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Mutations of EGFR or KRAS and expression of chemotherapy-related genes based on small biopsy samples in stage IIIB and IV inoperable non-small cell lung cancer

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purposes

Epidermal growth factor receptor (EGFR) and KRAS mutations may predict the outcome of targeted drug therapy and also may be associated with the efficacy of chemotherapy in patients with non-small cell lung cancer (NSCLC). This report investigated the relation of EGFR or KRAS mutation and expression of chemotherapy-related genes, including excision repair cross-complementing 1 (ERCC1), thymidylate synthetase (TYMS), ribonucleotide reductase subunit M1 (RRM1) and class III β-tubulin (TUBB3), as a potential explanation for these observations.

Methods

A total of 143 patients with stage IIIB and IV NSCLC from bronchoscopy or percutaneous lung biopsy obtained tumor samples were analyzed concurrently for EGFR or KRAS mutations, and mRNA expression of ERCC1, TYMS, RRM1 and TUBB3. EGFR or KRAS mutations were detected with xTAG liquidchip technology (xTAG-LCT), and mRNA expression levels of four genes were detected by branched DNA-liquidchip technology (bDNA-LCT).

Results

Of 143 patients, 63 tumors were positive for EGFR-activating mutations, and 16 tumors were positive for KRAS mutations. EGFR-activating mutations are more frequent in females, adenocarcinoma and non-smokers patients, and KRAS mutations are more frequent in smoking patients. ERCC1 mRNA levels were significantly associated with histological type and tumor differentiation, whereas TYMS levels were significantly associated with age. NSCLC specimens that harboring EGFR-activating mutations are more likely to express low ERCC1 and high TUBB3 mRNA levels, whereas tumors from patients with NSCLC harboring KRAS mutation are more likely to express high ERCC1 mRNA levels.

Conclusions

Mutations and expression of chemotherapy-related genes may provide a basis for the selection of suitable molecular markers for individual treatment in a population with stage IIIB and IV NSCLC.

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Acknowledgments

This study was sponsored by a research Grant from the PhD Research Fund (No. BS2012-16) provided by the Second Affiliated Hospital of Harbin Medical University. Our thanks to all participants who consented to take part in this trial.

Conflict of interest

None declared.

Ethical standards

This human study has been approved by the Ethical Review Committee of Second Affiliated Hospital of Harbin Medical University and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants had signed informed consent.

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Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People’s Republic of China

    Li-Li Deng, Yang Guo & Di Wang

  2. Dental Hospital, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Nangang District, Harbin, 150001, Heilongjiang, People’s Republic of China

    Hong-Bin Deng & Xing Lv

  3. Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Rd, Harbin, 150081, Heilongjiang, People’s Republic of China

    Chang-Lian Lu

  4. Department of Respiratory Medicine, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People’s Republic of China

    Chun-Hua Yan & Yu-Xia Shao

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  1. Li-Li Deng
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  2. Hong-Bin Deng
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  3. Chang-Lian Lu
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  5. Di Wang
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Correspondence to Yu-Xia Shao.

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Li-Li Deng and Hong-Bin Deng have contributed equally to this work.

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Deng, LL., Deng, HB., Lu, CL. et al. Mutations of EGFR or KRAS and expression of chemotherapy-related genes based on small biopsy samples in stage IIIB and IV inoperable non-small cell lung cancer. J Cancer Res Clin Oncol 140, 2097–2105 (2014). https://doi.org/10.1007/s00432-014-1751-y

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  • DOI: https://doi.org/10.1007/s00432-014-1751-y

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