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Background: Over 20% of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. We aimed to demonstrate the clinical and prognostic significance of thrombocytosis and hyperfibrinogenemia in high-grade serous ovarian cancer (HGSC)., Methods: We retrospectively investigated HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 in our institution. None of these patients had received neoadjuvant chemotherapy. Data, including age, performance status, FIGO stage, serum CA125, platelet count, fibrinogen level, and surgical residual disease, were collected. Thrombocytosis was defined as a platelet count greater than 450 × 10(9)/L, and hyperfibrinogenemia was defined as a fibrinogen level higher than 4.00 g/L. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For the multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which are expressed as hazard ratios (HRs)., Results: A total of 875 consecutive HGSC patients were identified. The median follow-up time was 29 (1-115) months. The median (interquartile range, IQR) preoperative platelet count was 301 (235-383) × 10(9)/L, and 121 (13.8%) women had thrombocytosis. The median (IQR) preoperative fibrinogen level was 3.85 (3.19-4.45) g/L, and 332 (45.9%) of the patients had hyperfibrinogenemia. Both preoperative thrombocytosis and hyperfibrinogenemia were associated with an advanced FIGO stage (p = 0.008 and <0.001, respectively), an increased CA125 level (p = 0.004 and 0.001, respectively), more extensive ascites (p < 0.001 and <0.001, respectively), more extensive residual disease (p < 0.001 and <0.001, respectively) and chemosensitivity (p = 0.043 and <0.001, respectively). In the univariate analyses, hyperfibrinogenemia was associated with reduced PFS (p < 0.001) and OS (p < 0.001). However, thrombocytosis was not found to be a potential predictor of PFS (P = 0.098) or OS (p = 0.894). In the multivariate analyses, hyperfibrinogenemia was an independent predictor of OS (p = 0.014) but not PFS (p = 0.062)., Conclusion: Preoperative thrombocytosis and hyperfibrinogenemia reflected tumor burden to some extent and thus influenced treatment outcomes, and the fibrinogen level was found to be useful as a prognostic predictor in the HGSC patients.

Background: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. Methods: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. Results: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). Conclusions: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients. [ABSTRACT FROM AUTHOR]

Background: Recent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis. Methods: We retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT). Results: In 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as "continuous-metastasis type", while the other 7 (13.7%) defined as "skip-metastasis type". Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3–63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that "continuous-metastasis type" had longer OS and PFS than "skip-metastasis type" (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among "continuous-metastasis type" patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors. Conclusions: In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as "continuous-metastasis type" with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected. [ABSTRACT FROM AUTHOR]

In the study of the deep learning classification of medical images, deep learning models are applied to analyze images, aiming to achieve the goals of assisting diagnosis and preoperative assessment. Currently, most research classifies and predicts normal and cancer cells by inputting single-parameter images into trained models. However, for ovarian cancer (OC), identifying its different subtypes is crucial for predicting disease prognosis. In particular, the need to distinguish high-grade serous carcinoma from clear cell carcinoma preoperatively through non-invasive means has not been fully addressed. This study proposes a deep learning (DL) method based on the fusion of multi-parametric magnetic resonance imaging (mpMRI) data, aimed at improving the accuracy of preoperative ovarian cancer subtype classification. By constructing a new deep learning network architecture that integrates various sequence features, this architecture achieves the high-precision prediction of the typing of high-grade serous carcinoma and clear cell carcinoma, achieving an AUC of 91.62% and an AP of 95.13% in the classification of ovarian cancer subtypes. [ABSTRACT FROM AUTHOR]

Introduction. Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods. In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results. TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion. Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of primary recurrence patterns on the prognosis of squamous cervical cancer after initial treatment. Methods: Primary recurrence patterns and prognostic factors were examined in stage IB-IIA cervical cancer patients after initial treatment. Recurrence site (locoregional recurrence and distant metastasis or in-field and out-field recurrence for patients receiving adjuvant radiotherapy) and subtype (nodal and organ recurrence) were examined. Clinicopathological characteristics and survival rates were evaluated to generate a prognostic nomogram. Results: A total of 472 patients were included. The median follow-up period, 5-year overall (OS) rate, and median OS were 59.1 months, 33.7%, and 24.0 months, respectively. Overall, 38.8% and 61.2% of the patients had locoregional recurrence and distant metastasis, respectively, and survival rates were comparable in these groups. Patients with nodal recurrence had better OS than those with organ recurrence (38.3% vs 30.7%, respectively; P = 0.001). Patients not receiving adjuvant radiotherapy had increased risk of pelvic recurrence [odds ratio (OR) = 0.148; 95% confidence interval[(CI): 0.075–0.291, P = 0.000]. Positive lymph-vascular space invasion (OR= 1.928; 95% CI: 1.151–3.229, P = 0.013) and no chemotherapy (OR = 0.521; 95% CI: 0.317–0.733, P = 0.040) increased the risk of distant metastasis. Positive lymph node status after initial treatment were associated with nodal recurrence (OR = 3.729; 95% CI: 1.838–7.563, P = 0.000), while elevated preoperative squamous cell carcinoma antigen (SCC-Ag) levels were associated with organ recurrence (OR = 1.642; 95% CI: 1.325–2.265, P = 0.002). Recurrence subtype, therapy for relapse, the International Federation of Gynecology and Obstetrics stage, adjuvant radiotherapy, preoperative SCC-Ag levels, and risk subgroup were independently associated with OS. Conclusions: Primary recurrence patterns were associated with specific clinicopathological characteristics of cervical cancer. Recurrent cervical cancer prognosis was mainly affected by recurrence location and subtype. [ABSTRACT FROM AUTHOR]

