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Serum Autoantibodies against STIP1 as a Potential Biomarker in the Diagnosis of Esophageal Squamous C 时间:2017-08-30 14:55 来源:未知作者:admin 点击: 次 Abstract:Esophageal squamous cell carcinoma (ESCC) remains one of the leading causes of cancer-related mortality around the world. The identification of novel serum biomarkers is required for early detection of ESCC. This study was designed to elucidate whether autoantibodies against STIP1 could be a diagnostic biomarker in ESCC. An enzyme-linked immunosorbent assay was performed to detect serum levels of STIP1 autoantibodies in a training cohort (148 ESCC patients and 111 controls) and a validation cohort (60 ESCC patients and 40 controls). Mann–Whitney’s U test showed that ESCC patients in two cohorts have higher levels of autoantibodies against STIP1 when compared to controls (). According to receiver operating characteristic analysis, the sensitivity, specificity, and area under the curve (AUC) of autoantibodies against STIP1 in ESCC were 41.9%, 90.1%, and 0.682 in the training cohort and 40.0%, 92.5%, and 0.710 in the validation cohort, respectively. Moreover, detection of autoantibodies against STIP1 could discriminate early-stage ESCC patients from controls, with sensitivity, specificity, and AUC of 35.7%, 90.1%, and 0.684 in the training cohort and 38.5%, 92.5%, and 0.756 in the validation cohort, respectively. Our findings indicated that autoantibodies against STIP1 might be a useful biomarker for early-stage ESCC detection.
1. Introduction
Esophageal cancer (EC) is the eighth most prevalent malignant disease and the sixth leading cancer-related deaths around the world [1]. In China, 477,900 EC patients were diagnosed and 375,000 patients died in 2015. Among them, the number of male patients was as twice as that of female patients [2]. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma are two predominant subtypes of EC. In China, 90% of cases are ESCC, compared to only 26% in the United States [3]. Despite many advances in the treatments of patients with EC, the 5-year survival rate remains poor (e.g., 17.4% in the United States) [4]. The survival rate of EC could reach up to 85% when diagnosed at an early stage but is no more than 10% if diagnosed at an advanced stage [5]. Thus, early diagnosis offers a great opportunity to receive effective therapy and reduce ESCC mortality, and the discovery of noninvasive screening methods is urgently needed.
Serological tests are found to be one of the promising methods for improvement of the early detection of cancer. However, ESCC lacks effective and reliable serological biomarker for early detection and disease surveillance. Actually, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), and CYFRA21-1 were the most widely used serum biomarkers for ESCC, but the performance of these biomarkers to detect early-stage ESCC is deficient [6–8]. Novel biomarkers with high diagnostic accuracy are greatly needed to improve detection of ESCC. In the last decade, numerous studies have indicated that autoantibodies against tumor-associated antigens (TAAs), as reporters from the immune system, exist in cancer patients, and autoantibodies against TAAs are thought to be ideal targets as noninvasive serological tests for early detection of cancer [9–11]. Therefore, autoantibodies could be a valuable source of serum biomarkers used for identifying early ESCC.
Stress-induced phosphoprotein 1 (STIP1), also known as HOP, P60, STI1, and so forth, is a 66.2-kilodalton chaperone protein which plays important roles in stress and nonstress conditions. Its 2.0-kilobase-encoded mRNA was first isolated from the yeast Saccharomyces cerevisiae [12]. STIP1 is one of the cochaperones that are most extensively studied and contains three tetratricopeptide repeat (TPR) domains, which can simultaneously bind Hsp70 and Hsp90 [13, 14]. STIP1 was identified to be overexpressed in several kinds of cancers, such as colorectal carcinoma (CRC) [15], pancreatic cancer [16], cholangiocellular carcinoma (CCC) [17], ovarian cancer [18], and so on. Moreover, increased expression of STIP1 may indicate poor survival outcome in cancer patients [18, 19]. STIP1 was also identified as a TAA recognized by the humoral immune system by means of serological analysis of recombinant cDNA expression library approach [20]. A recent study showed that autoantibodies against STIP1 were significantly elevated in the serum levels of patients with ovarian cancer, compared with the normal controls [21]. However, no study has been conducted on STIP1 autoantibodies in esophageal cancer. The present study was then undertaken to investigate whether autoantibodies against STIP1 could be altered and used as a candidate diagnostic biomarker in ESCC.