Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy

Hayato Fujita, Kenoki Ouchida, Kazuhiro Mizumoto, Soichi Itaba, Tetsuhide Ito, Kohei Nakata, Jun Yu, Tadashi Kayashima, Ryota Sozaki, Tatsuro Tajiri, Tatsuya Manabe, Ohtsuka Takao, Masao Tanaka

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Abstract

Background Andaims: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. Materials And Methods: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P =.0067), low RRM2 (P =.003), and high GEM score (P =.0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P =.0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. Conclusions: Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC.

Original languageEnglish
Pages (from-to)807-817
Number of pages11
JournalNeoplasia
Volume12
Issue number10
DOIs
Publication statusPublished - Jan 1 2010

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gemcitabine
Adjuvant Chemotherapy
Pancreatic Neoplasms
Endoscopic Ultrasound-Guided Fine Needle Aspiration
Adenocarcinoma
Gene Expression
Drug Therapy
Paraffin
Formaldehyde
Messenger RNA
Reverse Transcription
Disease-Free Survival
Multivariate Analysis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Cancer Research

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Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. / Fujita, Hayato; Ouchida, Kenoki; Mizumoto, Kazuhiro; Itaba, Soichi; Ito, Tetsuhide; Nakata, Kohei; Yu, Jun; Kayashima, Tadashi; Sozaki, Ryota; Tajiri, Tatsuro; Manabe, Tatsuya; Takao, Ohtsuka; Tanaka, Masao.

In: Neoplasia, Vol. 12, No. 10, 01.01.2010, p. 807-817.

Research output: Contribution to journalArticle

Fujita, Hayato ; Ouchida, Kenoki ; Mizumoto, Kazuhiro ; Itaba, Soichi ; Ito, Tetsuhide ; Nakata, Kohei ; Yu, Jun ; Kayashima, Tadashi ; Sozaki, Ryota ; Tajiri, Tatsuro ; Manabe, Tatsuya ; Takao, Ohtsuka ; Tanaka, Masao. / Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. In: Neoplasia. 2010 ; Vol. 12, No. 10. pp. 807-817.
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abstract = "Background Andaims: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. Materials And Methods: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P =.0067), low RRM2 (P =.003), and high GEM score (P =.0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P =.0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. Conclusions: Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC.",
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T1 - Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy

AU - Fujita, Hayato

AU - Ouchida, Kenoki

AU - Mizumoto, Kazuhiro

AU - Itaba, Soichi

AU - Ito, Tetsuhide

AU - Nakata, Kohei

AU - Yu, Jun

AU - Kayashima, Tadashi

AU - Sozaki, Ryota

AU - Tajiri, Tatsuro

AU - Manabe, Tatsuya

AU - Takao, Ohtsuka

AU - Tanaka, Masao

PY - 2010/1/1

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N2 - Background Andaims: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. Materials And Methods: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P =.0067), low RRM2 (P =.003), and high GEM score (P =.0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P =.0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. Conclusions: Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC.

AB - Background Andaims: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. Materials And Methods: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P =.0067), low RRM2 (P =.003), and high GEM score (P =.0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P =.0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. Conclusions: Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC.

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