High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial

Shu Ling Pen; Yan Shen Shan; Chin Fu Hsiao; Tsang Wu Liu; Jen Shi Chen; Ching Liang Ho; Wen Chi Chou; Ruey Kuen Hsieh; Li Tzong Chen; Hui Ju Ch'ang

doi:10.1016/j.radonc.2021.02.037

High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial

Shu Ling Pen
, Yan Shen Shan
, Chin Fu Hsiao
, Tsang Wu Liu
, Jen Shi Chen
, Ching Liang Ho
, Wen Chi Chou
, Ruey Kuen Hsieh
, Li Tzong Chen
, Hui Ju Ch'ang^*

^*此作品的通信作者

醫學系

National Cheng Kung University
National Health Research Institutes Taiwan
Chang Gung University
Triservice General Hospital Taiwan
Mackay Memorial Hospital Taiwan
Kaohsiung Medical University
Taipei Medical University

研究成果: 期刊稿件 › 文章 › 同行評審

10 引文斯高帕斯（Scopus）

摘要

Purpose: Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.

原文	英語
頁（從 - 到）	146-154
頁數	9
期刊	Radiotherapy and Oncology
卷	158
DOIs	https://doi.org/10.1016/j.radonc.2021.02.037
出版狀態	已出版 - 05 2021

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Publisher Copyright:
© 2021 Elsevier B.V.

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10.1016/j.radonc.2021.02.037

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Pen, S. L., Shan, Y. S., Hsiao, C. F., Liu, T. W., Chen, J. S., Ho, C. L., Chou, W. C., Hsieh, R. K., Chen, L. T., & Ch'ang, H. J. (2021). High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial. Radiotherapy and Oncology, 158, 146-154. https://doi.org/10.1016/j.radonc.2021.02.037

@article{21ad875e755c42429f3e7e1fe69204ef,

title = "High expression of kr{\"u}ppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial",

abstract = "Purpose: Our previous studies have demonstrated that Kr{\"u}ppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.",

keywords = "Chemoradiotherapy, Kr{\"u}ppel-like factor 10, Pancreatic adenocarcinoma, Runx3, Smad4",

author = "Pen, \{Shu Ling\} and Shan, \{Yan Shen\} and Hsiao, \{Chin Fu\} and Liu, \{Tsang Wu\} and Chen, \{Jen Shi\} and Ho, \{Ching Liang\} and Chou, \{Wen Chi\} and Hsieh, \{Ruey Kuen\} and Chen, \{Li Tzong\} and Ch'ang, \{Hui Ju\}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

year = "2021",

month = may,

doi = "10.1016/j.radonc.2021.02.037",

language = "英语",

volume = "158",

pages = "146--154",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Pen, SL, Shan, YS, Hsiao, CF, Liu, TW, Chen, JS, Ho, CL, Chou, WC, Hsieh, RK, Chen, LT & Ch'ang, HJ 2021, 'High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial', Radiotherapy and Oncology, 卷 158, 頁 146-154. https://doi.org/10.1016/j.radonc.2021.02.037

TY - JOUR

T1 - High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma

T2 - From a randomized phase III trial

AU - Pen, Shu Ling

AU - Shan, Yan Shen

AU - Hsiao, Chin Fu

AU - Liu, Tsang Wu

AU - Chen, Jen Shi

AU - Ho, Ching Liang

AU - Chou, Wen Chi

AU - Hsieh, Ruey Kuen

AU - Chen, Li Tzong

AU - Ch'ang, Hui Ju

PY - 2021/5

Y1 - 2021/5

N2 - Purpose: Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.

AB - Purpose: Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.

KW - Chemoradiotherapy

KW - Krüppel-like factor 10

KW - Pancreatic adenocarcinoma

KW - Runx3

KW - Smad4

UR - https://www.scopus.com/pages/publications/85102301521

U2 - 10.1016/j.radonc.2021.02.037

DO - 10.1016/j.radonc.2021.02.037

M3 - 文章

C2 - 33667587

AN - SCOPUS:85102301521

SN - 0167-8140

VL - 158

SP - 146

EP - 154

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -

High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial

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