Aside from tumor cells, ovarian cancer-related ascites contains the immune components. The aim of this study was to evaluate whether a combination of clinical and immunological parameters can predict survival in patients with ovarian cancer. Ascites specimens and medical records from 144 ovarian cancer patients at our hospital were used as the derivation group to select target clinical and immunological factors to generate a risk-scoring system to predict patient survival. Eighty-two cases from another hospital were used as the validation group to evaluate this system. The surgical status and expression levels of interleukin 17a (IL17a) and IL21 in ascites were selected for the risk-scoring system in the derivation group. The areas under the receiver operating characteristic (AUROC) curves of the overall score for disease-free survival (DFS) of the ovarian cancer patients were 0.84 in the derivation group, 0.85 in the validation group, and 0.84 for all the patients. The AUROC curves of the overall score for overall survival (OS) of cases were 0.78 in the derivation group, 0.76 in the validation group, and 0.76 for all the studied patients. Good correlations between overall risk score and survival of the ovarian cancer patients were demonstrated by sub-grouping all participants into four groups (P for trend <0.001 for DFS and OS). Therefore, acombination of clinical and immunological parameters can provide a practical scoring system to predict the survival of patients with ovarian carcinoma. IL17a and IL21 can potentially be used as prognostic and therapeutic biomarkers.
Yu-Li Chen, Cheng-Yang Chou, Ming-Cheng Chang, Han-Wei Lin, Ching-Ting Huang, Shu-Feng Hsieh, Chi-An Chen, and Wen-Fang Cheng
Jeong Won Park, Cho Rong Han, Li Zhao, Mark C Willingham, and Sheue-yann Cheng
Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (Thrb PV/PV Pten +/− mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. WT and Thrb PV/PV Pten +/− mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated Thrb PV/PV Pten +/− mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated Thrb PV/PV Pten +/− mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer.
Han-Wei Lin, Ying-Cheng Chiang, Nai-Yun Sun, Yu-Li Chen, Chi-Fang Chang, Yi-Jou Tai, Chi-An Chen, and Wen-Fang Cheng
The role of chitinase-3-like protein 1 (CHI3L1) in ovarian cancer and the possible mechanisms were elucidated. CHI3L1 is a secreted glycoprotein and associated with inflammation, fibrosis, asthma, extracellular tissue remodeling and solid tumors. Our previous study showed CHI3L1 could be a potential prognostic biomarker for epithelial ovarian cancer and could protect cancer cells from apoptosis. Therefore, clinical data and quantitation of CHI3L1 of ovarian cancer patients, tumor spheroid formation, side-population assays, Aldefluor and apoptotic assays, ELISA, RT-PCR, immunoblotting and animal experiments were performed in two ovarian cancer cells lines, OVCAR3 and CA5171, and their CHI3L1-overexpressing and -knockdown transfectants. High expression of CHI3L1 was associated with poor outcome and chemoresistance in ovarian cancer patients. The mRNA expression of CHI3L1 in CA5171 ovarian cancer stem-like cells was 3-fold higher than in CA5171 parental cells. CHI3L1 promoted the properties of ovarian cancer stem-like cells including generating more and larger tumor spheroids and a higher percentage of ALDH+ in tumor cells and promoting resistance to cytotoxic drug-induced apoptosis. CHI3L1 could induce both the Akt (essential) and Erk signaling pathways, and then enhance expression of β-catenin followed by SOX2, and finally promote tumor spheroid formation and other properties of ovarian cancer stem-like cells. OVCAR3 CHI3L1-overexpressing transfectants were more tumorigenic in vivo, whereas CA5171 CHI3L1-knockdown transfectants were not tumorigenic in vivo. CHI3L1 critically enhances the properties of ovarian cancer stem-like cells. CHI3L1 or CHI3L1-regulated signaling pathways and molecules could be potential therapeutic targets in ovarian cancer.
Yang-Hsiang Lin, Meng-Han Wu, Ya-Hui Huang, Chau-Ting Yeh, Hsiang-Cheng Chi, Chung-Ying Tsai, Wen-Yu Chuang, Chia-Jung Yu, I-Hsiao Chung, Ching-Ying Chen, and Kwang-Huei Lin
Thyroid hormone (T3) and its receptor (TR) are involved in cancer progression. While deregulation of long non-coding RNA (lncRNA) expression has been detected in many tumor types, the mechanisms underlying specific involvement of lncRNAs in tumorigenicity remain unclear. Experiments from the current study revealed negative regulation of BC200 expression by T3/TR. BC200 was highly expressed in hepatocellular carcinoma (HCC) and effective as an independent prognostic marker. BC200 promoted cell growth and tumor sphere formation, which was mediated via regulation of cell cycle-related genes and stemness markers. Moreover, BC200 protected cyclin E2 mRNA from degradation. Cell growth ability was repressed by T3, but partially enhanced upon BC200 overexpression. Mechanistically, BC200 directly interacted with cyclin E2 and promoted CDK2–cyclin E2 complex formation. Upregulation of cell cycle-related genes in hepatoma samples was positively correlated with BC200 expression. Our collective findings support the utility of a potential therapeutic strategy involving targeting of BC200 for the treatment of HCC.
Fei Han, Wen-bin Liu, Jian-jun Li, Ming-qian Zhang, Jun-tang Yang, Xi Zhang, Xiang-lin Hao, Li Yin, Cheng-yi Mao, Xiao Jiang, Jia Cao, and Jin-yi Liu
New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31–5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial–mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.