Krüppel-like factor 10 expression as a prognostic indicator for pancreatic adenocarcinoma

Vincent H S Chang, Pei Yi Chu, Shu-Ling Peng, Tsui Lien Mao, Yan-Shen Shan, Ching Fang Hsu, Chun Yu Lin, Kelvin K C Tsai, Winston C Y Yu, Hui Ju Ch'Ang

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Abstract

Deregulation of transforming growth factor (TGF)-β function is a common feature of pancreatic cancer, rendering these cancers unresponsive to TGF-β-stimulated growth inhibition. Recent findings have supported a primary role for Krüppel-like factor 10 (KLF10) as an important transcription factor involved in mediating TGF-β1 signaling. The aim of this study was to evaluate the correlation between KLF10 expression and the clinical and pathologic features of pancreatic cancer. Tissue specimens from patients with pancreatic adenocarcinoma were retrospectively collected for immunohistochemical analysis. To demonstrate that Klf10 expression was primarily regulated by methylation status, the Klf10 promoter was examined by methylation-specific PCR using a pancreatic cancer cell line (Panc-1). DNA methyltransferase (DNMT) inhibitor and small-interfering RNA depletion of DNMT genes were used to reverse KLF10 expression in the Panc-1 cells. In parallel, DNMT1 expression was evaluated in the pancreatic cancer tissue specimens. In 95 pancreatic cancer tissue specimens, KLF10 expression was inversely correlated with pancreatic cancer stage (P = 0.01). Multivariable analysis revealed that, in addition to the presence of distant metastasis at diagnosis (P = 0.001 and 0.001, respectively), KLF10 was another independent prognostic factor related to progression-free and overall survival (P = 0.018 and 0.037, respectively). The loss of KLF10 expression in advanced pancreatic cancer is correlated with altered methylation status, which seems to be regulated by DNMT1. Our results suggest that KLF10 is a potential clinical predictor for progression of pancreatic cancer.

Original languageEnglish
Pages (from-to)423-430
Number of pages8
JournalAmerican Journal of Pathology
Volume181
Issue number2
DOIs
Publication statusPublished - 2012 Aug 1

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Pancreatic Neoplasms
Adenocarcinoma
Transforming Growth Factors
Methylation
Methyltransferases
DNA
Small Interfering RNA
Disease-Free Survival
Transcription Factors
Neoplasm Metastasis
Cell Line
Polymerase Chain Reaction
Growth
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Chang, Vincent H S ; Chu, Pei Yi ; Peng, Shu-Ling ; Mao, Tsui Lien ; Shan, Yan-Shen ; Hsu, Ching Fang ; Lin, Chun Yu ; Tsai, Kelvin K C ; Yu, Winston C Y ; Ch'Ang, Hui Ju. / Krüppel-like factor 10 expression as a prognostic indicator for pancreatic adenocarcinoma. In: American Journal of Pathology. 2012 ; Vol. 181, No. 2. pp. 423-430.
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Krüppel-like factor 10 expression as a prognostic indicator for pancreatic adenocarcinoma. / Chang, Vincent H S; Chu, Pei Yi; Peng, Shu-Ling; Mao, Tsui Lien; Shan, Yan-Shen; Hsu, Ching Fang; Lin, Chun Yu; Tsai, Kelvin K C; Yu, Winston C Y; Ch'Ang, Hui Ju.

In: American Journal of Pathology, Vol. 181, No. 2, 01.08.2012, p. 423-430.

Research output: Contribution to journalArticle

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AU - Chu, Pei Yi

AU - Peng, Shu-Ling

AU - Mao, Tsui Lien

AU - Shan, Yan-Shen

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