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Supplementary Material for: Host MICA Polymorphism as a Potential Predictive Marker in Response to Chemotherapy for Colorectal Liver Metastases

posted on 03.07.2018, 08:13 by Nishioka Y., Shindoh J., Inagaki Y., Gonoi W., Mitsui J., Abe H., Yoshioka R., Yoshida S., Fukayama M., Tsuji S., Hashimoto M., Hasegawa K., Kokudo N.
Background: Understanding the genetic background of a tumor is important to better stratify patient prognosis and select optimal treatment. For colorectal liver metastases (CLM), however, clinically available biomarkers remain limited. Methods: After a comprehensive sequencing of 578 cancer-related genes in 10 patients exhibiting very good/poor responses to chemotherapy, the A5.1 variant of the MICA gene was selected as a potential biomarker for CLM. The clinical relevance of MICA A5.1 was then investigated in 58 patients who underwent CLM resection after chemotherapy. Results: The A5.1 variant was observed in 16 (27.6%) patients examined using direct DNA sequencing, and a very high concordance rate (56/58, 96.6%) for the MICA variant was confirmed between tumor tissues and normal liver parenchyma. A multivariate analysis of 38 patients with no history of treatment with anti-EGFR antibodies confirmed that MICA A5.1 was significantly correlated with an optimal CT morphologic response (OR 11.67; 95% CI 2.08–65.60; p = 0.005) and tended to be correlated with a tumor viability of < 20% after chemotherapy (OR 5.91; 95% CI 0.97–36.02; p = 0.054). MICA A5.1 was also associated with a decreased risk of progression after CLM resection. Conclusion: The MICA A5.1 polymorphism was associated with a better CT morphologic response to chemotherapy and a reduced risk of relapse after CLM resection. Given the high concordance rate in MICA variants between normal liver tissue and CLM, the genetic background of the host could be a new biomarker for CLM.