Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets.

Yang-Yi Chen,Yi-Jen Chen,Wei-An Chang,En-Shyh Lin,Po-Lin Kuo

doi:10.3390/diagnostics9020059

Abstract

Major histocompatibility complex (MHC) class II molecules, encoded by human leukocyte antigen (HLA) class II genes, play important roles in antigen presentation and initiation of immune responses. However, the correlation between HLA class II gene expression level and patient survival and disease progression in cutaneous melanoma is still under investigation. In the present study, we analyzed microarray and RNA-Seq data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) using different bioinformatics tools. Survival analysis revealed higher expression level of HLA class II genes in cutaneous melanoma, especially HLA-DP and -DR, was significantly associated with better overall survival. Furthermore, the expressions of HLA class II genes were most closely associated with survival in cutaneous melanoma as compared with other cancer types. The expression of HLA class II co-expressed genes, which were found to associate with antigen processing, immune response, and inflammatory response, was also positively associated with overall survival in cutaneous melanoma. Therefore, the results indicated that increased HLA class II expression may contribute to enhanced anti-tumor immunity and related inflammatory response via presenting tumor antigens to the immune system. The expression pattern of HLA class II genes may serve as a prognostic biomarker and therapeutic targets in cutaneous melanoma.

Highlights

Cutaneous melanoma, a malignant tumor that originates from melanocytes, is an aggressive neoplasm with high metastatic potential that accounts for most of skin cancer related deaths
The expressions of most human leukocyte antigen (HLA) class II genes were significantly up-regulated in cutaneous melanoma, except HLA-DQB2, which was significantly down-regulated in cutaneous melanoma compared to normal skin tissues (Figure 1)
We investigated the changes in HLA class II mRNA expression based on cutaneous melanoma stages (Stage I, II, III, and IV according to American Joint Committee on Cancer (AJCC) TNM staging)

Summary

Introduction

A malignant tumor that originates from melanocytes, is an aggressive neoplasm with high metastatic potential that accounts for most of skin cancer related deaths. Reliable biomarkers for prediction of clinical outcome in patients with malignant melanoma are still under investigation. Diagnostics 2019, 9, 59 microenvironment during the early stage of tumor development may be important for predicting clinical outcome in patients with cutaneous melanoma. Human leukocyte antigen (HLA) class II antigen expression by tumor cells was reported to influence the tumor antigen-specific immune responses and prognosis in several cancer types [3], including melanoma [4]. Solid tumors originating from a variety of tissues were reported to express MHC-II molecules [5]. MHC-II molecules are critical for antigen presentation to CD4+ T-lymphocytes and its role in anti-tumor immunity is increasingly appreciated. Selected tumor-associated antigens (TAA) were effectively presented by MHC-II molecules to CD4+ T cells [6,7]

Methods

Results

Discussion

Conclusion