Objective. To determine whether the number of removed lymph nodes (RLN) is associated with survival in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIA cervical squamous cell carcinoma (CSCC). Methods. We reviewed the medical records of FIGO stage IB-IIA CSCC patients who underwent standardized radical hysterectomy with pelvic lymphadenectomy (RHPL) in our center between 2006 and 2014. The X-tile software was performed to calculate the optimal grouping of cutoff points for RLN. The impact of RLN on progression-free survival (PFS) and overall survival (OS) was analyzed using Cox regression analysis. Results. Among 3,127 patients, the mean number of RLN was 22, and positive lymph node (LN) was found in 668 (21.4%) patients. X-tile plots identified "21" and "16" as the optimal cutoff value of RLN to divide the patients into two groups in terms of PFS and OS separately. In all patients, the number of RLN was not associated with PFS (P = 0.182) or OS (P = 0.193). Moreover, in both LN positive and negative patients, the number of RLN was not associated with either PFS (P = 0.212 and P = 0.540 , respectively) or OS (P = 0.173 and P = 0.497 , respectively). Cox regression analysis showed that the number of RLN was not an independent prognostic factor for PFS or OS. Conclusion. If standardized RHPL was performed, the number of RLN was not an independent prognostic factor for survival of patients with FIGO stage IB-IIA CSCC. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to analyze the incidence, clinical characteristics, prognostic factors and survival of ovarian cancer patients with liver metastases upon initial diagnosis. Methods: Patients with ovarian cancer liver metastases upon initial diagnosis between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression was performed to identify the predictors of the presence of liver metastases in newly diagnosed ovarian cancer patients. Overall survival (OS) was assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression was conducted to determine the independent prognostic factors for OS. Results: A total of 1,744 ovarian cancer patients with liver metastases was identified from the SEER database, accounting for 6.7% of the entire ovarian cancer patients. As to the unique distant organ provided by SEER, liver was the most common metastatic site of ovarian cancer (4.65%). Age, race, laterality, histology, pathological grade, extrahepatic sites, stage of tumor were the predictors of the presence with liver metastases revealed by multivariable logistic regression model. Median OS for the patients with liver metastases at initial diagnosis of ovarian cancer was 16.0 months. Multivariate Cox regression model confirmed race, histology, extrahepatic metastatic sites, surgery and marital status were independent prognostic factors for OS. Conclusion: The study provided population-based estimates of the incidence and prognosis of newly diagnosed ovary cancer patients with liver metastases, which could be potentially used for the risk assessment and individualized treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ovarian clear cell carcinoma (CCC) is enriched in genes associated with glucose metabolism. OBJECTIVE: To evaluate the 18 F-FDG PET/CT-based metabolic variables and the correlations with clinicopathologic features in OCCC patients. METHODS: We measured quantitative parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). RESULTS: A total of 22 patients were included. PET/CT-based metabolic parameters were calculated for 20 patients because two had low glucose-uptake tumor. The median SUVmax was 7.25 (range 2.50–14.80). Spearman's correlation test revealed that the level of pre-operative serum cancer antigen 125 (CA 125) correlated significantly with MTV (P = 0.020) and TLG (P = 0.023). Interestingly, platinum-sensitive patients tended to have higher MTV/TLG though significance not achieved. On univariate analysis, the following four variables (stage, residual disease, platinum sensitivity and MTV50) were significant for both progression-free survival and overall survival. Besides, four metabolic parameters (MTV40, TLG40, TLG50 and TLG60) were significantly associated with patients' overall survival. Out of expectation, ovarian CCC patients with higher level of MTV/TLG tended to have better survival. CONCLUSIONS: 18 F-FDG PET/CT-based metabolic volumetric parameters might be predicators for survival in ovarian CCC patients. Cautions should be taken when interpreting the results due to the small sample size. [ABSTRACT FROM AUTHOR]

