Identification and validation of an immune-related prognostic signature and key gene in papillary thyroid carcinoma.
Identification and validation of an immune-related prognostic signature and key gene in papillary thyroid carcinoma.
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甲状腺乳头状癌免疫相关预后特征和关键基因的鉴定和验证
DOI：
10.1186/s12935-021-02066-9
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发表时间：
2021-07-15
影响因子：
5.8
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Qin R;Li C;Wang X;Zhong Z;Sun C
甲状腺乳头状癌（PTC）是甲状腺癌最常见的病理类型。对于复发、转移及放射性碘抵抗的患者，传统抗肿瘤治疗效果并不理想。免疫相关基因（IRGs）的异常表达在PTC的发病机制中起着关键作用。然而，IRGs对PTC预后的影响仍不明确。
基于癌症基因组图谱（TCGA）和ImmPort数据库，我们整合了PTC患者的IRG表达谱和无进展生存期（PFIs）。首先，我们确定了PTC中差异表达的IRGs和转录因子（TFs）。随后，通过对TCGA中差异表达的IRGs进行单因素Cox回归、最小绝对收缩和选择算子（LASSO）回归以及多因素Cox回归分析，构建了一个可预测PFI的IRG模型。此外，蛋白质 - 蛋白质相互作用（PPI）网络展示了差异表达基因（DEGs）之间的相互作用，并从该网络中提取了度值最高的前30个基因。然后，通过PPI网络与单因素Cox回归的交叉分析确定关键IRG，并通过蛋白质免疫印迹法和免疫组织化学（IHC）验证其差异表达。进行单样本基因集富集分析（ssGSEA）以了解关键IRG表达水平与免疫活性之间的相关性。
在PTC患者中共鉴定出355个差异表达的IRGs和43个差异表达的TFs。最终利用8个IRGs构建了一个IRG模型。在训练集中，该IRG模型在1年、3年和5年时的曲线下面积（AUCs）分别达到0.948、0.820和0.831。此外，乳铁蛋白（LTF）被确定为与预后相关的关键IRG。肿瘤组织中LTF的表达水平显著低于正常组织。并且ssGSEA结果显示LTF的表达水平与免疫活性密切相关。
这些研究结果表明，该预后模型和关键IRG可能成为有前景的PTC患者预后分子标志物。
BackgroundPapillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. The effect of traditional anti-tumor therapy is not ideal for the patients with recurrence, metastasis and radioiodine resistance. The abnormal expression of immune-related genes (IRGs) has critical roles in the etiology of PTC. However, the effect of IRGs on PTC prognosis remains unclear.MethodsBased on The Cancer Genome Atlas (TCGA) and ImmPort databases, we integrated IRG expression profiles and progression-free intervals (PFIs) of PTC patients. First, we identified the differentially expressed IRGs and transcription factors (TFs) in PTC. Subsequently, an IRG model that can predict the PFI was constructed by using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses of the differentially expressed IRGs in the TCGA. Additionally, a protein–protein interaction (PPI) network showed the interactions between the differentially expressed genes (DEGs), and the top 30 genes with the highest degree were extracted from the network. Then, the key IRG was identified by the intersection analysis of the PPI network and univariate Cox regression, which was verified the differential expression of by western blotting and immunohistochemistry (IHC). ssGSEA was performed to understand the correlation between the key IRG expression level and immune activity.ResultsA total of 355 differentially expressed IRGs and 43 differentially expressed TFs were identified in PTC patients. Then, eight IRGs were finally utilized to construct an IRG model. The respective areas under the curve (AUCs) of the IRG model reached 0.948, 0.820, and 0.831 at 1, 3 and 5 years in the training set. In addition, lactotransferrin (LTF) was determined as the key IRG related to prognosis. The expression level of LTF in tumor tissues was significantly lower than that in normal tissues. And the results of ssGSEA showed the expression level of LTF is closely related to immune activity.ConclusionsThese findings show that the prognostic model and key IRG may become promising molecular markers for the prognosis of PTC patients.
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影响因子：
8.8
作者：
Gunda V;Gigliotti B;Ndishabandi D;Ashry T;McCarthy M;Zhou Z;Amin S;Freeman GJ;Alessandrini A;Parangi S
通讯作者：
Parangi S
影响因子：
3.7
作者：
González-Foruria I;Santulli P;Chouzenoux S;Carmona F;Batteux F;Chapron C
通讯作者：
Chapron C
影响因子：
--
作者：
George N;Agarwal A;Kumari N;Agarwal S;Krisnani N;Gupta SK
通讯作者：
Gupta SK
影响因子：
7.3
作者：
Kruzel ML;Zimecki M;Actor JK
通讯作者：
Actor JK
DOI：
10.1016/s1470-2045(14)71116-7
发表时间：
2015-04
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Balachandran VP;Gonen M;Smith JJ;DeMatteo RP
通讯作者：
DeMatteo RP