MGMT in colorectal cancer: a promising component of personalized treatment.

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.

• Authors: Le Zhang, Jing Zeng, Zhaolei Zeng, Fenghua Wang, Deshen Wang, Cui Chen, Cong Li, Xin An, Ruihua Xu, Peng Huang, Yi Ba, Yuhong Li
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 8 Pg. 11443-56 (Aug 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 27006309 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Tumor Suppressor Proteins
• Dacarbazine
• DNA Modification Methylases
• MGMT protein, human
• DNA Repair Enzymes
• Temozolomide

Topics

• Adenocarcinoma (drug therapy, genetics, mortality)
• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Blotting, Western
• Cell Line, Tumor
• Colorectal Neoplasms (drug therapy, genetics, mortality)
• DNA Modification Methylases (genetics)
• DNA Repair Enzymes (genetics)
• Dacarbazine (analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Drug Resistance, Neoplasm (genetics)
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Precision Medicine
• Prognosis
• Proportional Hazards Models
• Temozolomide
• Tumor Suppressor Proteins (genetics)