Ruiwang Xie: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Junyu Lin: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Weiwei Li: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Huaying Chen: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Junsi Zhang: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Minjie Zhong: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Jiajie Xue: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Caiqin Mo: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Ling Chen: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Youzhi Zhu: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Thyroid and Breast Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China. Electronic address: zhu@fjmu.edu.cn.
Xiangjin Chen: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Thyroid and Breast Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China. Electronic address: rjbhcxj@fjmu.edu.cn.
Sunwang Xu: Department of Thyroid and Breast Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Thyroid and Breast Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Provincial Key Laboratory of Precision Medicine for Cancer, Fuzhou, China. Electronic address: xusw1206@163.com.
Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.
