Abstract
Simple SummaryConventional serum markers such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and tissue polypeptide antigen (TPA) have a low sensitivity in predicting the prognosis of locoregional esophageal squamous cell carcinoma cell (ESCC). In our clinical study, we found high serum elafin to be an independent outcome predictor for stage I-IIIA ESCC, considering T, N, overall stage, and treatment. In vitro experiments showed that adding recombinant elafin drove ESCC cell proliferation, migration and invasion, while shRNA attenuated elafin levels, abrogating those effects. Our results suggested serum elafin might be a noninvasive biomarker to predict the outcome of locoregional ESCC and could potentially be used as a therapeutic target.Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor known to have locally advanced and metastatic features which cause a dismal prognosis. We sought to determine whether elafin, a non-invasive and secretory small-molecule marker, could be used to predict prognosis in locoregional ESCC patients in human and in vitro studies. In our human study, 119 subjects were identified as having incident and pathologically-proved ESCC with stage I-IIIA tumors from southern Taiwan between 2000 and 2016. We measured their serum elafin levels at baseline and followed them until the date of cancer death or until January 2020, the end of this study. Those with high serum elafin levels were found to have a 1.99-fold risk (95% confidence interval: 1.17–3.38) shorter survival than those who did not. In our in vitro experiments, elevated elafin levels were found to drive ESCC cell proliferation, migration and invasion, while attenuation of elafin level by shRNA abrogated those effects. We concluded that elafin promotes ESCC motility and invasion and leads to a worse clinical prognosis in ESCC patients without distant metastasis.
Highlights
Esophageal cancer was the seventh most prevalent cancer and the sixth most important cause of cancer mortality worldwide in 2018 [1]
The 119 patients with stage I-IIIA Esophageal squamous cell carcinoma (ESCC) had an average age of 57.83 years old and were predominantly male (95.3%) (Table 1)
Some studies have found that elafin can drive poor prognosis in patients with breast and ovarian cancers [12,13,14], but there has been no study of its effect on ESCC prognosis, and only a very few studies have examined its role on ESCC risk [5]
Summary
Esophageal cancer was the seventh most prevalent cancer and the sixth most important cause of cancer mortality worldwide in 2018 [1]. Known as peptidase inhibitor 3 (PI3) or skin-derived anti-leukoproteinase (SKALP), is a secretory small molecule [5,6] It is produced by epithelial cells in response to macrophage infiltration, the release of proteolytic enzymes, and disruption of epithelial integrity [7,8,9]. Elafin mRNA or protein is known to be overexpressed in cancer tissues arising from normal squamous epithelium of head and neck, esophagus, and bronchi, when compared to adjacent normal tissues [5,6,10], there have been no studies, to our best knowledge, to examine the possible predictive or prognostic ability of its expression in locoregional ESCC patients (stage I-IIIA). We performed an in vitro study to measure the effect of elafin expression on cell motility and invasion
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