An androgen receptor-based signature to predict prognosis and identification of ORC1 as a therapeutical target for prostate adenocarcinoma

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Bioinformatics and Genomics

Main article text

 

Introduction

Methods and materials

Acquisition of cell samples and PRAD population cohorts

Processing of single-cell RNA-seq data

Identification of ARGs model in PRAD population cohorts

Profiles of tumor mutation burden and correlation analysis

Consensus clustering

Functional analysis

Cell lines and cell culture

Plasmid construction, transfection, and establishment of stable cell lines

Cell counting kit-8 and 3D soft agar assay

Sphere formation assay

Animal experiments

Statistical analysis

Results

Single-cell RNA-seq profiling and TCGA-PRAD cohort identify a panel of ARGs in PRAD

Establishment of ARGs model in TCGA-PRAD cohort

Risk assessment and predictive efficacy of ARGs in internal and external PRAD cohorts

Cluster stratification of PRAD samples based on the identified ARGs

Experimental validations highlight ORC1 as an essential hit among the ARGs

AR activates ORC1 transcription to drive tumor progression and Enza-R in PRAD cells

Discussion

Supplemental Information

Original figures.

DOI: 10.7717/peerj.16850/supp-1

ARRIVE 2.0 Checklist.

DOI: 10.7717/peerj.16850/supp-3

Differential landscape of somatic mutation burden between high and low ARGs score levels.

(A) The mutational landscape reflected that mutated events occurred more frequently in high ARGs-score samples than that in low group. Besides, the Chi-square test revealed that TP53, KMT2D, FOXA1 and PTEN especially harbored more mutants compared with that in group with low risk ARGs scores. (B) Scatter plot exhibiting the associations between ARGs scores and TMB levels. (C) Kaplan-Meier analysis indicating the differential PFS survival outcomes between TMB-high and TMB-low groups.

DOI: 10.7717/peerj.16850/supp-4

Additional Information and Declarations

Competing Interests

All authors declare that they have no competing interests.

Author Contributions

Linjin Li conceived and designed the experiments, performed the experiments, analyzed the data, authored or reviewed drafts of the article, and approved the final draft.

Dake Chen conceived and designed the experiments, prepared figures and/or tables, and approved the final draft.

Xiang Chen performed the experiments, authored or reviewed drafts of the article, and approved the final draft.

Jianlong Zhu analyzed the data, authored or reviewed drafts of the article, and approved the final draft.

Wenshuo Bao performed the experiments, prepared figures and/or tables, and approved the final draft.

Chengpeng Li performed the experiments, prepared figures and/or tables, and approved the final draft.

Feilong Miao performed the experiments, authored or reviewed drafts of the article, and approved the final draft.

Rui Feng conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft.

Animal Ethics

The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):

The Institutional Animal Experimental Ethics Committee of the Third Clinical Institute Affiliated to Wenzhou Medical University (Approval no. WMU2071357-AC-03).

Data Availability

The following information was supplied regarding data availability:

All original figures are available in the Supplemental Files.

GSE99795; GSE116918; GSE70769, MSKCC-PRAD cohort.

Funding

The project was supported by the Basic Research Programs of Science and Technology Department of Wenzhou (Y20210171) and the Wenzhou associated of the Integration of Traditional and Western Medicine, clinical research fund (2021004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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