Differentially expressed full-length, fusion and novel isoforms transcripts-based signature of well-differentiated keratinized oral squamous cell carcinoma
| Autor: | Satya Prakash Agarwal, Anil Kumar, Abhishek Mishra, Ratnesh Kumar Tripathi, Madan Lal Brahma Bhatt, Archana Mishra, Mayank Jain, Rebecca Chowdhry, Nawazish Alam, Dinesh Kumar Sahu, Hari Shyam, Divya Mehrotra, Anjana Singh, Sameer Gupta, Ravi Kant, Arun Chaturvedi, Neetu Singh, Madhu Mati Goel, Preeti Agarwal, Pratap Shankar, Devendra K Gupta, Manish Bajpai |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene isoform Microarray Cell growth Hemidesmosome In silico integrative bioinformatics Biology Phenotype differentially expressed gene Transcriptome transcriptomics stomatognathic diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine oral tongue squamous cell carcinoma Oncology Fusion transcript 030220 oncology & carcinogenesis Cancer research microarray Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Highly keratinized oral squamous cell carcinoma (OSCC) exhibits an improved response to treatment and prognosis compared with weakly keratinized OSCC. Therefore, we aimed to develop gene transcript signature and to identify novel full-length isoforms, fusion transcript and non-coding RNA to differentiate well-differentiated (WD) with Moderately Differentiated (MD)/Poorly Differentiated (PD)/WD-lymphadenopathy OSCC through, HTA, Isoform sequencing, and NanoString. Additionally, specific copy number gain and loss were also identify in WD keratinized OSCC through Oncoscan array and validated through Real-time PCR in histopathologically characterized FFPE-WD keratinized OSCC. Three-hundred-thirty-eight (338) differentially expressed full-length (FL) transcript isoforms (317 upregulated and 21 down-regulated in OSCC) were identified through Isoform Sequencing using the PacBio platform. Thirty-four (34) highly upregulated differentially expressed transcripts from IsoSeq data were also correlated with HTA2.0 and validated in 42 OSCC samples. We were able to identify 18 differentially expressed transcripts, 12 fusion transcripts, and two long noncoding RNAs. These transcripts were involved in increased cell proliferation, dysregulated metabolic reprogramming, oxidative stress, and immune system markers with enhanced immune rearrangements, suggesting a cancerous nature. However, an increase in proteasomal activity and hemidesmosome proteins suggested an improved prognosis and tumor cell stability in keratinized OSCC and helped to characterize WD with MD/PD/WD with lymphadenopathy OSCC. Additionally, novel isoforms of IL37, NAA10, UCHL3, SPAG7, and RAB24 were identified while in silico functionally validated SPAG7 represented the premalignant phenotype of keratinized (K4) OSCC. Most importantly we found copy number gain and overexpression of EGFR suggest that TKIs may also be used as therapeutics in WD-OSCCs. |
| Databáze: | OpenAIRE |
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