卵巢癌在女性生殖系统恶性肿瘤中死亡率居首位,传统的手术和化疗对其生存率提高有限,免疫治疗是目前充满潜力的肿瘤治疗方式,卵巢癌有效免疫治疗的前提是对其免疫逃逸机制全面深刻的理解.卵巢癌的免疫逃逸机制包括卵巢癌相关抗原无法被识别、抗原递呈细胞的抑制、肿瘤杀伤性免疫细胞的抑制、免疫抑制细胞的激活等.
ObjectiveThe goal of this study was to find the risk factors for major intraoperative blood loss (MBL) of primary debulking surgery (PDS) for ovarian cancer.MethodsPatients with ovarian cancer who underwent PDS in our hospital, from 2010 to 2017, were enrolled. The association between risk factors and MBL was modeled with the use of logistic regression. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive value of the logistic regression model.ResultsA total of 346 patients met the inclusion criteria. There were 150 patients with MBL. Tumor stage 3/4 (P < 0.001), American Society of Anesthesiologists (ASA) score ≥3 (P = 0.044), ascites volume ≥500 ml (P = 0.002), radical or ultra-radical surgery (P = 0.002), and diabetes (P = 0.035) were independent risk factors for MBL in patients with ovarian cancer. The logistic regression combined model of these five factors is more reliable in the prediction of MBL with an area under the ROC curve of 0.729 than the tumor stage (ROC curve = 0.645) and surgical complexity (ROC curve = 0.568).ConclusionIn patients with ovarian cancer, five risk factors for major intraoperative bleeding were identified. Planned surgical procedures and preoperative risk factors can be used to predict perioperative blood requirements.
Background. RNPEPL1 (arginyl aminopeptidase-like 1) belongs to the M1 family of zinc metallopeptidases. We aimed to explore the role of RNPEPL1 in the occurrence and progression of ovarian carcinoma (OV). Methods: We analyzed the expression level and prognostic value of RNPEPL1 in OV across Oncomine, GEO, TCGA and Human Protein Atlas (HPA) database and identified its prognostic value by the Cox regression analysis and Kaplan–Meier method. We utilized GESA software to perform GO and KEGG analyses. We also utilized TIMER to evaluate the relevance between RNPEPL1 and tumor-infiltrating immune cells. Finally, relevance between RNPEPL1 and immune-related genes was examined by Pearson correlation analysis. Results: RNPEPL1 was overexpressed in OV tissues compared with normal ovary tissue. Moreover, high RNPEPL1 expression was related with poor OV survival in TCGA. Cox analyses suggested that overexpression of RNPEPL1 was an independent risk factor for overall survival(OS) of OV. Results of KEGG analysis suggested that genes were mainly enriched in T cell receptor signaling pathway, B cell receptor signaling pathway and natural killer cell mediated cytotoxicity when the expression level of RNPEPL1 is low. Besides, RNPEPL1 expression is associated with infiltrating levels of CD4+ T cells, B cells, macrophage, neutrophils and dendritic cells. And, the level of dendritic cells is correlated with OS of OV. RNPEPL1 expression was significantly correlated with the immune signaling pathway of antigen processing and presentation. Conclusions: RNPEPL1 is a novel independently prognostic biomarker of OV and was related to immune infiltration. Especially, the tight correlation between RNPEPL1 and antigen processing and presentation may be the potential hub of anti-tumor immunity and one of the essential factors influencing survival.
Background To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. Methods The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging. Results In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. Conclusions COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.
Objective We aimed to evaluate the ability of the fluorescent monoclonal antibody probe COC183B2-Cy7 (Cy7-conjugated COC183B2 antibody) to detect tiny metastatic lesions of ovarian cancer and thus guide precise tumor resection. Methods The expression of the tumor-associated antigen OC183B2 in lymph nodes and SKOV3-Luc cells was detected using immunohistochemistry and immunofluorescence. A subcutaneous mouse tumor model and an intraperitoneal ovarian cancer metastasis model were constructed using SKOV3-Luc cells. Near-infrared fluorescence (NIRF) imaging was performed to determine the imaging parameters and evaluate the ability of COC183B2-Cy7 to detect tiny metastatic lesions. Results OC183B2 was expressed in metastatic lymph nodes and SKOV3-Luc cells. NIRF imaging of the subcutaneous mouse tumor model showed that the tumor background ratio was significantly higher in the COC183B2-Cy7 group than in the control group at different time points postinjection. Biodistribution study showed that COC183B2-Cy7 did not accumulate in other organs. COC183B2-Cy7 can detect tiny metastatic lesions of ovarian cancer. The smallest intraperitoneal metastatic tumor detected by COC183B2-Cy7 was approximately 1 mm. Conclusions COC183B2-Cy7 probe has relatively high specificity and sensitivity. Our study suggests that COC183B2-Cy7 probe is a promising diagnostic tool for the complete and accurate resection of malignant lesions in fluorescence-guided surgery.
The study aimed to investigate the prognostic value of preoperative hematocrit (HCT) on the survival of epithelial ovarian cancer (EOC) patients. Patients who underwent primary debulking surgery (PDS) in our institution, from January 2010 to December 2015, were enrolled. The preoperative HCT, hemoglobin (Hb), tumor stage, ascites volume, age, albumin, BMI, ASA score, diabetes and other factors were collected and analyzed to find the risk factors for poor prognosis of EOC patients using Cox regression. Survival analysis was conducted with Kaplan–Meier method and log-rank test. 192 patients met the inclusion criteria. HCT < 35% (P = 0.031, HR: 1.715, 95% CI 1.050–2.802) was an independent risk factor for poor overall survival in patients. The mean survival time was 83.7 months in patients with preoperative HCT ≥ 35% and 61.7 months in patients with HCT < 35% (P = 0.002). Patients with low HCT (< 35%) had a poor prognosis compared with patients with normal HCT, specifically in the patients of stage III/IV, age ≥ 65 years, BMI ≥ 25.0 kg/m2, ascites volume ≤ 500 mL, ASA score < 3, albumin ≥ 35 g/L and nondiabetic. Low HCT was more likely to occur in patients with advanced stage (III/IV), anemia (Hb < 110 g/mL), low albumin (< 35 g/L), high ASA score (≥ 3) and platelet > 400 × 109/L. Preoperative low HCT was a valuable predictor for EOC patients’ poor prognosis, specifically in obese, nondiabetic, elder, advanced stage but having relatively good performance status patients.
在妇科恶性肿瘤中,卵巢癌死亡率居首.老年卵巢癌患者数量占很大比例.与年轻卵巢癌患者相比,老年患者合并症多、手术耐受性差、化疗毒副反应较重,总体预后更差.如何制定出针对老年卵巢癌患者合理有效的治疗方案成为了亟待解决的问题.老年卵巢癌患者化疗主要问题包括化疗药毒性大,患者耐受性差,初始化疗推迟,经常需要减少剂量或者化疗延迟,全疗程完成率低等.老年卵巢癌患者的手术也存在手术入选率低,术后并发症和术后死亡率高的问题.卵巢癌的最佳治疗方案是首次肿瘤细胞减灭术和及时化疗,通过回顾老年卵巢癌患者化疗与手术治疗中存在的问题,显示老年卵巢癌患者化疗及手术治疗前的评估十分重要.老年卵巢癌患者可应用新辅助化疗.通过有效评估制定出合理的化疗方案和手术范围才能更好地提高老年卵巢癌患者的生存期及生活质量.