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- Academic Editor
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†These authors contributed equally.
Background: Esophageal squamous cell carcinoma (ESCC) is a highly
lethal tumor type, but studies on the ESCC tumor microenvironment are limited. We
found that cystatin SN (CST1) plays an important role in the ESCC tumor
microenvironment. CST1 has been reported to act as an oncogene in
multiple human cancers, but its clinical significance and underlying mechanism in
ESCC remain elusive. Methods: We performed ESCC gene expression
profiling with data from RNA-sequencing and public databases and found
CST1 upregulation in ESCC. Then, we assessed CST1 expression in
ESCC by RT‒qPCR and Western blot analysis. In addition, immunohistochemistry
(IHC) and enzyme-linked immunosorbent assay (ELISA) were used to estimate the
expression of CST1 in ESCC tissue and serum. Moreover, further
functional experiments were conducted to verify that the gain and loss of
CST1 in ESCC cell lines significantly influenced the proliferation and
metastasis of ESCC. Mass spectrometry, coimmunoprecipitation, and gelatin
zymography experiments were used to validate the interaction between
CST1 and matrix metalloproteinase 2 (MMP2) and the mechanism of CST1 influence on metastasis
in ESCC. Results: Here, we found that CST1 expression was
significantly elevated in ESCC tissues and serum. Moreover, compared with
patients with low CST1 expression, patients with high CST1
expression had a worse prognosis. Overall survival (OS) and disease-free survival
(DFS) were significantly unfavorable in the high CST1 expression
subgroup. Likewise, the CST1 level was significantly increased in ESCC
serum compared with healthy control serum, indicating that CST1 may be a
potential serum biomarker for diagnosis, with an area under the curve (AUC) =
0.9702 and p