High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT.

Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (G...

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Publicado en:Current Oncology Vol. 28; no. 4; pp. 2373 - 2385
Autores principales: Tzu-Ju Chen, Yu-Feng Tian, Chia-Lin Chou, Ti-Chun Chan, Hong-Lin He, Wan-Shan Li, Hsin-Hwa Tsai, Chien-Feng Li, Hong-Yue Lai
Formato: Journal Article
Publicado: MDPI Aug2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Aug2021
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      pub: MDPI
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        atl: High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT.
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        au:
          Tzu-Ju Chen
          Yu-Feng Tian
          Chia-Lin Chou
          Ti-Chun Chan
          Hong-Lin He
          Wan-Shan Li
          Hsin-Hwa Tsai
          Chien-Feng Li
          Hong-Yue Lai
        affil: Department of Pathology, Chi Mei Medical Center, Tainan 710, Taiwan
      sug:
      ab: Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p < 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p < 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p < 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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