MUC4 isoforms expression profiling and prognosis value in Chinese melanoma patients

Mucin 4 (MUC4), a type I membrane-bound mucin, blocks apoptosis, promotes invasion, proliferation and migration and causes chemo-resistance in epithelial cancers. However, the expression profiling and clinical implications of MUC4 alternative splicing during cancer pathogenesis, including melanoma,...

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Published in:	Clinical and experimental medicine 2020-05, Vol.20 (2), p.299-311
Main Authors:	Yu, Jinyu, Xu, Longwen, Yan, Junya, Yu, Jiayi, Wu, Xiaowen, Dai, Jie, Guo, Jun, Kong, Yan
Format:	Article
Language:	eng
Subjects:	Adult Aged Aged, 80 and over Alternative splicing Apoptosis Asian Continental Ancestry Group Biomarkers, Tumor - genetics Cancer Cell Line, Tumor Chemotherapy Female Gene expression Gene Expression Regulation, Neoplastic Hematology Humans Internal Medicine Isoforms Male Medical prognosis Medicine Medicine & Public Health Melanoma Melanoma - drug therapy Melanoma - genetics Melanoma - mortality Melanoma - pathology Middle Aged Mucin Mucin-4 - genetics Multivariate analysis Oncology Original Article Prognosis Protein Isoforms - genetics Skin Neoplasms - drug therapy Skin Neoplasms - genetics Skin Neoplasms - mortality Skin Neoplasms - pathology Tumor cell lines Young Adult
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Summary:	Mucin 4 (MUC4), a type I membrane-bound mucin, blocks apoptosis, promotes invasion, proliferation and migration and causes chemo-resistance in epithelial cancers. However, the expression profiling and clinical implications of MUC4 alternative splicing during cancer pathogenesis, including melanoma, remain obscure. We examined the mRNA expression profiling of MUC4 isoforms in gastrointestinal cancer cell lines, melanoma cell lines, human epidermal melanocyte cells, as well as 138 cases of human melanoma tissues by RT-qPCR. Then we analyzed the relationship of mRNA expression of MUC4 isoforms to clinicopathological characteristics and survival of patients. The dynamic mRNA expression profiling of MUC4 isoforms was found in melanoma. We identified MUC4 isoform f was highly expressed in melanoma cell lines but negative in gastrointestinal cancer cell lines. Clinical analysis based on 138 cases of human melanomas showed that MUC4 isoform d was related with melanoma subtypes ( p = 0.028) and TNM stage ( p = 0.036). MUC4 isoform e was related with tumor thickness ( p = 0.004) and T stage ( p = 0.036). The Kaplan–Meier assay showed that the median overall survival (OS) for patients with MUC4 isoform f high expression was significantly shorter than that of patients with low expression ( p = 0.024). And the median PFS of the patients with high expression of MUC4 isoform d or e was significantly shorter than that of with low expression ( p = 0.012 and 0.035, respectively). Multivariate analysis indicated that high level of MUC4 isoform f was an independent prognostic factor for OS, and MUC4 isoform d was an independent prognostic factor for PFS of patients treated with chemotherapy. In conclusion, our results indicate that the dynamic MUC4 isoforms expressed in melanoma, and MUC4 isoform d and f might be served as a novel prognostic indicator of melanoma patients.
ISSN:	1591-8890 1591-9528