4.4 Article

PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM)

Journal

JOURNAL OF IMMUNOTHERAPY
Volume 44, Issue 6, Pages 214-223

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0000000000000374

Keywords

PMEL; immune infiltration; prognosis; SKCM

Funding

  1. CAMS Innovation Fund for Medical Sciences (CIFMS) [2017-I2M-1-005]
  2. Capital characterized clinical application research Fund of Beijing Municipal Science and Technology Commission of China [Z171100001017210]
  3. Beijing Hope Run Special Fund of Cancer Foundation of China [LC2016L01]
  4. Special Fund for Clinical Research of Wu Jieping Medical Foundation [320.6750.14298]
  5. Chinese Academy of Medical Sciences Innovative Medicine [2016-I2M-1-007]

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This study found that Premelanosome protein (PMEL) plays a crucial role in the formation of melanosomal fibrils and has an impact on the treatment of melanoma. In skin cutaneous melanoma, high levels of PMEL expression were associated with poor overall survival and negatively correlated with infiltration of certain immune cells. Further research is needed to explore the potential of PMEL as a negative prognostic marker or new immunotherapy target in melanoma.
Premelanosome protein (PMEL) is crucial for the formation of melanosomal fibrils through the transition from stage I to stage II melanosomes. It was used as a target antigen in some adoptive T-cell therapy of melanoma. The correlation of PMEL to prognosis and immune cell infiltration level are unknown in melanoma. The PMEL expression was evaluated via Tumor Immune Estimation Resource, Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). We also evaluate the influence of PMEL on overall survival via GEPIA, PrognoScan, and immunohistochemistry in human tissue microarray. The correlation between PMEL expression level and immune cell or gene markers of immune infiltration level was explored on Tumor Immune Estimation Resource and GEPIA. PMEL expression was significantly higher in skin cutaneous melanoma (SKCM) and SKCM-metastasis in comparison with the other cancers. In SKCM, PMEL expression in high levels was associated with poor overall survival. In both SKCM and SKCM-metastasis patients, PMEL expression is negatively correlated with the infiltration cells of CD8(+) T cells, macrophages, and neutrophils. Programmed cell-death protein 1 just showed response rates ranging from 20% to 40% in patients with melanoma, so it is critical to discover a new therapeutic target. PMEL is negatively associated with immune cell infiltration and can be as a negative prognosis marker or new immunotherapy target in SKCM and SKCM-metastasis.

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