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Loss of PTEN expression as a predictor of resistance to anti-EGFR monoclonal therapy in metastatic colorectal cancer: evidence from retrospective studies

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Abstract

Purpose

To investigate the predictive value of loss of PTEN expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR monoclonal therapy.

Methods

Studies were systematically identified to investigate the relationship between PTEN expression and clinical outcome in mCRC patients treated with anti-EGFR MoAbs. Clinical outcomes included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated using a fixed-effects model or a random-effects model according to the heterogeneity between the studies.

Results

A total of 852 patients were included in the final meta-analysis. The rate of loss of PTEN expression was 28.4 % (242/852). The overall pooled RR for ORR was 0.413 (95 % confidence intervals (CI), 0.177–0.965) when patients with loss of PTEN expression were compared with those with normal PTEN expression. Anti-EGFR monoclonal therapy resulted in improved PFS (HR, 0.466; 95 % CI, 0.292–0.640) and OS (HR, 0.689 [95 % CI, 0.482–0.896]) in patients unselected by KRAS mutation with normal PTEN expression over loss of PTEN expression. A better prognosis, as reflected by PFS (HR, 0.344; 95 % CI, 0.154–0.533) and OS (HR, 0.544; 95 % CI, 0.285–0.803), was observed in wild-type KRAS patients with normal PTEN expression versus loss of expression.

Conclusions

Loss of expression of PTEN is a potential biomarker for resistance to anti-EGFR monoclonal therapy, particularly in mCRC patients with KRAS wild type.

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Acknowledgments

This work was supported by a grant from the National Science Found of China (30830055) and the Ministry of Public Health, China (No. 200802094).

Conflict of interest

No company had any input into or influence on the design, analysis, interpretation, or content of this manuscript. There are no conflicts of interest with any of the authors.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao-Tong University School of Medicine Renji Hospital, 145 Middle Shandong Rd, Shanghai, 200001, China

    Zhen-Hua Wang, Qin-Yan Gao & Jing-Yuan Fang

  2. Key Laboratory of Gastroenterology and Hepatology, Ministry of Health (Shanghai Jiao-Tong University), 145 Middle Shandong Rd, Shanghai, 200001, China

    Zhen-Hua Wang, Qin-Yan Gao & Jing-Yuan Fang

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  1. Zhen-Hua Wang
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Correspondence to Jing-Yuan Fang.

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Wang, ZH., Gao, QY. & Fang, JY. Loss of PTEN expression as a predictor of resistance to anti-EGFR monoclonal therapy in metastatic colorectal cancer: evidence from retrospective studies. Cancer Chemother Pharmacol 69, 1647–1655 (2012). https://doi.org/10.1007/s00280-012-1886-y

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