Impact of Insulin-like Growth Factor System on the Progression and Survival of Gastric Adenocarcinoma

Author:

Tsai Kun-Feng1,Shun Chia-Tung2,Fang Yu-Jen3,Hong Tzu-Chan2,Chen Chieh-Chang2,Chen Chih-Cheng4,Wu Yi-Ling4,Lin Jaw-Town4,Lai I-Rue2,Wu Ming-Shiang2,Liou JyhMing5

Affiliation:

1. National Taiwan University

2. National Taiwan University Hospital

3. National Taiwan University Hospital, Yun-Lin Branch

4. E-Da Hospital

5. National Taiwan University Cancer Center,Taipei

Abstract

Abstract

Background A comprehensive study on the impact of the insulin-like growth (IGF) signaling system in the progression of gastric cancer is lacking. Therefore, we conducted a hospital-based cohort study to comprehensively assess the influence of the IGF family, including IGF1, IGF2, and IGF binding proteins 1, 2, and 3, on gastric cancer (GC). Method Expression levels of IGF1, IGF2, IGF IR, IIR, and IGFBP1-3 in GC were determined by immunohistochemistry staining in 28 patients. Plasma levels of IGF1, IGF2, and IGFBP1-3 were measured using immunoradiometric assay or ELISA in the training cohort. Plasma IGFBP2 levels were determined in the validation cohort, consisting of 255 GC patients. Expression of IGFBP2 in gastric cancer tissues was assessed in 484 GC patients. Overall survival (OS) and relapse-free survival (RFS) based on plasma levels of IGF proteins and expression of IGFBP2 in GC tissues were analyzed. Result IGFBP2 was expressed in tumors (92.8%, 26/28) and non-tumor tissues (85.7%, 24/28) of GC patients, with low expression rates for other biomarkers. Higher plasma IGFBP2 levels in the training cohort (N = 142) were associated with worse OS (p = 0.0009) and RFS (p = 0.0001). Cox regression analysis confirmed that higher plasma IGFBP2 levels predicted a worse prognosis (HR: 1.51; 95% CI: 1.19–1.92; p = 0.001), whereas IGF1, IGF2, IGFBP1, and IGFBP3 did not. In the validation cohort (N = 255), higher plasma IGFBP2 levels again correlated with worse OS (p = 0.00001) and RFS (p = 0.0001). Conclusion IGFBP2, but not other members of the IGF system, correlated with the disease progression and survival of gastric cancer.

Publisher

Springer Science and Business Media LLC

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