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Correlations of IGF-1R and COX-2 Expressions with Ras and BRAF Genetic Mutations, Clinicopathological Features and Prognosis of Colorectal Cancer Patients

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Pathology & Oncology Research

Abstract

This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RT-qPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and K-Ras in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.

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Acknowledgements

We would like to acknowledge the helpful comments on this paper received from our reviewers.

Author Contributions

Mei Jin, Zi-Wen Long, Jing Yang and Xiang Lin designed the study, collated the data, designed and developedthe database, carried out data analyses and produced the initial draft of the manuscript. Mei Jin andZi-Wen Long contributed to revise the manuscript. All authors have read and approved the final submitted manuscript.

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Authors and Affiliations

  1. Department of Surgery, Shigatse People’s Hospital, Shigatse, Tibet, 85700, People’s Republic of China

    Mei Jin, Jing Yang & Xiang Lin

  2. Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China

    Zi-Wen Long

  3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China

    Zi-Wen Long

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  1. Mei Jin
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Correspondence to Zi-Wen Long.

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Jin, M., Long, ZW., Yang, J. et al. Correlations of IGF-1R and COX-2 Expressions with Ras and BRAF Genetic Mutations, Clinicopathological Features and Prognosis of Colorectal Cancer Patients. Pathol. Oncol. Res. 24, 45–57 (2018). https://doi.org/10.1007/s12253-017-0195-5

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  • DOI: https://doi.org/10.1007/s12253-017-0195-5

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