Abstract
Lung cancer is one of the most commonly occurring malignant cancers with the highest rate of mortality globally. Difference between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) and their treatment strategies according to genetic markers may be helpful in reducing the cancer progression and increasing the overall survival (OS) in patients. LUSC is known for comparatively less typical onco-drivers, target therapy resistance, marked genomic complexity, and a reasonably higher mutation rate. The mRNA-seq data and clinical information of LUAD and LUSC cohorts from UCSC Xena comprising 437 and 379 patient samples were extracted. Differential expression and weighted network analyses revealed 47 and 18 hub differentially expressed genes (DEGs) corresponding to LUAD and LUSC cohorts. These hub DEGs were further subjected to protein–protein interaction network (PPIN) and OS analyses. Lower mRNA expression levels of both RPS15A and RPS7 worsened the OS of LUSC patients. Additionally, both these prognostic biomarkers were validated via external sources such as UALCAN, cBioPortal, TIMER, and HPA. RPS7 had higher mutation frequency compared to RPS15A and showed significant negative correlations with infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, and macrophages. Our findings provided novel insights into biomarker discovery and the critical role of ribosomal biogenesis especially smaller ribosomal subunit in pathogenesis of LUSC.
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Data availability
The raw HTSeq count datasets of TCGA-LUAD and LUSC used in our study were downloaded from UCSC Xena Browser available at https://xenabrowser.net/datapages/?dataset=TCGA-LUAD.htseq_counts.tsv&host=https%3A%2F%2Fgdc.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443 and https://xenabrowser.net/datapages/?dataset=TCGA-LUSC.htseq_counts.tsv&host=https%3A%2F%2Fgdc.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443.
Abbreviations
- TME :
-
Tumor microenvironment
- LC :
-
Lung cancer
- NSCLC :
-
Non-small cell lung cancer
- LUAD :
-
Lung adenocarcinoma
- SCLC :
-
Small cell lung cancer
- LUSC :
-
Lung squamous cell carcinoma
- OS :
-
Overall survival
- IHC :
-
Immunohistochemistry
- RP :
-
Ribosomal protein
- EMT :
-
Epithelial-mesenchymal transition
- DEGs :
-
Differentially expressed genes
- mRNA :
-
Messenger RNA
- DEA :
-
Differential expression analysis
- HTSeq :
-
High-throughput sequencing
- TNM :
-
Tumor node metastasis
- TCGA :
-
The Cancer Genome Atlas
- GDC :
-
Genomic Data Commons
- HGNC :
-
HUGO Gene Nomenclature Committee
- WGCN :
-
Weighted gene co-expression network
- WGCNA :
-
Weighted gene co-expression network analysis
- ME :
-
Module eigengene
- MEdiss :
-
MEdissimilarity
- k.in :
-
Intramodular connectivity
- MM :
-
Module membership
- PPIN :
-
Protein-protein interaction network
- TP53 :
-
Tumor protein P53
- HPA :
-
Human Protein Atlas
- SFT :
-
Scale-free topology
- MDS :
-
Multidimensional scaling
- TOM :
-
Topological overlap matrix
- RPS15A :
-
Ribosomal protein S15a
- RPS7 :
-
Ribosomal protein S7
- RFS :
-
Recurrence-free survival
- MDM2 :
-
Double minute 2 protein
- SMYD2 :
-
SET and MYND domain containing 2
- PIM1 :
-
Serine/threonine-protein kinase pim-1
- CDK2 :
-
Cyclin-dependent kinase 2
- CDK4 :
-
Cyclin-dependent kinase 4
- GLUT4 :
-
Glucose transporter type 4
- LDHB :
-
Lactate dehydrogenase B
- HIF-1α :
-
Hypoxia-inducible factor 1 subunit alpha
- mRNA :
-
Messenger RNA
- eIF4F :
-
Eukaryotic initiation factor 4F
- KM :
-
Kaplan–Meier
- CCNB1 :
-
Cyclin B1
- CCND1 :
-
Cyclin D1
- H3K36 :
-
H3 lysine 36
- H3K4 :
-
Histone H3 lysine K4
- BAX :
-
BCL2 associated X protein
- BAK1 :
-
BCL2 antagonist/killer 1
- BAD :
-
Bcl-2-like protein 8
- Bcl-2 :
-
BCL2 apoptosis regulator
- Bcl-xl :
-
Apoptosis regulator Bcl-X
- MdmX :
-
MDM4 regulator of P53
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Acknowledgements
The authors would like to thank Jamia Millia Islamia for providing infrastructure, journal access, and internet facilities. Prithvi Singh would like to thank the Indian Council of Medical Research (ICMR), Government of India for awarding him Senior Research Fellowship [Grant Number: BMI/11(89)/2020].
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Prithvi Singh: conceptualization; methodology; software; formal analysis; data curation; writing—original draft; writing—review and editing. Archana Sharma: writing—original draft; writing—review and editing. Bhupender Kumar: software; data curation; writing—review and editing. Anuradha Sinha: software; data curation; writing—review and editing. Mansoor Ali Syed: writing—review and editing. Ravins Dohare: writing—review and editing; supervision; project administration. All authors read and approved the final manuscript.
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Singh, P., Sharma, A., Kumar, B. et al. Integrative multiomics and weighted network approach reveals the prognostic role of RPS7 in lung squamous cell carcinoma pathogenesis. J Appl Genetics 64, 737–748 (2023). https://doi.org/10.1007/s13353-023-00782-8
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DOI: https://doi.org/10.1007/s13353-023-00782-8