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Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort
Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with genetics, genomics, and the environmental influence in the causality of PCa, not many studies employing the Next Generation Sequencing (NGS) approaches of PCa have been carried out....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204445/ https://www.ncbi.nlm.nih.gov/pubmed/37218885 http://dx.doi.org/10.3390/diseases11020072 |
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author | Shukla, Nidhi Kour, Bhumandeep Sharma, Devendra Vijayvargiya, Maneesh Sadasukhi, T. C. Medicherla, Krishna Mohan Malik, Babita Bissa, Bhawana Vuree, Sugunakar Lohiya, Nirmal Kumar Suravajhala, Prashanth |
author_facet | Shukla, Nidhi Kour, Bhumandeep Sharma, Devendra Vijayvargiya, Maneesh Sadasukhi, T. C. Medicherla, Krishna Mohan Malik, Babita Bissa, Bhawana Vuree, Sugunakar Lohiya, Nirmal Kumar Suravajhala, Prashanth |
author_sort | Shukla, Nidhi |
collection | PubMed |
description | Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with genetics, genomics, and the environmental influence in the causality of PCa, not many studies employing the Next Generation Sequencing (NGS) approaches of PCa have been carried out. In our previous study, we identified some causal genes and mutations specific to Indian PCa using Whole Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify differentially expressed genes (DEGs) including long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using the RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened six patients who underwent prostatectomy; we performed whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz., GeneMANIA, Stringdb, Cytoscape-Cytohubba, and cbioportal, to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa, such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, and HN1L, and some other important genes known to be involved in different cancer pathways, such as COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1, etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, ENSG00000287903, and ENST00000647843.1 that need to be characterized further. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which perhaps have not been reported. This has set a precedent for us to validate candidates further experimentally, and we firmly believe this will pave a way toward the discovery of biomarkers and the development of novel therapies. |
format | Online Article Text |
id | pubmed-10204445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102044452023-05-24 Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort Shukla, Nidhi Kour, Bhumandeep Sharma, Devendra Vijayvargiya, Maneesh Sadasukhi, T. C. Medicherla, Krishna Mohan Malik, Babita Bissa, Bhawana Vuree, Sugunakar Lohiya, Nirmal Kumar Suravajhala, Prashanth Diseases Article Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with genetics, genomics, and the environmental influence in the causality of PCa, not many studies employing the Next Generation Sequencing (NGS) approaches of PCa have been carried out. In our previous study, we identified some causal genes and mutations specific to Indian PCa using Whole Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify differentially expressed genes (DEGs) including long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using the RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened six patients who underwent prostatectomy; we performed whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz., GeneMANIA, Stringdb, Cytoscape-Cytohubba, and cbioportal, to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa, such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, and HN1L, and some other important genes known to be involved in different cancer pathways, such as COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1, etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, ENSG00000287903, and ENST00000647843.1 that need to be characterized further. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which perhaps have not been reported. This has set a precedent for us to validate candidates further experimentally, and we firmly believe this will pave a way toward the discovery of biomarkers and the development of novel therapies. MDPI 2023-05-11 /pmc/articles/PMC10204445/ /pubmed/37218885 http://dx.doi.org/10.3390/diseases11020072 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shukla, Nidhi Kour, Bhumandeep Sharma, Devendra Vijayvargiya, Maneesh Sadasukhi, T. C. Medicherla, Krishna Mohan Malik, Babita Bissa, Bhawana Vuree, Sugunakar Lohiya, Nirmal Kumar Suravajhala, Prashanth Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort |
title | Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort |
title_full | Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort |
title_fullStr | Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort |
title_full_unstemmed | Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort |
title_short | Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort |
title_sort | towards understanding the key signature pathways associated from differentially expressed gene analysis in an indian prostate cancer cohort |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204445/ https://www.ncbi.nlm.nih.gov/pubmed/37218885 http://dx.doi.org/10.3390/diseases11020072 |
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