DNA repair pathway activation features in follicular and papillary thyroid tumors, interrogated using 95 experimental RNA sequencing profiles

DNA repair can prevent mutations and cancer development, but it can also restore damaged tumor cells after chemo and radiation therapy. We performed RNA sequencing on 95 human pathological thyroid biosamples including 17 follicular adenomas, 23 follicular cancers, 3 medullar cancers, 51 papillary ca...

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Published in:	Heliyon 2021-03, Vol.7 (3), p.e06408-e06408, Article e06408
Main Authors:	Vladimirova, Uliana, Rumiantsev, Pavel, Zolotovskaia, Marianna, Albert, Eugene, Abrosimov, Aleksander, Slashchuk, Konstantin, Nikiforovich, Petr, Chukhacheva, Olga, Gaifullin, Nurshat, Suntsova, Maria, Zakharova, Galina, Glusker, Alexander, Nikitin, Daniil, Garazha, Andrew, Li, Xinmin, Kamashev, Dmitriy, Drobyshev, Alexei, Kochergina-Nikitskaya, Irina, Sorokin, Maxim, Buzdin, Anton
Format:	Article
Language:	eng
Subjects:	DNA repair Follicular thyroid adenoma Molecular biomarkers Molecular pathway analysis Papillary thyroid cancer Personalized medicine Radiation iodine therapy resistance RNA sequencing Systems biology Thyroid cancer
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Summary:	DNA repair can prevent mutations and cancer development, but it can also restore damaged tumor cells after chemo and radiation therapy. We performed RNA sequencing on 95 human pathological thyroid biosamples including 17 follicular adenomas, 23 follicular cancers, 3 medullar cancers, 51 papillary cancers and 1 poorly differentiated cancer. The gene expression profiles are annotated here with the clinical and histological diagnoses and, for papillary cancers, with BRAF gene V600E mutation status. DNA repair molecular pathway analysis showed strongly upregulated pathway activation levels for most of the differential pathways in the papillary cancer and moderately upregulated pattern in the follicular cancer, when compared to the follicular adenomas. This was observed for the BRCA1, ATM, p53, excision repair, and mismatch repair pathways. This finding was validated using independent thyroid tumor expression dataset PRJEB11591. We also analyzed gene expression patterns linked with the radioiodine resistant thyroid tumors (n = 13) and identified 871 differential genes that according to Gene Ontology analysis formed two functional groups: (i) response to topologically incorrect protein and (ii) aldo-keto reductase (NADP) activity. We also found RNA sequencing reads for two hybrid transcripts: one in-frame fusion for well-known NCOA4-RET translocation, and another frameshift fusion of ALK oncogene with a new partner ARHGAP12. The latter could probably support increased expression of truncated ALK downstream from 4th exon out of 28. Both fusions were found in papillary thyroid cancers of follicular histologic subtype with node metastases, one of them (NCOA4-RET) for the radioactive iodine resistant tumor. The differences in DNA repair activation patterns may help to improve therapy of different thyroid cancer types under investigation and the data communicated may serve for finding additional markers of radioiodine resistance. DNA repair, follicular thyroid adenoma, RNA sequencing, thyroid cancer, personalized medicine, molecular biomarkers, molecular pathway analysis, radiation iodine therapy resistance, papillary thyroid cancer, systems biology.
ISSN:	2405-8440 2405-8440