Insulin-like growth factor-1 receptor expression and disease recurrence and survival in patients with resected pancreatic ductal adenocarcinoma

Chunxia Du, Annacarolina da Silva, Vicente Morales-Oyarvide, Andressa Dias Costa, Margaret M. Kozak, Richard F. Dunne, Douglas A. Rubinson, Kimberly Perez, Yohei Masugi, Tsuyoshi Hamada, Lauren K. Brais, Chen Yuan, Ana Babic, Matthew D. Ducar, Aaron R. Thorner, Andrew Aguirre, Matthew H. Kulke, Kimmie Ng, Thomas E. Clancy, Jennifer J. Findeis-HoseyDaniel T. Chang, Jason L. Hornick, Charles S. Fuchs, Shuji Ogino, Albert C. Koong, Aram F. Hezel, Brian M. Wolpin, Jonathan A. Nowak

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1586-1595
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume29
Issue number8
DOIs
Publication statusPublished - 2020 Aug

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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