Background: Circulating extracelluar vesicles (EVs) in epithelial ovarian cancer (EOC) patients emanate from multiple cells. These EVs are emerging as a new type of biomarker as they can be obtained by non-invasive approaches. The aim of this study was to investigate circulating EVs from EOC patients and healthy women to evaluate their biological function and potential as diagnostic biomarkers.Methods: A quantitative proteomic analysis (iTRAQ) was applied and performed on 10 EOC patients with advanced stage (stage III-IV) and 10 controls. Twenty EOC patients and 20 controls were applied for validation. The candidate proteins were further validated in another 40-paired cohort to investigate their biomarker potential. Coagulation cascades activation was accessed by determining Factor X activity.Results: Compared with controls, 200 proteins were upregulated and 208 proteins were downregulated in the EOC group. The most significantly involved pathway is complement and coagulation cascades. ApoE multiplexed with EpCAM, plg, serpinC1 and C1q provide optimal diagnostic information for EOC with AUC = 0.913 (95% confidence interval (CI) =0.848-0.957, p < 0.0001). Level of activated Factor X was significantly higher in EOC group than control (5.35 ± 0.14 vs. 3.69 ± 0.29, p < 0.0001).Conclusions: Our study supports the concept of circulating EVs as a tool for non-invasive diagnosis of ovarian cancer. EVs also play pivotal roles in coagulation process, implying the inherent mechanism of generation of thrombus which often occurred in ovarian cancer patients at late stages. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), was associated with clinical characteristics and prognosis in patients with high-grade serous ovarian cancer (HGSC).Methods: We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. Preoperative PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count (per mm3). The optimal PNI cutoff value for overall survival (OS) was identified using the online tool "Cutoff Finder". Clinical characteristics and PNI were compared with chi-square or Fisher's exact tests, as appropriate. The impact of PNI on OS was analyzed using the Kaplan-Meier method and Cox proportional hazards model.Results: The median (range) PNI was 46.2 (29.2-67.7). The 45.45 cutoff value discriminated patients into the high-PNI and low-PNI groups. A low preoperative PNI was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, residual disease and platinum resistance. For univariate analyses, a high PNI was associated with increased OS (p < 0.001). In multivariate analyses, the PNI remained an independent predictor of OS as a continuous variable (p = 0.021) but not as dichotomized groups (p = 0.346).Conclusion: Our study demonstrated that the PNI could be a predictive and prognostic parameter for HGSC. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Background: There are no effective biomarkers for surveillance in ovarian clear cell carcinoma (OCCC), and the value of carbohydrate antigen 125 (CA-125) is limited. We sought to determine the value of both carbohydrate antigen 19-9 (CA19-9) and CA-125 levels postoperatively on the prognosis for OCCC. Methods: A total of 130 patients with OCCC who were consecutively treated by cytoreduction at Fudan University Shanghai Cancer Center were reviewed retrospectively. Univariate log-rank analyses and Cox regression multivariate analyses were performed to identify predictors of recurrence-free (RFS) and overall survival (OS) rates. Results: The survival in patients with postoperative normalization of CA-125 was significantly better than those with decreased but still elevated CA-125 (5-year RFS rates, 57.9% vs 45.2%, P = 0.046; 5-year OS rates, 81.4% vs 54.4%, P = 0.016), or those with increased CA-125 (5-year RFS rates, 57.9% vs 29.2%, P = 0.001; 5-year OS rates, 81.4% vs 33.6%, P < 0.001). An elevated level of postoperative CA-125 level was an independent risk factor for recurrence and survival [RFS: hazard ratio (HR), 2.2; P = 0.033; OS: HR, 4.3; P = 0.019]. Elevated postoperative CA19-9 was an independent risk factor for both RFS and OS in patients with normal postoperative CA-125 levels (RFS: HR, 5.0; P = 0.005; OS: HR, 1.1; P = 0.035). Conclusions: Combining postoperative CA19-9 and CA-125 appeared to be of great clinical value for prognosis in patients with OCCC after initial debulking. [ABSTRACT FROM AUTHOR]

