (n=50) and non-Hispanic Caucasians (Whites) (n=51) patients were evaluated for immunohistochemical (IHC) expression of ST6Gal-1. IHC expression was assessed using an anti-human ST6Gal-1 polyclonal antibody (R&D Systems) with antigen retrieval. The antibody-antigen complex was detected by the Immpact NovaRed system (Vector Labs). A semiquantitative immunostaining scoring system (ISS) on a scale of 0-4 was developed to assess the ST6Gal-1 expression, and a cutoff value (1.2 ISS) was determined by the bootstrap method. This value was used to classify tumors as low- or high-ST6Gal-I expressors. Previously, these tissues were evaluated for p53 nuclear accumulation (p53nac), an indicator of abnormal p53, by IHC. ST6Gal-1 expression levels were correlated with demographic and clinicopathologic features and with patient survival. Results: Increased ST6Gal-1 expression was observed in all CRCs as compared to their corresponding normal tissues. The overall frequency of CRCs with increased ST6Gal-1 expression was 80%; it was more commonly found in Blacks (88%, 44 of 50) than in Whites (70%, 36 of 51) (X2 p=0.031). Also, increased expression was associated with p53nac, and ST6Gal-1 expression was higher in CRCs that exhibited p53nac (87%, 42 of 48) relative to CRCs without p53nac (70%, 35 of 50) (X2 p = 0.034). Moreover, patients with CRCs with high ST6Gal-1 had lower median survival (29.3 months) relative to those with low ST6Gal-1 expression (58.5 months). Conclusions: These preliminary findings suggest that increased expression of ST6Gal-1 expression, found predominantly in Blacks patients and in CRCs with abnormal p53, is associated with poor patient survival. Citation Format: Trafina Jadhav, Saksham Narang, Jeehyun Bae, Matthew Schultz, Isam-Eldin Eltoum, Susan Bellis, Sejong Bae, Upender Manne. Expression of ST6Gal-1 in colorectal cancer and patient prognosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3820. doi:10.1158/1538-7445.AM2014-3820