{"title":"新型分子分型揭示了早期甲状腺乳头状癌患者的复发风险。","authors":"Mingyu Sun, Bingqing Zhao, Tao Chen, Lijun Yao, Xiaoxin Li, Shaojun Hu, Chengling Chen, Xinbao Gao, Chuangang Tang","doi":"10.1186/s13044-024-00193-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures.</p><p><strong>Patients and methods: </strong>The present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature.</p><p><strong>Results: </strong>Through screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084-0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363-83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group.</p><p><strong>Conclusions: </strong>These findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.</p>","PeriodicalId":39048,"journal":{"name":"Thyroid Research","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983671/pdf/","citationCount":"0","resultStr":"{\"title\":\"Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer.\",\"authors\":\"Mingyu Sun, Bingqing Zhao, Tao Chen, Lijun Yao, Xiaoxin Li, Shaojun Hu, Chengling Chen, Xinbao Gao, Chuangang Tang\",\"doi\":\"10.1186/s13044-024-00193-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Papillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures.</p><p><strong>Patients and methods: </strong>The present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature.</p><p><strong>Results: </strong>Through screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084-0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363-83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group.</p><p><strong>Conclusions: </strong>These findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.</p>\",\"PeriodicalId\":39048,\"journal\":{\"name\":\"Thyroid Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983671/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Thyroid Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s13044-024-00193-9\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thyroid Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s13044-024-00193-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
背景:甲状腺乳头状癌(PTC甲状腺乳头状癌(PTC)是一种轻度疾病,预后良好,但复发率高。我们的目的是利用多基因图谱对早期PTC患者的复发风险进行精确分层:本研究使用了癌症基因组图谱(TCGA)和多中心数据集的数据。采用无监督共识聚类获得最佳分子亚型,并进行最小绝对收缩和选择算子(LASSO)分析,以确定构建复发特征的潜在基因。卡普兰-梅耶生存分析和对数秩检验用于检测生存差异。Harrells 一致性指数(C-index)用于评估DNA损伤修复(DDR)复发特征的性能:结果:通过筛选8个候选基因集,根据DDR基因将整个队列成功分层为两个与复发相关的分子亚型:DDR-高亚型和DDR-低亚型:高DDR亚型和低DDR亚型。DDR-高亚型的复发率明显低于DDR-低亚型[HR = 0.288 (95%CI, 0.084-0.986), P = 0.047]。此外,还构建了包括PER1和EME2在内的双基因DDR复发特征。高风险组的无复发生存期(RFS)明显低于低风险组[HR = 10.647 (95%CI, 1.363-83.197), P = 0.024]。多中心数据显示,复发组中PER1和EME2低表达的患者比例高于非复发组:这些发现有助于准确、可靠地识别复发风险高的 PTC 患者,使他们能够接受更彻底、更积极的治疗策略和更严格的监测措施。
Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer.
Background: Papillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures.
Patients and methods: The present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature.
Results: Through screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084-0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363-83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group.
Conclusions: These findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.