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Novel biomarker SYT12 may contribute to predicting papillary thyroid cancer outcomes.

ABSTRACT: Aim:To investigate biomarkers for predicting papillary thyroid cancer outcomes. Materials & methods:The expression of biomarkers (ITGA2, SYT12 and CDH3) was studied in a prospective cohort of patients with papillary thyroid cancer. Three outcomes of initial metastases, baseline status and longitudinal status were analyzed and correlated with the biomarkers. Results:SYT12 provided the best prediction of initial metastasis (sensitivity: 72%; specificity: 54%). SYT12 had the highest accuracy for predicting longitudinal status (sensitivity: 100%; specificity: 47%). The best performance for longitudinal status resulted from combining SYT12 with American Thyroid Association risk stratification, with sensitivity and specificity of 88 and 73%, respectively. Conclusion:SYT12 has some prognostic significance in papillary thyroid cancer. Further validation studies in larger populations are warranted.

SUBMITTER: Jonklaas J

PROVIDER: S-EPMC5729603 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Novel biomarker <i>SYT12</i> may contribute to predicting papillary thyroid cancer outcomes.

Jonklaas J J Murthy Srk S Liu D D Klubo-Gwiezdzinska J J Krishnan J J Burman K D KD Boyle L L Carrol N N Felger E E Loh Y P YP

Future science OA 20170922 1

<h4>Aim</h4>To investigate biomarkers for predicting papillary thyroid cancer outcomes.<h4>Materials & methods</h4>The expression of biomarkers (<i>ITGA2, SYT12</i> and <i>CDH3</i>) was studied in a prospective cohort of patients with papillary thyroid cancer. Three outcomes of initial metastases, baseline status and longitudinal status were analyzed and correlated with the biomarkers.<h4>Results</h4><i>SYT12</i> provided the best prediction of initial metastasis (sensitivity: 72%; specificity: ...[more]

PMID: 29255621

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Project description:Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown. Methods: A necroptosis-related gene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis. The predictive value of the prognostic signature was validated in an internal cohort. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was used to examine the relationships between necroptosis and immune cells, immunological functions, and immune checkpoints. Next, the modeled genes expressions were validated in 96 pairs of clinical tumor and normal tissue samples. Finally, the effects of modeled genes on PTC cells were studied by RNA interference approaches in vitro. Results: In this study, the risk signature of seven necroptosis-related genes was created to predict the prognosis of papillary thyroid cancer (PTC) patients, and all patients were divided into high- and low-risk groups. Patients in the high-risk group fared worse in terms of overall survival than those in the low-risk group. The area under the curve (AUC) of the receiving operating characteristic (ROC) curves proved the predictive capability of created signature. The risk score was found to be an independent risk factor for prognosis in multivariate Cox analysis. The low-risk group showed increased immune cell infiltration and immunological activity, implying that they might respond better to immune checkpoint inhibitor medication. Next, GEO database and qRT-PCR in 96 pairs of matched tumorous and non-tumorous tissues were used to validate the expression of the seven modeled genes in PTCs, and the results were compatible with TCGA database. Finally, overexpression of IPMK, KLF9, SPATA2 could significantly inhibit the proliferation, invasion and migration of PTC cells. Conclusion: The created necroptosis associated risk signature has the potential to have prognostic capability in PTC for patient outcome. The findings of this study could pave the way for further research into the link between necroptosis and tumor immunotherapy.

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Novel biomarker SYT12 may contribute to predicting papillary thyroid cancer outcomes.

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Novel biomarker <i>SYT12</i> may contribute to predicting papillary thyroid cancer outcomes.

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