Clusterin (CLU), a multifunctional glycoprotein, is ubiquitously produced in mammalian tissues. CLU has been shown to play significant roles in many of the biological behaviours of human tumors, such as cell proliferation, apoptosis, chemoresistance and angiogenesis. However, the relationship of CLU expression with angiogenesis in ovarian cancer has not been studied. A total of 275 epithelial ovarian tumors were obtained from archives of paraffin‑embedded tissues. Immunohistochemical (IHC) staining for CLU and vascular endothelial growth factor (VEGF) was performed on a tissue microarray (TMA) including 181 primary ovarian epithelial cancer, 40 borderline ovarian tumors and 54 ovarian cancer mesenteric metastasis samples. Of the 174 cases, overexpression of CLU and VEGF were detected in 107 (61.5%) and 109 (62.9%) cases of primary ovarian carcinoma, respectively. Of the 107 cases of primary ovarian carcinoma with overexpression of CLU, expression of VEGF was increased in 82 (75.2%) cases. However, in another 67 cases without CLU overexpression, overexpression of VEGF was observed in only 27 (24.8%) cases (P<0.05). Overexpression of CLU in epithelial ovarian cancer appears to be correlated with increased tumor angiogenesis, consistent with the established role of CLU as an oncogene in the biology of ovarian cancer. In the treatment of ovarian cancer, these two markers may be used in the selection of patients for targeted therapy.
The prognosis for cervical cancer (CCa) patients with lymph node metastasis (LNM) is dismal. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa patients with LNM. However, the precise mechanism of LNM in CCa remains unclear. Herein, we demonstrated that protein tyrosine phosphatase receptor type M (PTPRM), identified from TCGA dataset, was markedly upregulated in CCa with LNM and correlated with LNM. Moreover, PTPRM was an independent prognostic factor of CCa patients in multivariate Cox′s proportional hazards model analysis and associated with poor prognosis. Furthermore, through gain-of-function and loss-of-function approaches, we found that PTPRM promoted CCa cells proliferation, migration, invasion, lymphangiogenesis, and LNM. Mechanistically, PTPRM promoted epithelial-mesenchymal transition (EMT) via Src-AKT signaling pathway and induced lymphangiogenesis in a VEGF-C dependent manner, resulting in LNM of CCa. Importantly, knockdown of PTPRM dramatically reduced LNM in vivo, suggesting that PTPRM plays an important role in the LNM of CCa. Taken together, our findings uncover a novel molecular mechanism in the LNM of CCa and identify PTPRM as a novel prognostic factor and potential therapeutic target for LNM in CCa.
Decreased protein expression of the TSLC1 gene might be important in conferring a more aggressive behavior in ovarian carcinoma. Thus, TSLC1 may be used as an independent prognostic molecular marker for patients with ovarian carcinoma.
A novel diagnostic nomogram based on age, CA125, FAR, MLR, and ultrasound result accurately predicts malignancy in patients with ovarian masses • This nomogram is easily accessible and has a higher diagnostic efficiency than ROMA, CPH-I, and RMI • Our model also has good diagnostic performance in patients with early-stage ovarian cancer
Although ovarian cancer, a gynecological malignancy, has the highest fatality rate, it still lacks highly specific biomarkers, and the differential diagnosis of ovarian masses remains difficult to determine for gynecologists. Our study aimed to obtain ovarian cancer-specific protein candidates from the circulating small extracellular vesicles (sEVs) and develop a protein panel for ovarian cancer screening and differential diagnosis of ovarian masses. In our study, sEVs derived from the serum of healthy controls and patients with cystadenoma and ovarian cancer were investigated to obtain a cancer-specific proteomic profile. In a discovery cohort, 1119 proteins were identified, and significant differences in the protein profiles of EVs were observed among groups. Then, 23 differentially expressed proteins were assessed using the parallel reaction monitoring in a validation cohort. Through univariate and multivariate logistic regression analyses, a novel model comprising three proteins (fibrinogen gamma gene (FGG), mucin 16 (MUC16), and apolipoprotein (APOA4)) was established to screen patients with ovarian cancer. This model exhibited an area under the receiver operating characteristic curve (AUC) of 0.936 (95% CI, 0.888–0.984) with 92.0% sensitivity and 82.9% specificity. Another panel comprising serum CA125, sEV-APOA4, and sEV-CD5L showed excellent performance (AUC 0.945 (95% CI, 0.890–1.000), sensitivity of 88.0%, specificity of 93.3%, and accuracy of 89.2%) to distinguish malignancy from benign ovarian masses. Altogether, our study provided a proteomic signature of circulating sEVs in ovarian cancer. The diagnostic proteomic panel may complement current clinical diagnostic measures for screening ovarian cancer in the general population and the differential diagnosis of ovarian masses.
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