Gender-and age-related differential genes and pathways in cervical lymph node metastasis of papillary thyroid carcinoma
10.7659/j.issn.1005-6947.2024.11.009
- VernacularTitle:甲状腺乳头状癌颈部淋巴转移的性别与年龄相关差异基因与通路分析
- Author:
Bingfeng CHU
1
;
Yingjun HU
Author Information
1. 上海交通大学医学院附属新华医院普通外科,上海 200092
- Publication Type:Journal Article
- Keywords:
Thyroid Neoplasms;
Thyroid Cancer,Papillary;
Lymphatic Metastasis;
Risk Factors
- From:
Chinese Journal of General Surgery
2024;33(11):1825-1834
- CountryChina
- Language:Chinese
-
Abstract:
Background and Aims:Thyroid cancer is the most common malignant tumor of the endocrine system,with papillary thyroid carcinoma (PTC) being the predominant subtype. PTC mainly metastasizes via cervical lymph nodes. Clinical observations and some studies have indicated that young male PTC patients are more prone to cervical lymph node metastasis. This study aims to analyze the risk factors for cervical lymph node metastasis and explore the differentially expressed genes and associated signaling pathways in PTC patients across different genders and age groups.Methods:The clinical data of PTC patients who underwent surgical treatment at the Department of General Surgery,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,and the Huangpu Branch of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from January 2015 to October 2018 were collected. Risk factors for cervical lymph node metastasis were analyzed. The TCGA database was used to identify differentially expressed genes and related pathways in male and ≤45-year-old PTC patients compared to their female and>45-year-old counterparts,respectively. Functional validation of selected differentially expressed genes was performed in cellular studies. Results:A total of 1071 PTC patients were included,of whom 209 (19.5％) had cervical lymph node metastasis. Univariate analysis showed that male patients had a higher rate of cervical lymph node metastasis than female patients (x2=5.990,P<0.05),and patients ≤45 years old had a higher metastasis rate than those>45 years old (x2=28.969,P<0.05). Multivariate analysis identified male gender and age ≤45 years as independent risk factors for cervical lymph node metastasis (both P<0.05). A total of 443 and 477 differentially expressed genes were identified in male and ≤45-year-old PTC patients,respectively,using the TCGA database. GO analysis revealed that the differentially expressed genes in these patients were primarily enriched in immune-related biological processes,such as complement activation via the classical pathway and immunoglobulin-mediated humoral immune response. KEGG pathway analysis indicated that these differentially expressed genes were associated with metabolic pathways,including pancreatic secretion,thyroid hormone synthesis,and fat digestion and absorption. Based on fold-change and pathway analysis,IGF2 and IGF2BP1 were selected for functional validation. Knockdown of IGF2 and IGF2BP1 significantly reduced the migration ability of thyroid cancer cell lines BCPAP and KTC-1 (both P<0.05). Conclusion:Male gender and age ≤45 years are independent risk factors for cervical lymph node metastasis in PTC. The underlying mechanisms may involve multiple immune-related or endocrine metabolism-associated signaling pathways,highlighting the need for more rigorous examination and management of cervical lymph nodes in young male patients. Further research on IGF2 and IGF2BP1 may provide new therapeutic targets for thyroid cancer and cervical lymph node metastasis.
