Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.

Aberrant expressions of apoptotic genes have been associated with papillary thyroid carcinoma (PTC) in the past, however, their prognostic role and utility as biomarkers remains poorly understood. In this study, we analysed 505 PTC patients by employing Cox-PH regression techniques, prognostic index...

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Autores principales:	Chakit Arora, Dilraj Kaur, Leimarembi Devi Naorem, Gajendra P S Raghava
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c48ec4f168d94696b50186f142e629ab
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spelling	oai:doaj.org-article:c48ec4f168d94696b50186f142e629ab2021-12-02T20:13:14ZPrognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.1932-620310.1371/journal.pone.0259534https://doaj.org/article/c48ec4f168d94696b50186f142e629ab2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259534https://doaj.org/toc/1932-6203Aberrant expressions of apoptotic genes have been associated with papillary thyroid carcinoma (PTC) in the past, however, their prognostic role and utility as biomarkers remains poorly understood. In this study, we analysed 505 PTC patients by employing Cox-PH regression techniques, prognostic index models and machine learning methods to elucidate the relationship between overall survival (OS) of PTC patients and 165 apoptosis related genes. It was observed that nine genes (ANXA1, TGFBR3, CLU, PSEN1, TNFRSF12A, GPX4, TIMP3, LEF1, BNIP3L) showed significant association with OS of PTC patients. Five out of nine genes were found to be positively correlated with OS of the patients, while the remaining four genes were negatively correlated. These genes were used for developing risk prediction models, which can be utilized to classify patients with a higher risk of death from the patients which have a good prognosis. Our voting-based model achieved highest performance (HR = 41.59, p = 3.36x10-4, C = 0.84, logrank-p = 3.8x10-8). The performance of voting-based model improved significantly when we used the age of patients with prognostic biomarker genes and achieved HR = 57.04 with p = 10-4 (C = 0.88, logrank-p = 1.44x10-9). We also developed classification models that can classify high risk patients (survival ≤ 6 years) and low risk patients (survival > 6 years). Our best model achieved AUROC of 0.92. Further, the expression pattern of the prognostic genes was verified at mRNA level, which showed their differential expression between normal and PTC samples. Also, the immunostaining results from HPA validated these findings. Since these genes can also be used as potential therapeutic targets in PTC, we also identified potential drug molecules which could modulate their expression profile. The study briefly revealed the key prognostic biomarker genes in the apoptotic pathway whose altered expression is associated with PTC progression and aggressiveness. In addition to this, risk assessment models proposed here can help in efficient management of PTC patients.Chakit AroraDilraj KaurLeimarembi Devi NaoremGajendra P S RaghavaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259534 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chakit Arora Dilraj Kaur Leimarembi Devi Naorem Gajendra P S Raghava Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
description	Aberrant expressions of apoptotic genes have been associated with papillary thyroid carcinoma (PTC) in the past, however, their prognostic role and utility as biomarkers remains poorly understood. In this study, we analysed 505 PTC patients by employing Cox-PH regression techniques, prognostic index models and machine learning methods to elucidate the relationship between overall survival (OS) of PTC patients and 165 apoptosis related genes. It was observed that nine genes (ANXA1, TGFBR3, CLU, PSEN1, TNFRSF12A, GPX4, TIMP3, LEF1, BNIP3L) showed significant association with OS of PTC patients. Five out of nine genes were found to be positively correlated with OS of the patients, while the remaining four genes were negatively correlated. These genes were used for developing risk prediction models, which can be utilized to classify patients with a higher risk of death from the patients which have a good prognosis. Our voting-based model achieved highest performance (HR = 41.59, p = 3.36x10-4, C = 0.84, logrank-p = 3.8x10-8). The performance of voting-based model improved significantly when we used the age of patients with prognostic biomarker genes and achieved HR = 57.04 with p = 10-4 (C = 0.88, logrank-p = 1.44x10-9). We also developed classification models that can classify high risk patients (survival ≤ 6 years) and low risk patients (survival > 6 years). Our best model achieved AUROC of 0.92. Further, the expression pattern of the prognostic genes was verified at mRNA level, which showed their differential expression between normal and PTC samples. Also, the immunostaining results from HPA validated these findings. Since these genes can also be used as potential therapeutic targets in PTC, we also identified potential drug molecules which could modulate their expression profile. The study briefly revealed the key prognostic biomarker genes in the apoptotic pathway whose altered expression is associated with PTC progression and aggressiveness. In addition to this, risk assessment models proposed here can help in efficient management of PTC patients.
format	article
author	Chakit Arora Dilraj Kaur Leimarembi Devi Naorem Gajendra P S Raghava
author_facet	Chakit Arora Dilraj Kaur Leimarembi Devi Naorem Gajendra P S Raghava
author_sort	Chakit Arora
title	Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
title_short	Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
title_full	Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
title_fullStr	Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
title_full_unstemmed	Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
title_sort	prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c48ec4f168d94696b50186f142e629ab
work_keys_str_mv	AT chakitarora prognosticbiomarkersforpredictingpapillarythyroidcarcinomapatientsathighriskusingninegenesofapoptoticpathway AT dilrajkaur prognosticbiomarkersforpredictingpapillarythyroidcarcinomapatientsathighriskusingninegenesofapoptoticpathway AT leimarembidevinaorem prognosticbiomarkersforpredictingpapillarythyroidcarcinomapatientsathighriskusingninegenesofapoptoticpathway AT gajendrapsraghava prognosticbiomarkersforpredictingpapillarythyroidcarcinomapatientsathighriskusingninegenesofapoptoticpathway
_version_	1718374790421544960

Prognostic biomarkers for predicting papillary thyroid carcinoma patients at high risk using nine genes of apoptotic pathway.

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