TY - JOUR
T1 - Insulin-like growth factor-1 receptor expression and disease recurrence and survival in patients with resected pancreatic ductal adenocarcinoma
AU - Du, Chunxia
AU - Silva, Annacarolina da
AU - Morales-Oyarvide, Vicente
AU - Costa, Andressa Dias
AU - Kozak, Margaret M.
AU - Dunne, Richard F.
AU - Rubinson, Douglas A.
AU - Perez, Kimberly
AU - Masugi, Yohei
AU - Hamada, Tsuyoshi
AU - Brais, Lauren K.
AU - Yuan, Chen
AU - Babic, Ana
AU - Ducar, Matthew D.
AU - Thorner, Aaron R.
AU - Aguirre, Andrew
AU - Kulke, Matthew H.
AU - Ng, Kimmie
AU - Clancy, Thomas E.
AU - Findeis-Hosey, Jennifer J.
AU - Chang, Daniel T.
AU - Hornick, Jason L.
AU - Fuchs, Charles S.
AU - Ogino, Shuji
AU - Koong, Albert C.
AU - Hezel, Aram F.
AU - Wolpin, Brian M.
AU - Nowak, Jonathan A.
N1 - Funding Information:
This study was supported by the following grants: NIH K07 CA148894 (to K. Ng); NCI R35 CA197735 (to S. Ogino); MyBlueDots Fund (to A.C. Koong); and Hale Center for Pancreatic Cancer Research, NIH/NCI U01 CA210171, NIH/NCI P50 CA127003, Lustgarten Foundation, Pancreatic Cancer Action Network, Noble Effort Fund, Wexler Family Fund, and Promises for Purple (to B.M. Wolpin).
Funding Information:
C.S. Fuchs has ownership interest (including patents) in CytomX Therapeutics, Entrinsic Health, and Evolveimmune Therapeutics and is a consultant for Agios, Bain Capital, CytomX Therapeutics, Daiichi Sankyo, Eli Lilly, Entrinsic Health, Genentech, Merck, Taiho, and Unum Therapeutics. A.C. Koong has ownership interest (including patents) in Aravive, Inc. B.M. Wolpin reports receiving commercial research grants from Celgene and Eli Lilly, and reports receiving speakers bureau honoraria from Celgene, GRAIL, BioLineRx, and G1 Therapeutics. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
R.F. Dunne is a consultant for Exelixis, Inc. A. Aguirre is a consultant for Merck, Arrakis Therapeutics, and Oncorus. K. Ng reports receiving commercial research grants from Celgene, Gilead, and Revolution Medicines. J.J. Findeis-Hosey reports receiving speakers bureau honoraria from College of American Pathologists.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/8
Y1 - 2020/8
N2 - Background: Insulin-like growth factor-1 receptor (IGF1R) signaling is important in pancreatic ductal adenocarcinoma (PDAC) biology, but little is known regarding IGF1R expression and patient characteristics and outcomes. Methods: In 365 patients with resected PDAC, we evaluated IGF1R protein expression using IHC on whole-slide sections and IGF1R genomic status using next-generation sequencing. Associations of IGF1R expression, measured by H-scores incorporating staining intensity and proportion of positive tumor cells, with disease-free survival (DFS) and overall survival (OS) were evaluated in 317 and 321 patients, respectively, using Cox regression adjusting for known prognostic factors. Results: Higher IGF1R expression in tumor cells was associated with worse DFS comparing highest versus lowest expression tertiles [median DFS, 10.8 vs. 16.1 months; adjusted hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.24–2.44; Ptrend ¼ 0.002] and worse OS (median OS, 17.4 vs. 25.8 months; HR, 1.39; 95% CI, 1.00–1.92; Ptrend ¼ 0.046). The association between high IGF1R expression and reduced DFS was identified primarily among patients with a preoperative body mass index ≥25 kg/m2 (HR, 4.27; 95% CI, 2.03–8.96, comparing extreme tertiles; Pinteraction ¼ 0.032). KRAS-mutant tumors had greater IGF1R expression, and IGF1R expression in tumor epithelium was inversely correlated with that in stromal cells. Mutations in IGF1R were infrequent, and no overt loss-of-function alterations were identified. Higher IGF1R expression was modestly associated with higher gene copy number (Pearson correlation coefficient ¼ 0.26, P < 0.001). Conclusions: Higher IGF1R protein expression was associated with worse patient outcomes in resected PDAC. Impact: IGF1R expression in PDAC represents a potential biomarker to guide patient selection for more aggressive, multidrug regimens in the adjuvant setting.
AB - Background: Insulin-like growth factor-1 receptor (IGF1R) signaling is important in pancreatic ductal adenocarcinoma (PDAC) biology, but little is known regarding IGF1R expression and patient characteristics and outcomes. Methods: In 365 patients with resected PDAC, we evaluated IGF1R protein expression using IHC on whole-slide sections and IGF1R genomic status using next-generation sequencing. Associations of IGF1R expression, measured by H-scores incorporating staining intensity and proportion of positive tumor cells, with disease-free survival (DFS) and overall survival (OS) were evaluated in 317 and 321 patients, respectively, using Cox regression adjusting for known prognostic factors. Results: Higher IGF1R expression in tumor cells was associated with worse DFS comparing highest versus lowest expression tertiles [median DFS, 10.8 vs. 16.1 months; adjusted hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.24–2.44; Ptrend ¼ 0.002] and worse OS (median OS, 17.4 vs. 25.8 months; HR, 1.39; 95% CI, 1.00–1.92; Ptrend ¼ 0.046). The association between high IGF1R expression and reduced DFS was identified primarily among patients with a preoperative body mass index ≥25 kg/m2 (HR, 4.27; 95% CI, 2.03–8.96, comparing extreme tertiles; Pinteraction ¼ 0.032). KRAS-mutant tumors had greater IGF1R expression, and IGF1R expression in tumor epithelium was inversely correlated with that in stromal cells. Mutations in IGF1R were infrequent, and no overt loss-of-function alterations were identified. Higher IGF1R expression was modestly associated with higher gene copy number (Pearson correlation coefficient ¼ 0.26, P < 0.001). Conclusions: Higher IGF1R protein expression was associated with worse patient outcomes in resected PDAC. Impact: IGF1R expression in PDAC represents a potential biomarker to guide patient selection for more aggressive, multidrug regimens in the adjuvant setting.
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U2 - 10.1158/1055-9965.EPI-19-1315
DO - 10.1158/1055-9965.EPI-19-1315
M3 - Article
C2 - 32467349
AN - SCOPUS:85089127767
VL - 29
SP - 1586
EP - 1595
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 8
ER -