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Purpose <p>Cystatin SA (CST2) is a cysteine protease inhibitor that is overexpressed in several malignancies; however, its involvement in esophageal squamous cell carcinoma (ESCC) has yet to be investigated. This study evaluates CST2 expression, its association with clinicopathological parameters, and its prognostic significance in ESCC. We further investigate the biological functions of CST2 to assess CST2 impact on tumor progression and its potential as a prognostic marker.</p> Methods <p>CST2 expression was quantified in 16 ESCC cell lines and 165 paired tumor and adjacent non-cancerous tissues using quantitative reverse-transcription PCR (qRT-PCR). siRNA-mediated CST2 knockdown assays were performed to assess cellular functions in vitro and in vivo. Associations between CST2 expression and clinicopathological features, recurrence patterns, and survival outcomes, including disease-specific survival (DSS) and disease-free survival (DFS), were analyzed using statistical methods.</p> Results <p>CST2 mRNA levels were significantly elevated in ESCC tissues compared to normal mucosa. Knockdown of CST2 reduced proliferation, migration, and invasion in vitro, while in vivo models demonstrated smaller tumor volumes in CST2 knockdown groups compared to controls. High CST2 expression correlated with worse DSS and DFS. Multivariable analysis confirmed high CST2 expression as an independent prognostic factor for DSS.</p> Conclusion <p>CST2 plays a critical role in ESCC pathogenesis and progression. Its overexpression is associated with poor clinical outcomes, suggesting CST2 as a potential prognostic biomarker for recurrence and survival in ESCC.</p>

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The role of CST2 in the pathogenesis and prognosis of esophageal squamous cell carcinoma

  • 期刊论文

  • 发表日期：

    2025年4月21日

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  • Flor Esther Garza Martinez,
  • Mitsuro Kanda,
  • Yusuke Sato,
  • Haote Zhu,
  • Tuvshin Bayasgalan,
  • Mohammad Hussain Hamrah,
  • Dai Shimizu,
  • Haruyoshi Tanaka,
  • Shinichi Umeda,
  • Norifumi Hattori,
  • Masamichi Hayashi,
  • Chie Tanaka,
  • Goro Nakayama,
  • Yasuhiro Kodera

摘要

Purpose

Cystatin SA (CST2) is a cysteine protease inhibitor that is overexpressed in several malignancies; however, its involvement in esophageal squamous cell carcinoma (ESCC) has yet to be investigated. This study evaluates CST2 expression, its association with clinicopathological parameters, and its prognostic significance in ESCC. We further investigate the biological functions of CST2 to assess CST2 impact on tumor progression and its potential as a prognostic marker.

Methods

CST2 expression was quantified in 16 ESCC cell lines and 165 paired tumor and adjacent non-cancerous tissues using quantitative reverse-transcription PCR (qRT-PCR). siRNA-mediated CST2 knockdown assays were performed to assess cellular functions in vitro and in vivo. Associations between CST2 expression and clinicopathological features, recurrence patterns, and survival outcomes, including disease-specific survival (DSS) and disease-free survival (DFS), were analyzed using statistical methods.

Results

CST2 mRNA levels were significantly elevated in ESCC tissues compared to normal mucosa. Knockdown of CST2 reduced proliferation, migration, and invasion in vitro, while in vivo models demonstrated smaller tumor volumes in CST2 knockdown groups compared to controls. High CST2 expression correlated with worse DSS and DFS. Multivariable analysis confirmed high CST2 expression as an independent prognostic factor for DSS.

Conclusion

CST2 plays a critical role in ESCC pathogenesis and progression. Its overexpression is associated with poor clinical outcomes, suggesting CST2 as a potential prognostic biomarker for recurrence and survival in ESCC.