Abstract
Stanniocalcin-1 (STC1) is a secreted glycoprotein hormone and highly expressed in various types of human malignancies. Although evidence points to the role of STC1 in human cancers, the clinical significance of STC1 expression in esophageal cancer has not been well established. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry were performed to assess the expression of STC1 in the cancer cell line TE8 and esophageal cancer tissues from 229 esophageal squamous cell carcinomas (ESCC). Surgically-resected tissue sections were immunostained for potential regulators of STC1 expression, hypoxia-inducible factor-1α (HIF-1α) and p53. Marked increase in STC1 mRNA and protein expression was noted in TE8 cells cultured under hypoxic conditions. Overexpression of STC1 mRNA was noted in ESCC tumors compared to normal counterparts. Positive immunohistochemical staining for STC1 protein was observed in 38.9% of patients, and correlated significantly with advanced pT status (P=0.019), poor prognosis [overall survival (P<0.0006) and disease-free survival (P<0.0002) of ESCC patients who had undergone curative surgery]. Positive staining for HIF-1α and p53 proteins in ESCC did not correlate with STC1 expression. The results showed marked induction of STC1 expression under hypoxia in cultured cells and in esophageal cancer cells and that overexpression of STC1 was an independent prognostic factor in patients with esophageal cancer who had undergone curative surgery. STC1 is a potentially useful biomarker for ESCC treatment.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the gastrointestinal tract [1,2]
We previously reported that STC1 was expressed in various human cancer cell lines as well as in human colorectal, breast, stomach, esophageal, biliary tract, and liver tumors [8]
We reported enhanced expression of STC1 in tumor tissues compared to the background normal tissues
Summary
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the gastrointestinal tract [1,2]. Stanniocalcin-1 (STC1) is an anti-hypercalcemic hormone, which was discovered in the corpuscles of Stannius (an endocrine gland unique to bony fish) [5]. In 1995, Chang et al reported the isolation of the human counterpart of STC1, which was highly homologous to the fish hormone [6]. The human STC1 cDNA was cloned as a DNA fragment, whose expression level was different in SV40-transfected immortalized human fibroblast cells compared to mortal ones, indicating that STC1 might play a role in human cell immortalization [6]. STC2, a STC1 paralog, was identified following searching of the expressed sequence tag (EST) databases for STC1-related sequences [7]. Both STCs are expressed in a variety of human tissues, including endocrine glands and hormone responsive organs
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