Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MiRNome/small RNA analysis of thyroid tumors and adjacent non tumoral tissues of Ukrainian patients exposed or not to Chernobyl radioiodines

ABSTRACT: We compared the variations of expression of miRNA/small nucleolar RNA (snoRNA) in a series of post-Chernobyl tumors developed in patients exposed to radioactive iodines, at thyroid doses below (21 to 48 mGy) or above (0·58 to 2·5 Gy) the limit of significance of conventional epidemiology, and in a series of unexposed Ukrainian patients. We identified miRNA/snoRNA discriminating signatures of thyroid PTC etiology in function of the dose range (“Low doses” or “High doses”) or independent of the dose (“Low+High doses”), as compared to sporadic tumors. Moreover, corresponding signatures of radiation exposure were also found analysing the non-pathologic tissues adjacent to the tumors of exposed and non-exposed patients, which showed an overlap with the etiology signatures.

ORGANISM(S): Homo sapiens

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PROVIDER: E-MTAB-10094 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers. We profiled the transcriptomes of 11 primary PTCs with no detectable nodal invasion, 17 primary PTCs with nodal invasion and 17 patient-matched nodal metastases. We also profiled a number of control samples. These included 24 patient-matched normal thyroid tissues (11 from N0, 13 from N+ patients), and 4 normal lymph nodes; technical and biological replicates including additional nodal metastasis for 3 patients, adjacent blocks for 5 primary tumors, 4 normal thyroid tissues and 1 nodal metastasis.

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MiRNome/small RNA analysis of thyroid tumors and adjacent non tumoral tissues of Ukrainian patients exposed or not to Chernobyl radioiodines

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