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Study Identifies Potential Biomarker for Response to Immunotherapy for Melanoma

By: Joshua Swore
Posted: Monday, January 27, 2020

A study published in Clinical Epigenetics demonstrates a correlation between DNA methylation and mRNA expression of the genes TIM-3 and LGALS9 in melanoma. According to Tobias A.W. Holderried, MD, of Dana-Farber Cancer Institute, Boston, and international colleagues, their study seems to point “toward an epigenetic regulation of TIM-3 and LGALS9 via DNA methylation and might provide an avenue for the development of a predictive biomarker for response to immune checkpoint blockade.”

This study utilized data collected previously by the TCGA Research Network. It included the levels of mRNA expression and methylation of a total of 470 samples of skin cutaneous melanoma, which were used for the analysis. TCGA used Ilumina HiSeq 2000 RNA sequencing to assess mRNA expression levels and HumanMethylation 450 BeadChip to detect methylation levels.

Although many genes were analyzed for correlation between mRNA expression and methylation, the researchers identified the most significant correlations with TIM-3 (P < .05) and LGALS9 (P < .003). They also identified a positive correlation in the gene body region of TIM-3. Patients whose tumors had high expression of TIM-3 also had better overall survival (hazard ratio = 0.88, P = .007). There was a similar connection with LGALS9, with a positive correlation in the gene body and a higher expression of LGALS9 indicating a better overall survival (hazard ratio = 0.83, P = .001).

Finally, the authors found another correlation between mRNA expression of TIM-3 and LGALS9 in tumor-infiltrating leukocyte cells. “The better survival of patients with high TIM-3 and LGALS9 expression observed in our study might be due to a better immune response in the tumor, regardless of the high expression of TIM-3,” the investigators proposed.

Disclosure: For full disclosures of study authors, visit

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