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MGMT in colorectal cancer: a promising component of personalized treatment

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Tumor Biology

Abstract

The identification of new, effective drugs is a pressing need in colorectal cancer (CRC) rescue therapy. Data examining O 6-methylguanine-DNA-methyl transferase (MGMT) and its predictive role in temozolomide (TMZ) treatment in CRC are scarce. In this study, the effect of MGMT status on the cytotoxic sensitivity caused by TMZ was analyzed using cytology proliferation assays in colon cancer cell lines. MGMT protein expression was assessed with immunohistochemistry in 385 patients. Concordance between primary and metastatic sites and the role of MGMT status on survival were statistically analyzed. TMZ sensitivity was significantly affected by the level of MGMT protein expression. Of 385 cases, 13 (3.4 %) demonstrated loss of MGMT expression. However, low MGMT expression levels were significantly more common in signet ring cell carcinomas (p = 0.011). In 111 of 385 cases, the overall concordance of MGMT status between primary tumor and metastatic sites was 66.67 % (κ = 0.271, p < 0.001). The median progression-free survival was significantly different between groups with low or high MGMT expression for the irinotecan-based regimen (p = 0.025), but MGMT protein expression was not observed to be a prognostic factor. In conclusion, MGMT was an important in vitro predictor of TMZ activity in CRC. The rate of MGMT protein loss was low in metastatic CRC patients from China, and MGMT might be more commonly lost in signet ring cell carcinoma. The MGMT status at primary and metastatic sites was consistent, but the power of concordance was poor. Further study into these topics is warranted.

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Author notes

    Authors and Affiliations

    1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651# Dongfeng Road East, Guangzhou, 510060, China

      Le Zhang, Jing Zeng, Zhaolei Zeng, Fenghua Wang, Deshen Wang, Cui Chen, Cong Li, Xin An, Ruihua Xu, Peng Huang & Yuhong Li

    2. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

      Le Zhang, Fenghua Wang, Deshen Wang, Cui Chen, Cong Li, Xin An, Ruihua Xu & Yuhong Li

    3. Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

      Le Zhang & Yi Ba

    4. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China

      Jing Zeng

    5. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China

      Zhaolei Zeng & Peng Huang

    6. Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

      Peng Huang

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    1. Le Zhang
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    Correspondence to Yuhong Li.

    Ethics declarations

    All of the procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments. Informed consent was obtained from each participant included in the study.

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    Additional information

    Le Zhang and Jing Zeng contributed equally to this work.

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    Zhang, L., Zeng, J., Zeng, Z. et al. MGMT in colorectal cancer: a promising component of personalized treatment. Tumor Biol. 37, 11443–11456 (2016). https://doi.org/10.1007/s13277-016-5014-1

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    • DOI: https://doi.org/10.1007/s13277-016-5014-1

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