基于焦亡相关基因的甲状腺乳头状癌诊断模型的构建与验证：一项生物信息学及体外研究

Development and Verification of Diagnosis Model for Papillary Thyroid Cancer Based on Pyroptosis-Related Genes: A Bioinformatic and in vitro Investigation.

作者信息

Ding Lingling, Zheng Guowan, Zhou Aoni, Song Fahuan, Zhu Lei, Cai Yefeng, Guo Yehao, Hua Tebo, Liu Yunye, Ma Wenli, Hu Yiqun, Guo Yawen, Zheng Chuanming

机构信息

Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People's Republic of China.

Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, Zhejiang, 310000, People's Republic of China.

出版信息

J Inflamm Res. 2024 Oct 29;17:7761-7776. doi: 10.2147/JIR.S478989. eCollection 2024.

DOI:10.2147/JIR.S478989

PMID:39494207

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11531300/

Abstract

BACKGROUND

The incidence of papillary thyroid cancer (PTC) has been increasing annually; however, early diagnosis can improve patient outcomes. Pyroptosis is a programmed cell death modality that has received considerable attention recently. However, no studies have reported using pyroptosis-related genes in PTC diagnosis.

METHODS

Analyzed 33 pyroptosis-related genes in PTC transcriptome data from the Gene Expression Omnibus database. Subsequently, used the Least Absolute Shrinkage and Selection Operator (LASSO) model to construct a PTC molecular diagnostic model. Furthermore, confirmed differences in the expression of five genes between PTC and non-tumor tissues using immunohistochemistry. Collected 338 PTC and control samples to construct a five-gene PTC diagnostic model, which was then validated using a training set and underwent correlation analysis with immune cell infiltration. Additionally, validated the biological functions of the core gene NOD1 in vitro.

RESULTS

The five-gene PTC diagnostic model demonstrated good diagnostic value for PTC. Moreover, identified three reliable subtypes of pyroptosis and found that NOD1 is involved in tumor-suppressive microenvironment formation. Notably, patients with high NOD1 expression had lower Progression-Free Survival (PFS). Additionally, NOD1 expression was positively correlated with immune markers such as CD47, CD68, CD3, and CD8. Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro.

CONCLUSION

Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.

摘要

背景

甲状腺乳头状癌（PTC）的发病率逐年上升；然而，早期诊断可改善患者预后。细胞焦亡是一种程序性细胞死亡方式，最近受到了广泛关注。然而，尚无研究报道将细胞焦亡相关基因用于PTC诊断。

方法

分析了基因表达综合数据库中PTC转录组数据中的33个细胞焦亡相关基因。随后，使用最小绝对收缩和选择算子（LASSO）模型构建PTC分子诊断模型。此外，通过免疫组织化学证实了PTC与非肿瘤组织中5个基因表达的差异。收集338份PTC和对照样本构建五基因PTC诊断模型，然后使用训练集进行验证，并与免疫细胞浸润进行相关性分析。另外，在体外验证了核心基因NOD1的生物学功能。

结果

五基因PTC诊断模型对PTC具有良好的诊断价值。此外，确定了三种可靠的细胞焦亡亚型，发现NOD1参与肿瘤抑制微环境的形成。值得注意的是，NOD1高表达的患者无进展生存期（PFS）较低。此外，NOD1表达与CD47、CD68、CD3和CD8等免疫标志物呈正相关。最后，抑制NOD1在体外显示出显著的抗PTC活性。