Mitochondria play important roles in growth, signal transduction, division, tumorigenesis and energy metabolism in epithelial ovarian carcinomas (EOCs) without an effective biomarker. To investigate the proteomic profile of EOC mitochondrial proteins, a 6-plex isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial expressed proteins (mtEPs) in EOCs relative to controls, followed by an integrative analysis of the identified mtEPs and the Cancer Genome Atlas (TCGA) data from 419 patients. A total of 5115 quantified proteins were identified from purified mitochondrial samples, and 262 proteins were significantly related to overall survival in EOC patients. Furthermore, 63 proteins were identified as potential biomarkers for the development of an EOC, and our findings were consistent with previous reports on a certain extent. Pathway network analysis identified 70 signaling pathways. Interestingly, the results demonstrated that cancer cells exhibited an increased dependence on mitophagy, such as peroxisome, phagosome, lysosome, valine, leucine and isoleucine degradation and fatty acid degradation pathways, which might play an important role in EOC invasion and metastasis. Five proteins (GLDC, PCK2, IDH2, CPT2 and HMGCS2) located in the mitochondrion and enriched pathways were selected for further analysis in an EOC cell line and tissues, and the results confirmed reliability of iTRAQ proteomics. These findings provide a large-scale mitochondrial proteomic profiling with quantitative information, a certain number of potential protein biomarkers and a novel vision in the mitophagy bio-mechanism of a human ovarian carcinoma.
Na Li, Huanni Li, Lanqin Cao, and Xianquan Zhan
Hongqiang Wang, Rui Zhou, Li Sun, Jianling Xia, Xuchun Yang, Changqie Pan, Na Huang, Min Shi, Jianping Bin, Yulin Liao, and Wangjun Liao
Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I (TOP1MT) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues. TOP1MT knockdown significantly promoted GC migration and invasion in vitro and in vivo. Importantly, TOP1MT silencing increased glucose consumption, lactate production, glucose transporter 1 expression and the epithelial-mesenchymal transition (EMT) in GC. Additionally, regulation of glucose metabolism induced by TOP1MT was significantly associated with lactate dehydrogenase A (LDHA) expression. A retrospective analysis of clinical data from 295 patients with GC demonstrated that low TOP1MT expression was associated with lymph node metastasis, recurrence and high mortality rates. TOP1MT deficiency enhanced glucose aerobic glycolysis by stimulating LDHA to promote GC progression.
Guoliang Wang, Na Ren, Shengcai Wang, Xuexi Zhang, Yanzhen Li, Nian Sun, Qiaoyin Liu, Jie Zhang, Wenqi Song, and Xin Ni
It is uncertain whether serum TSH concentration is an independent risk factor for the malignancy of pediatric thyroid nodules. We sought the association of serum TSH concentration with the malignancy of pediatric thyroid nodules and with the characteristics of pediatric thyroid cancer. A total of 219 pediatric thyroid nodule patients were collected retrospectively for 5 consecutive years. The medical records collected included sex, age, serum TSH concentration, thyroid autoantibody status, thyroid ultra-sonography parameters, histological type, and pathological TNM stages. The serum TSH concentrations were compared between benign and malignant nodules or corresponding subgroups. Binary logistic regression analysis was used to evaluate the correlation of TSH concentration with the malignancy of thyroid nodules and with the characteristics of pediatric thyroid cancer. There was no significant difference in TSH concentration between benign nodule and thyroid cancer in total subjects and various subgroups. The serum TSH level was not correlated with the malignancy of thyroid nodules in univariate analysis, but negatively correlated with the malignancy of thyroid nodules (odds ratio = 0.856, P = 0.013) after adjusting for the patients’ sex, age, thyroid autoantibody status, and nodule size. The serum TSH level was not correlated with the tumor characteristics in pediatric thyroid cancer patients. In conclusion, the serum TSH concentration seems not to be a carcinogenic factor in pediatric thyroid nodule patients, nor to be an independent risk factor for characteristics of pre-existing pediatric thyroid cancers.