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Clinical Research
Investigation of the prognostic value of immune microenvironment typing in malignant melanoma based on gene expression profile
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Abstract:
Objective: To investigate the prognostic value of microenvironmental typing in patients with malignant melanoma (MM). Methods: Next generation sequencing (NGS) was performed on 87 cases of primary MM tissues that had been surgically removed in Nanjing Drum Tower Hospital from July 2010 to May 2017. Immunohistochemistry was carried out to detect the expressions of PD-1, PD-L1, CD3+TIL, MSH2, MSH6, PMS2 and MLH1. The survival of these patients was followed up. Then, the effects of different immune microenvironment types on prognosis and gene expression profile of patients were analyzed. Results: According to the expression level of PD-L1 and TIL, MM patients were divided into 4 immune microenvironment subtypes, including PD-L1+TIL+ group (15/87, 17.24%), PD-L1+ TIL- group (15/87, 17.24%), PD-L1- TIL+ group (20/87, 22.99%), and PD-L1- TIL- group (37/87, 42.53%). The median disease free survival (DFS) time of PD-L1+ TIL+ patients was significantly longer than that of PD-L1- TIL- patients (P<0.05)， which might be related with more copy number amplification of poor prognosis-associated genes in PD-L1- TIL- patients, such as CDK4, MCL1, MYC, AKT2, CCND1 and FGF19. It was found that the expression of PD-1 in PD-L1+ TIL+ patients was significantly higher than that in PD-L1- TIL- ones (P<0.01)，which may be related to the co-expression or un-expression of PD-L1 and PD-1 as well as TIL and PD-1. Conclusion: The microenvironment of MM patients can be divided into four subtypes according to the expression of PD-L1 and TIL, which can distinguish the prognosis of MM patients. The PD-L1- TIL- patients have more copy number amplification of poor prognosis related genes.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81872484, No. 82073365), and the Social Development Project of Jiangsu Province (No. BE2019605)
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