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High FAK combined with low JWA expression: clinical prognostic and predictive role for adjuvant fluorouracil–leucovorin–oxaliplatin treatment in resectable gastric cancer patients

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Abstract

Background

The multifunctional protein JWA was previously identified as a novel regulator of focal adhesion kinase (FAK/PTK2) in suppressing cancer cell adhesion, invasion and metastasis. JWA is downregulated in gastric cancer (GC) and a prognostic and predictive biomarker for resectable GC. However, the value of FAK combined with JWA for GC patients as a biomarker has not been studied. Here we evaluated the roles of FAK alone and combined with JWA in GC patients treated with surgery alone or combined with adjuvant platinum-based chemotherapy.

Methods

Two tissue microarrays were constructed of specimens from resected GC (n = 709 in total) for detection of FAK and JWA expression by immunohistochemistry. Correlations between both proteins and clinicopathological features as well as prognostic and predictive values were evaluated.

Results

Compared with adjacent non-cancerous tissues, FAK protein levels were remarkably up-regulated in GC lesions (P < 0.001). High FAK alone or combined with low JWA expression significantly correlated with worse overall survival (OS) (both P < 0.001 in two cohorts). Simultaneously, JWA plus FAK expression was a more valuable prognostic biomarker than JWA or FAK alone. Moreover, the patients with high FAK only or combined with low JWA had significant benefit from adjuvant fluorouracil–leucovorin–oxaliplatin (FLO) therapy compared with those with surgery alone (P = 0.003); however, the cases with adjuvant fluorouracil–leucovorin–cisplatin (FLP) therapy did not show these effects.

Conclusion

FAK plus JWA may serve as a more prognostic and predictive biomarker for GC than each separately with a potential clinical application.

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Acknowledgments

This study was supported in part by the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China (30930080, 81161120537), and the Foundation of Cancer Center of Nanjing Medical University (08ZLKF08).

Conflict of interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People’s Republic of China

    Yansu Chen, Xiaowei Xia, Shouyu Wang, Xuming Wu, Jianbing Zhang, Aiping Li & Jianwei Zhou

  2. Department of Pathology, Nantong Cancer Hospital, 30 North Tongyang Road, Pingchao, Nantong, 226361, Jiangsu Province, People’s Republic of China

    Xuming Wu, Jianbing Zhang, Song He & Fulin Qiang

  3. Department of Oncology, Yixing People’s Hospital, 75 West Tongzhenguan Road, Yixing, 214200, Jiangsu Province, People’s Republic of China

    Yan Zhou & Yongfei Tan

  4. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491, Trondheim, Norway

    Oluf Dimitri Røe

  5. Cancer Clinic, Levanger Hospital, Nord-Trøndelag Health Trust, 7600, Levanger, Norway

    Oluf Dimitri Røe

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  1. Yansu Chen
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Correspondence to Jianwei Zhou.

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Chen, Y., Xia, X., Wang, S. et al. High FAK combined with low JWA expression: clinical prognostic and predictive role for adjuvant fluorouracil–leucovorin–oxaliplatin treatment in resectable gastric cancer patients. J Gastroenterol 48, 1034–1044 (2013). https://doi.org/10.1007/s00535-012-0724-7

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  • DOI: https://doi.org/10.1007/s00535-012-0724-7

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