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

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...

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Bibliographic Details
Published in:Scientific reports 2021-06, Vol.11 (1), p.11765-11765, Article 11765
Main Authors: Singh, Manish Pratap, Rai, Sandhya, Singh, Nand K., Srivastava, Sameer
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
631/337
631/67
Adult
Age
Age of Onset
Aged
AKT protein
Bioinformatics
Biomarkers
c-Met protein
Cancer
CD22 antigen
Cell lineage
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Computational Biology - methods
CXCR2 protein
Cytokines
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Ontology
Humanities and Social Sciences
Humans
India
Interleukin 1
Male
MAP kinase
Middle Aged
Molecular Sequence Annotation
Mucosa
multidisciplinary
Protein Interaction Mapping - methods
Protein Interaction Maps
Rectum
Science
Science (multidisciplinary)
Signal Transduction
Transcriptome
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Summary: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 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-91154-x