Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients

Abstract Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully expl...

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Autores principales:	Manish Pratap Singh, Sandhya Rai, Nand K. Singh, Sameer Srivastava
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1dcdd6915e1546bf97a347ffed008d1a
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spelling	oai:doaj.org-article:1dcdd6915e1546bf97a347ffed008d1a2021-12-02T15:57:03ZTranscriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients10.1038/s41598-021-91154-x2045-2322https://doaj.org/article/1dcdd6915e1546bf97a347ffed008d1a2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91154-xhttps://doaj.org/toc/2045-2322Abstract Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A, and IL1R1). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes CXCL3, IL1B, MET and TNS1 genes (p = 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of TNS1 and MET were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these TNS1 and MET are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.Manish Pratap SinghSandhya RaiNand K. SinghSameer SrivastavaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manish Pratap Singh Sandhya Rai Nand K. Singh Sameer Srivastava Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
description	Abstract Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A, and IL1R1). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes CXCL3, IL1B, MET and TNS1 genes (p = 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of TNS1 and MET were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these TNS1 and MET are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.
format	article
author	Manish Pratap Singh Sandhya Rai Nand K. Singh Sameer Srivastava
author_facet	Manish Pratap Singh Sandhya Rai Nand K. Singh Sameer Srivastava
author_sort	Manish Pratap Singh
title	Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
title_short	Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
title_full	Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
title_fullStr	Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
title_full_unstemmed	Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
title_sort	transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in indian crc patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1dcdd6915e1546bf97a347ffed008d1a
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Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients

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