Serum Autoantibodies against STIP1 as a Potential Biomarker in the Diagnosis of Esophageal Squamous Cell Carcinoma

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 (P < 0.001). 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.

A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis

“…Stress-induced phosphoprotein 1 (STIP1), also known as HOP/P60/STI1, is a chaperone protein that comprises three tetratricopeptide repeat domains, which can simultaneously bind HSP70s and HSP90s. STIP1 is a tumour-associated antigen (TAA) 33 ; its overexpression has been identified in numerous cancers, including colorectal carcinoma 34 , pancreatic cancer 35 , cholangiocellular carcinoma 36 and ovarian cancer 37 , and it is possibly associated with poor survival outcomes in patients with cancer 38 . ST13 encodes ST13 HSP70s-interacting protein (HIP)/putative tumour suppressor ST13/suppression of tumorigenicity 13 protein, which is also involved in the regulation of heat shock factor 1 (HSF1)-mediated heat shock response and which mediates the association of HSP70s and HSP90s.…”

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

“…Mann‐Whitney U test exhibited higher levels of autoantibodies against ST1P1 in ESCC patients when compared to HC. The detection of autoantibodies against STIP1 could discriminate early‐stage ESCC patients from controls in both the training cohort and in the validation cohort . Driven by the fact that autoantibodies against tumor‐associated antigens are present in many types of cancers, and may function as biomarkers for early cancer diagnosis, 149 patients with ESCC, 34 with early ESCC, and 98 HC were subjected to a study analyzing the levels of the circulating autoantibodies against Fascin.…”

Autoantibodies against tumor-associated antigens as one class of serological markers

“…Например, стрессиндуцированный фосфопротеин 1 (STIP1), представитель семейства шаперонов, также известный как НОР, р60 и STI, распознается иммунной системой как ОААГ, вызывая гуморальный иммунный ответ в виде ААТ [36]. Повышенная экспрессия STIP1 была показана в тканях ряда злокачественных опухолей: раке поджелудочной железы, печени, РЯ и колоректальном раке [35]. Кроме этого, обнаружена связь повышенной экспрессии STIP1 с низкой выживаемостью онкологических больных [37,38].…”

“…Кроме этого, обнаружена связь повышенной экспрессии STIP1 с низкой выживаемостью онкологических больных [37,38]. Повышенные уровни ААТ к STIP1 обнаружены в сыворотке крови больных РЯ и РП [35,37]. Y. W. Xu и соавт.…”

“…Y. W. Xu и соавт. при валидации теста на ААТ к STIP1 сообщили о достаточно высокой (для начальных стадий) чувствительности теста на основе АТТ к STIP1 в обучающей когорте (35,7 %) и валидируемой когорте (38,5 %) больных плоскоклеточным РП (ПРП) при специфичности 90 % [35]. Вместе с тем причины повышения ААТ к белку-шаперону STIP1 остаются не изученными.…”