Cell division cycle-associated protein 1 as a new melanoma-associated antigen

J Dermatol. 2016 Dec;43(12):1399-1405. doi: 10.1111/1346-8138.13436. Epub 2016 May 30.

Abstract

Immune checkpoint inhibitors have increased the median survival of melanoma patients. To improve their effects, antigen-specific therapies utilizing melanoma-associated antigens should be developed. Cell division cycle-associated protein 1 (CDCA1), which has a specific function at the kinetochores for stabilizing microtubule attachment, is overexpressed in various cancers. CDCA1, which is a member of cancer-testis antigens, does not show detectable expression levels in normal tissues. Quantitative reverse transcription polymerase chain reaction and immunoblotting analyses revealed that CDCA1 was expressed in all of the tested melanoma cell lines, 74% of primary melanomas, 64% of metastatic melanomas and 25% of nevi. An immunohistochemical analysis and a Cox proportional hazards model showed that CDCA1 could be a prognostic marker in malignant melanoma (MM) patients. CDCA1-specific siRNA inhibited the cell proliferation of SKMEL2 and WM115 cells, but did not reduce the migration or invasion activity. These results suggest that CDCA1 may be a new therapeutic target of melanoma.

Keywords: NDC80 kinetochore complex component; cancer-testis antigen; cell division cycle-associated protein 1; immunotherapy; melanoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunohistochemistry
  • Kinetochores / metabolism
  • Lymphatic Metastasis
  • Male
  • Melanoma / immunology*
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Nevus / immunology*
  • Nevus / mortality
  • Nevus / pathology
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / pathology
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Rate
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • NUF2 protein, human
  • RNA, Small Interfering