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Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments

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Abstract

Background

Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors.

Methods

We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM.

Results

We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis.

Conclusions

Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.

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Data Availability

TIMER (https://cistrome.shinyapps.io/timer/); CCLE (https://portals.broadinstitute.org/ccle); HPA (http://www.proteinatlas.org); CIBERSORT (http://cibersort.stanford.edu/); GEPIA (http://gepia.cancer-pku.cn/); Sangerbox (http://vip.sangerbox.com/home.html); UALCAN (http://ualcan.path.uab.edu); MethSurv (https://biit.cs.ut.ee/methsurv/); miRWalk (http://mirwalk.umm.uni-heidelberg.de/); miRDB (http://mirdb.org/); miRabel (http://bioinfo.univ-rouen.fr/mirabel/); CancerMIRNome (http://bioinfo.jialab-ucr.org/CancerMIRNome); Kaplan-Meier plotter (http://kmplot.com); STRING (http://string-db.org); GeneMANIA (http://www.genemania.org); cBioPortal (http://cbioportal.org); the UCSC Xena Browser (https://xena.ucsc.edu/); (CMap) (https://clue.io/).

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Acknowledgements

We would like to thank all the participants and research staff at the School of Pharmacy, Health Science Center, Xi’an Jiaotong University for their invaluable contributions to this work. A preprint has previously been published [62].

Funding

Our study was supported by the Natural Science Basic Research Plan in Shaan’xi Province of China (Grant no. 2019JQ-596), the Fundamental Research Funds for the Central Universities (xjj2018167 and xzy012020056), the Post-doctoral Sciences Foundation of Shaan’xi Province (Grant no. 2018BSHEDZZ91) and National Natural Science Foundation of China (81802788).

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Author notes

  1. Ruimin Bai, Pan Yin, Zixuan Xing and Shaobo Wu contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Ruimin Bai, Wen Zhang, Xinyu Ma, Xinyi Gan, Hao Lei & Yan Zheng

  2. Department of Medicine, Xi’an Jiaotong University, No. 76 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Pan Yin, Zixuan Xing, Shaobo Wu & Qijuan Zang

  3. Department of Imaging, the First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Yuxia Liang

  4. Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Yi Wei

  5. Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China

    Chaonan Zhang

  6. School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Bingling Dai

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  1. Ruimin Bai
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Contributions

R.B, P.Y, Z.X and S.W were major contributors in methodology, investigation, and writing. W.Z, X.M, X.G, Y.L, Q.Z, H.L, Y.W, and C.Z were responsible for the formal analysis and data curation. S.W, B.D, and Y.Z were responsible for the conceptualization and production of this study. All authors wrote the original draft and approved the final manuscript.

Corresponding authors

Correspondence to Shaobo Wu, Bingling Dai or Yan Zheng.

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10495_2023_1913_MOESM1_ESM.docx

Supplementary Material 1: See Tables S1-S4 and Fig. S1 in the Supplementary Material for comprehensive data analysis. Table S1 and Table S2 are supplements to Fig. 5. Table S3 and Table S4 are supplements to Fig. 7E-F

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Bai, R., Yin, P., Xing, Z. et al. Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments. Apoptosis 29, 372–392 (2024). https://doi.org/10.1007/s10495-023-01913-6

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