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Zhou S, Han Y, Li J, et al. New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma . Front Oncol. 2021;11:745384doi: 10.3389/fonc.2021.745384.
Zhou, S., Han, Y., Li, J., Pi, X., Lyu, J., Xiang, S., Zhou, X., Chen, X., Wang, Z., & Yang, R. (2021). New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma . Frontiers in oncology, 11745384. https://doi.org/10.3389/fonc.2021.745384
Zhou, Sitong, et al. "New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma ." Frontiers in oncology vol. 11 (2021): 745384. doi: https://doi.org/10.3389/fonc.2021.745384
Zhou S, Han Y, Li J, Pi X, Lyu J, Xiang S, Zhou X, Chen X, Wang Z, Yang R. New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma . Front Oncol. 2021 Oct 13;11:745384. doi: 10.3389/fonc.2021.745384. eCollection 2021. PMID: 34722301; PMCID: PMC8548670.
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Front Oncol. 2021 Oct 13;11:745384. doi: 10.3389/fonc.2021.745384. eCollection 2021.

New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma .

Frontiers in oncology

Sitong Zhou, Yuanyuan Han, Jiehua Li, Xiaobing Pi, Jin Lyu, Shijian Xiang, Xinzhu Zhou, Xiaodong Chen, Zhengguang Wang, Ronghua Yang

Affiliations

  1. Department of Dermatology, The First People's Hospital of Foshan, Foshan, China.
  2. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, China.
  3. Department of Pathology, The First People's Hospital of Foshan, Foshan, China.
  4. Department of Pharmacy, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
  5. The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
  6. Department of Burn Surgery and Skin Regeneration, The First People's Hospital of Foshan, Foshan, China.
  7. Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, China.

PMID: 34722301 PMCID: PMC8548670 DOI: 10.3389/fonc.2021.745384

Abstract

Skin cutaneous melanoma (SKCM) is the most aggressive and fatal type of skin cancer. Its highly heterogeneous features make personalized treatments difficult, so there is an urgent need to identify markers for early diagnosis and therapy. Detailed profiles are useful for assessing malignancy potential and treatment in various cancers. In this study, we constructed a co-expression module using expression data for cutaneous melanoma. A weighted gene co-expression network analysis was used to discover a co-expression gene module for the pathogenesis of this disease, followed by a comprehensive bioinformatics analysis of selected hub genes. A connectivity map (CMap) was used to predict drugs for the treatment of SKCM based on hub genes, and immunohistochemical (IHC) staining was performed to validate the protein levels. After discovering a co-expression gene module for the pathogenesis of this disease, we combined GWAS validation and DEG analysis to identify 10 hub genes in the most relevant module. Survival curves indicated that eight hub genes were significantly and negatively associated with overall survival. A total of eight hub genes were positively correlated with SKCM tumor purity, and 10 hub genes were negatively correlated with the infiltration level of CD4+ T cells and B cells. Methylation levels of seven hub genes in stage 2 SKCM were significantly lower than those in stage 3. We also analyzed the isomer expression levels of 10 hub genes to explore the therapeutic target value of 10 hub genes in terms of alternative splicing (AS). All 10 hub genes had mutations in skin tissue. Furthermore, CMap analysis identified cefamandole, ursolic acid, podophyllotoxin, and Gly-His-Lys as four targeted therapy drugs that may be effective treatments for SKCM. Finally, IHC staining results showed that all 10 molecules were highly expressed in melanoma specimens compared to normal samples. These findings provide new insights into SKCM pathogenesis based on multi-omics profiles of key prognostic biomarkers and drug targets. GPR143 and SLC45A2 may serve as drug targets for immunotherapy and prognostic biomarkers for SKCM. This study identified four drugs with significant potential in treating SKCM patients.

Copyright © 2021 Zhou, Han, Li, Pi, Lyu, Xiang, Zhou, Chen, Wang and Yang.

Keywords: WGCNA; bioinformatic analysis; biomarker; cutaneous melanoma; experimental validation

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Cell Mol Life Sci. 2015 Apr;72(7):1249-60 - PubMed
  2. Cancers (Basel). 2021 Jan 09;13(2): - PubMed
  3. Genomics. 2020 Sep;112(5):3696-3702 - PubMed
  4. Elife. 2019 Jun 06;8: - PubMed
  5. Neoplasia. 2017 Aug;19(8):649-658 - PubMed
  6. Pigment Cell Melanoma Res. 2010 Apr;23(2):160-70 - PubMed
  7. Cancer Cell Int. 2020 May 25;20:195 - PubMed
  8. Nat Commun. 2019 Apr 3;10(1):1523 - PubMed
  9. Nat Immunol. 2013 Oct;14(10):1014-22 - PubMed
  10. Pigment Cell Melanoma Res. 2017 Sep;30(5):454-466 - PubMed
  11. Nucleic Acids Res. 2018 Jan 4;46(D1):D246-D251 - PubMed
  12. Cancer Res. 2017 Nov 1;77(21):e108-e110 - PubMed
  13. Nucleic Acids Res. 2003 Jan 1;31(1):258-61 - PubMed
  14. Front Oncol. 2020 Sep 09;10:1710 - PubMed
  15. Carcinogenesis. 2018 Jul 30;39(8):1016-1025 - PubMed
  16. Molecules. 2020 Jul 26;25(15): - PubMed
  17. Front Oncol. 2019 Aug 27;9:812 - PubMed
  18. Front Oncol. 2020 Oct 16;10:581985 - PubMed
  19. Nucleic Acids Res. 2015 Apr 20;43(7):e47 - PubMed
  20. Cell Prolif. 2020 Mar;53(3):e12770 - PubMed
  21. Anticancer Res. 2000 Nov-Dec;20(6D):5041-4 - PubMed
  22. Br J Cancer. 2014 May 13;110(10):2489-95 - PubMed
  23. Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560 - PubMed
  24. Br J Dermatol. 2019 Dec;181(6):1146-1155 - PubMed
  25. Cancer Cell Int. 2021 Feb 4;21(1):88 - PubMed
  26. Genome Res. 2003 Nov;13(11):2498-504 - PubMed
  27. IUBMB Life. 2020 Jul;72(7):1364-1378 - PubMed
  28. J Invest Dermatol. 2014 Aug;134(8):2202-2211 - PubMed
  29. Aging (Albany NY). 2020 Oct 26;12(20):20684-20701 - PubMed
  30. J Clin Med. 2020 Feb 03;9(2): - PubMed
  31. Am J Pathol. 2003 Jul;163(1):333-43 - PubMed
  32. J Cell Physiol. 2019 Apr;234(4):3307-3320 - PubMed
  33. Mol Biol Cell. 2020 Nov 15;31(24):2687-2702 - PubMed
  34. Int J Oncol. 2020 Sep;57(3):619-630 - PubMed
  35. BMC Bioinformatics. 2008 Dec 29;9:559 - PubMed
  36. Aging (Albany NY). 2019 Jul 18;11(14):5081-5107 - PubMed
  37. Front Immunol. 2020 Sep 10;11:2105 - PubMed
  38. Front Oncol. 2020 Nov 10;10:570654 - PubMed
  39. Cancer Res. 2006 Nov 15;66(22):10639-42 - PubMed
  40. PLoS Biol. 2019 Nov 25;17(11):e3000434 - PubMed
  41. Nat Commun. 2020 Jun 5;11(1):2858 - PubMed

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