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Computational Gene Expression and Network Analysis of Myc Reveal Insights into Its Diagnostic and Prognostic Role in Subtypes of Renal Cancer

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Abstract

In this study, we analysed the Myc expression in the pan-kidney cohort (KIPAN) and kidney renal clear cell carcinoma (KIRC) in human tumour tissues compared to normal tissues. Myc is overexpressed and associated with poor overall survival (OS) in the KIPAN and KIRC. It shows that Myc plays a crucial role in the growth and maintenance of these malignancies. Additionally, we explored coexpressed genes, gene-set enrichment analysis of coexpressed genes, proteins and regulatory partners directly linked with Myc in KIPAN and KIRC and their role in cancer-specific events. Pathway enrichment analysis concluded that Myc-related genes are involved in many cancer-related pathways. Furthermore, we studied that among KIPAN, mutant forms of tumour suppressor genes have a poor prognosis and are associated with higher Myc expression but not in KIRC. This paper also investigates the correlation between Myc expression and promoter methylation, tumour-infiltrating lymphocytes, and the interaction of Myc with drugs. Our study indicates that Myc can be used as a diagnostic and prognostic biomarker in patients with KIPAN and KIRC with diverse clinical and pathological characteristics.

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Data Availability

RNA sequencing data from the Cancer Genome Atlas (TCGA) was extracted from the Broad GDAC Firehose (http://gdac.broadinstitute.org/). Renal cancer datasets [KIPAN and KIRC] were used in the current study.

Abbreviations

RCC:

Renal cell carcinoma

KIPAN:

Pan-kidney cohort (KICH + KIRC + KIRP)

KICH and chrRCC:

Kidney chromophobe

KIRC and ccRCC:

Kidney renal clear cell carcinoma

KIRP and pRCC:

Kidney renal papillary cell carcinoma

OS:

Overall survival

TP53:

Tumour protein 53

VH:

Von Hippel-Lindau syndrome

SETD2:

SET domain containing 2, histone lysine methyltransferase

HIFs:

Hypoxia inducible factors

TCGA:

The Cancer Genome Atlas

TIMER:

Tumour immune estimation resource

CTD:

Comparative Taxicogenomics Database

RSEM:

RNA-seq by expectation maximization

SD:

Standard deviation

mRNA:

Messenger ribonucleic acid

DNA:

Deoxyribonucleic acid

GO:

Gene ontology

GSEA:

Gene set enrichment analysis

NES:

Normalised enrichment score

FDR:

False discovery rate

KEGG:

Key Kyoto Encyclopedia of Genes and Genomes

TF:

Transcription factor

miRNAs:

Micro ribonucleic acid

GRN:

Gene-regulatory network

TNF:

Tumour necrosis factor

NF-κB:

Nuclear factor kappa B

PPI:

Protein-protein interaction

TFRC:

Transferrin receptor

KDM6B:

Lysine demethylase 6B

TSG:

Tumour suppressor gene

TILs:

Tumour-infiltrating lymphocytes

TGF:

Transforming growth factor

TGFβ:

Transforming growth factor beta

ATF4:

Activating transcription factor 4

MBD2:

Methyl-CpG-binding domain protein 2

PHD:

Prolyl hydroxylase

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Acknowledgements

We thank Dr. Asim Bikas Das (associate professor; National Institute of Technology, Warangal, Telangana) for critically reading the manuscript and for his constructive comments. We acknowledge financial assistance from the National Institute of Technology, Warangal, for providing the computational facility and fellowship for Ph.D. students.

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Authors and Affiliations

  1. Department of Biotechnology, National Institute of Technology Warangal, Warangal, 506004, Telangana, India

    Jyotsna Priyam & Urmila Saxena

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Jyotsna Priyam collected and analysed the data with the help of Urmila Saxena. Urmila Saxena conceived and designed the study. Writing, reviewing, editing, and original draft preparation was done by Jyotsna Priyam and Urmila Saxena. Visualization, investigation, and supervision were done by Urmila Saxena.

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Correspondence to Urmila Saxena.

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Highlights

1. Myc expression was high in tumour samples in comparison to normal in KIPAN [kidney chromophobe (KICH) + kidney renal clear cell carcinoma (KIRC) + kidney renal papillary cell carcinoma (KIRP)] and KIRC (kidney renal clear cell carcinoma).

2. Higher expressions of Myc were associated with poor overall survival in renal cancers (KIPAN and KIRC).

3. Coexpressed genes and directly linked proteins, transcription factors, and miRNAs with Myc in KIPAN and KIRC are analysed.

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Priyam, J., Saxena, U. Computational Gene Expression and Network Analysis of Myc Reveal Insights into Its Diagnostic and Prognostic Role in Subtypes of Renal Cancer. Appl Biochem Biotechnol 195, 4251–4276 (2023). https://doi.org/10.1007/s12010-023-04357-5

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