The integration of single-cell sequencing, TCGA, and GEO data analysis revealed that PRRT3-AS1 is a biomarker and therapeutic target of SKCM

Wancong Zhang; Xuqi Xie; Zijian Huang; Xiaoping Zhong; Yang Liu; Kit-Leong Cheong; Jianda Zhou; Shijie Tang

doi:10.3389/fimmu.2022.919145

The integration of single-cell sequencing, TCGA, and GEO data analysis revealed that PRRT3-AS1 is a biomarker and therapeutic target of SKCM

Front Immunol. 2022 Sep 23:13:919145. doi: 10.3389/fimmu.2022.919145. eCollection 2022.

Authors

Wancong Zhang^{1

2}, Xuqi Xie^{1

2}, Zijian Huang^{1

2}, Xiaoping Zhong^{1

2}, Yang Liu³, Kit-Leong Cheong³, Jianda Zhou⁴, Shijie Tang^{1

2}

Affiliations

¹ Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, China.
² Plastic Surgery Institute of Shantou University Medical College, Shantou, China.
³ Guangdong Provincial Key Laboratory of Marine Biotechnology, Department of Biology, College of Science, Shantou University, Shantou, China.
⁴ Department of Plastic and Reconstructive Surgery, Central South University Third Xiangya Hospital, Changsha, China.

Abstract

Introduction: Skin cutaneous melanoma (SKCM) is the world's fourth deadliest cancer, and advanced SKCM leads to a poor prognosis. Novel biomarkers for SKCM diagnosis and prognosis are urgently needed. Long non-coding RNAs (lncRNAs) provide various biological functions and have been proved to play a significant role in tumor progression. Single-cell RNA sequencing (scRNA-seq) enables genome analysis at the single-cell level. This study explored prognostic lncRNAs in SKCM based on scRNA-seq and bulk RNA sequencing data.

Materials and methods: The TCGA cohort and melanoma samples in the GEO database (GSE72056, GSE19234, GSE15605, GSE7553, and GSE81383) were included in this study. Marker genes were filtered, and ensemble lncRNAs were annotated. The clinical significance of selected lncRNAs was verified through TCGA and GEO dataset analysis. SiRNA transfection, wound-healing and transwell assays were performed to evaluate the effect of PRRT3-AS1 on cellular function. Immune infiltration of the selected lncRNAs was also exhibited.

Results: A 5-marker-lncRNAs model of significant prognostic value was constructed based on GSE72056 and the TCGA cohort. PRRT3-AS1 combined with DANCR was then found to provide significant prognostic value in SKCM. PRRT3-AS1 was filtered for its higher expression in more advanced melanoma and significant prognosis value. Cellular function experiments in vitro revealed that PRRT3-AS1 may be required for cancer cell migration in SKCM. PRRT3-AS1 was found to be related to epithelial-mesenchymal transition (EMT) signaling pathways. DNA methylation of PRRT3-AS1 was negatively related to PRRT3-AS1 expression and showed significant prognosis value. In addition, PRRT3-AS1 may suppress immune infiltration and be involved in immunotherapy resistance.

Conclusion: PRRT3-AS1 may be a diagnostic and prognostic biomarker of SKCM.

Keywords: GEO; PRRT3-AS1; SKCM; TCGA; biomarker; lncRNAs; scRNA-seq.

MeSH terms

Biomarkers
Data Analysis
Gene Expression Regulation, Neoplastic
Humans
Melanoma* / genetics
Melanoma* / therapy
Melanoma, Cutaneous Malignant
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Small Interfering
Skin Neoplasms*

Substances

Biomarkers
RNA, Long Noncoding
RNA, Small Interfering