Clinical Significance of IGF1R Gene Expression in Patients with Stage II/III Gastric Cancer Who Receive Curative Surgery and Adjuvant Chemotherapy with S-1

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2015 Sep 5

PMID 26337161

Citations 7

Authors

Koji Numata

Takashi Oshima

Kentaro Sakamaki

Kazue Yoshihara

Toru Aoyama

Tsutomu Hayashi

Takanobu Yamada

Tsutomu Sato

Haruhiko Cho

Manabu Shiozawa

Takaki Yoshikawa

Yasushi Rino

Chikara Kunisaki

Makoto Akaike

Toshio Imada

Munetaka Masuda

Affiliations

Soon will be listed here.

Abstract

Purpose: Curative resection and adjuvant chemotherapy is the standard treatment for Stage II/III gastric cancer, and S-1 is widely used for adjuvant chemotherapy. The type 1 insulin-like growth factor receptor (IGF1R) is involved in cell proliferation and prevention of apoptosis in many tumors. We evaluated the relative expression of the IGF1R gene to determine whether such expression correlates with outcomes in patients with Stage II/III gastric cancer.

Methods: We measured the expression levels of the IGF1R gene in specimens of cancer and adjacent normal mucosa obtained from 134 patients with Stage II/III gastric cancer who received curative resection and adjuvant chemotherapy with S-1. We then evaluated whether the IGF1R gene expression levels correlate with clinicopathological characteristics and outcomes.

Results: IGF1R mRNA expression levels tended to be higher in cancer tissue than in the normal adjacent mucosa (P = 0.078). Multivariate analysis showed that high IGF1R gene expression was a significant independent predictor of poor survival in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1 (HR 3.681, P = 0.007). The overall survival rate was significantly lower in patients with high IGF1R gene expression than in those with low expression (P = 0.012).

Conclusions: IGF1R overexpression is considered a useful independent predictor of outcomes in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1.

Citing Articles

SphK1 functions downstream of IGF-1 to modulate IGF-1-induced EMT, migration and paclitaxel resistance of A549 cells: A preliminary in vitro study.

Wu X, Wu Q, Zhou X, Huang J J Cancer. 2019; 10(18):4264-4269.

PMID: 31413745 PMC: 6691691. DOI: 10.7150/jca.32646.

Molecular Signatures of the Insulin-like Growth Factor 1-mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers.

Cevenini A, Orru S, Mancini A, Alfieri A, Buono P, Imperlini E Int J Mol Sci. 2018; 19(8).

PMID: 30111747 PMC: 6122069. DOI: 10.3390/ijms19082411.

Insulin-like Growth Factor 1 Receptor Expression in Advanced Non-small-cell Lung Cancer and its Impact on Overall Survival.

Humar M, Kern I, Vlacic G, Hadzic V, Cufer T Radiol Oncol. 2017; 51(2):195-202.

PMID: 28740455 PMC: 5514660. DOI: 10.1515/raon-2017-0020.

Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway.

Ren J, Seth P, Ye H, Guo K, Hanai J, Husain Z Sci Rep. 2017; 7(1):4537.

PMID: 28674429 PMC: 5495754. DOI: 10.1038/s41598-017-04626-4.

IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights.

Li H, Batth I, Qu X, Xu L, Song N, Wang R Mol Cancer. 2017; 16(1):6.

PMID: 28137302 PMC: 5282886. DOI: 10.1186/s12943-016-0576-5.

References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Alessi D, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P . Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 1996; 15(23):6541-51. PMC: 452479. View

Brodt P, Samani A, Navab R . Inhibition of the type I insulin-like growth factor receptor expression and signaling: novel strategies for antimetastatic therapy. Biochem Pharmacol. 2000; 60(8):1101-7. DOI: 10.1016/s0006-2952(00)00422-6. View

Furstenberger G, Senn H . Insulin-like growth factors and cancer. Lancet Oncol. 2002; 3(5):298-302. DOI: 10.1016/s1470-2045(02)00731-3. View

Ludovini V, Bellezza G, Pistola L, Bianconi F, Di Carlo L, Sidoni A . High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients. Ann Oncol. 2009; 20(5):842-9. DOI: 10.1093/annonc/mdn727. View

Mauras N, Attie K, Reiter E, Saenger P, Baptista J . High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc., Cooperative Study Group. J Clin Endocrinol Metab. 2000; 85(10):3653-60. DOI: 10.1210/jcem.85.10.6906. View

Long L, Rubin R, Baserga R, Brodt P . Loss of the metastatic phenotype in murine carcinoma cells expressing an antisense RNA to the insulin-like growth factor receptor. Cancer Res. 1995; 55(5):1006-9. View

Imsumran A, Adachi Y, Yamamoto H, Li R, Wang Y, Min Y . Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma. Carcinogenesis. 2006; 28(5):947-56. DOI: 10.1093/carcin/bgl247. View

Hilmi C, Larribere L, Giuliano S, Bille K, Ortonne J, Ballotti R . IGF1 promotes resistance to apoptosis in melanoma cells through an increased expression of BCL2, BCL-X(L), and survivin. J Invest Dermatol. 2007; 128(6):1499-505. DOI: 10.1038/sj.jid.5701185. View

10.

Dudek H, Datta S, Franke T, Birnbaum M, Yao R, Cooper G . Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 1997; 275(5300):661-5. DOI: 10.1126/science.275.5300.661. View

11.

Blakesley V, Stannard B, Kalebic T, Helman L, LeRoith D . Role of the IGF-I receptor in mutagenesis and tumor promotion. J Endocrinol. 1997; 152(3):339-44. DOI: 10.1677/joe.0.1520339. View

12.

Adachi Y, Li R, Yamamoto H, Min Y, Piao W, Wang Y . Insulin-like growth factor-I receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of matrilysin. Carcinogenesis. 2009; 30(8):1305-13. DOI: 10.1093/carcin/bgp134. View

13.

Hopkins A, Crowe P, Yang J . Effect of type 1 insulin-like growth factor receptor targeted therapy on chemotherapy in human cancer and the mechanisms involved. J Cancer Res Clin Oncol. 2010; 136(5):639-50. DOI: 10.1007/s00432-010-0792-0. View

14.

Mazumdar M, Smith A, Bacik J . Methods for categorizing a prognostic variable in a multivariable setting. Stat Med. 2003; 22(4):559-71. DOI: 10.1002/sim.1333. View

15.

Zha J, Harada H, Yang E, Jockel J, Korsmeyer S . Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 1996; 87(4):619-28. DOI: 10.1016/s0092-8674(00)81382-3. View

16.

Shiraishi T, Mori M, Yamagata M, Haraguchi M, Ueo H, Sugimachi K . Expression of insulin-like growth factor 2 mRNA in human gastric cancer. Int J Oncol. 1998; 13(3):519-23. DOI: 10.3892/ijo.13.3.519. View

17.

del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G . Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 1997; 278(5338):687-9. DOI: 10.1126/science.278.5338.687. View

18.

Pavelic K, Kolak T, Kapitanovic S, Radosevic S, Spaventi S, Kruslin B . Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R). J Pathol. 2003; 201(3):430-8. DOI: 10.1002/path.1465. View

19.

Weber M, Fottner C, Liu S, Jung M, Engelhardt D, Baretton G . Overexpression of the insulin-like growth factor I receptor in human colon carcinomas. Cancer. 2002; 95(10):2086-95. DOI: 10.1002/cncr.10945. View

20.

Valsecchi M, McDonald M, Brody J, Hyslop T, Freydin B, Yeo C . Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma. Cancer. 2011; 118(14):3484-93. DOI: 10.1002/cncr.26661. View