Objective:The aim of our study is to investigate the expression pattern and prognostic significance of melanoma-associated antigens-A (MAGE-A) family in primary epithelial ovarian cancer (EOC) patients. Study design:The expression of MAGE-A family members, including MAGE-A1, -A2, -A3, -A4, -A6, -A10 and -A12 was immunohistochemically detected in 82 cases of primary EOC and 10 cases of pericarcinoma ovarian tissues. The association between MAGE-A family expression and the clinicopathological parameters as well as the prognosis of primary EOC patients was analyzed. Results:MAGE-A family expressed in 48.8% of primary EOC tissues, but not expressed in pericarcinoma ovarian tissues. MAGE-A expression was associated with the pathological types, FIGO stage, and pre-operative serum CA125 level. Overall survival of EOC patients with positive MAGE-A family expression was significantly shorter than those patients with negative MAGE-A expression. Multivariate analysis showed that although MAGE-A family expression can affect the overall survival, it was not an independent prognostic marker for EOC patients. Conclusions:Molecular assessment of MAGE-A family members could be helpful to improve the prognostic evaluation and to provide a new potential therapeutic target for primary EOC patients. 目的: 研究黑色素瘤相关抗原-A(MAGE-A)家族在原发性上皮性卵巢癌 (EOC) 中的表达形式与对预后的意义。 研究设计: MAGE-A家族成员包括MAGE-A1, -A2, -A3, -A4, -A6, -A10 和-A12。对82例原发性EOC和10例卵巢癌周围卵巢组织进行免疫组化检测。分析了MAGE-A家族的表达与临床病理参数及原发性EOC预后之间的关系。 结果: MAGE-A在原发性EOC组织中的表达率为48.8%, 但在卵巢癌周围卵巢组织中不表达。MAGE-A的表达与病理类型、FIGO分期和术前血清中CA125水平相关。MAGE-A家族表达阳性的EOC患者总生存期短于阴性表达的患者。多变量分析显示, 虽然MAGE-A家族的表达可影响总生存期, 但它对于EOC患者来说并不是一个独立预后指标。 结论: 在分子水平对MAGE-A家族进行评估有助于改善预后评估并且为原发性EOC患者提供了一个新的潜在治疗靶点。 [ABSTRACT FROM AUTHOR]

Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients’ clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS. [ABSTRACT FROM AUTHOR]

Aims: This study was conducted to investigate the association of vasculogenic mimicry (VM) formation and CD133 expression with the clinical outcomes of patients with ovarian cancer.Methods: This retrospective study was performed in 120 ovarian carcinoma samples. VM formation and CD133 expression was identified with CD31/periodic acid-Schiff double-staining and CD133 immunohistochemical staining. Collected clinical and pathological data included age at diagnosis, histologic type, tumor grade, tumor stage, lymph node metastases and response to chemotherapy. The overall survival time was calculated.Results: VM was identified in 52 (43%) of 120 ovarian carcinoma tissues and CD133 expression was found in 56 (47%) cases. Both VM formation and CD133 expression were associated with advanced tumor stage, high-grade carcinoma and non-response to chemotherapy (p < 0.05). They were also associated with shorter overall survival time (p < 0.05) by log-rank test. Combined marker of VM formation and CD133 expression was associated with high-grade ovarian carcinoma, late-stage disease, non-response to chemotherapy and shorter overall survival time (p < 0.05).Conclusions: VM formation and CD133 expression can provide additional prognostic information for patients with ovarian cancer. Combined marker of VM formation and CD133 expression may be a potent predictor for poor prognosis for patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective: We aimed to demonstrate the clinical and prognostic significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in high-grade serous ovarian cancer (HGSC). Methods: We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which were expressed as hazard ratios (HRs). Results: The NLRs ranged from 0.30 to 24.0. The median value was 3.24 and used as the cutoff value to discriminate between the high-NLR (≥3.24) and low-NLR (<3.24) groups. A high preoperative NLR level was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, worse cytoreduction outcome and chemoresistance. For univariate analyses, a high NLR was associated with reduced PFS (p<0.001) and OS (p<0.001). In multivariate analyses, a high NLR was still an independent predictor of PFS (p = 0.011), but not OS (p = 0.148). Conclusion: Our study demonstrated that NLR could reflect tumor burden and clinical outcomes to a certain extent and should be regarded as a predictive and prognostic parameter for HGSC. [ABSTRACT FROM AUTHOR]

Background: Over 20% of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. We aimed to demonstrate the clinical and prognostic significance of thrombocytosis and hyperfibrinogenemia in high-grade serous ovarian cancer (HGSC).Methods: We retrospectively investigated HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 in our institution. None of these patients had received neoadjuvant chemotherapy. Data, including age, performance status, FIGO stage, serum CA125, platelet count, fibrinogen level, and surgical residual disease, were collected. Thrombocytosis was defined as a platelet count greater than 450 × 10(9)/L, and hyperfibrinogenemia was defined as a fibrinogen level higher than 4.00 g/L. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For the multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which are expressed as hazard ratios (HRs).Results: A total of 875 consecutive HGSC patients were identified. The median follow-up time was 29 (1-115) months. The median (interquartile range, IQR) preoperative platelet count was 301 (235-383) × 10(9)/L, and 121 (13.8%) women had thrombocytosis. The median (IQR) preoperative fibrinogen level was 3.85 (3.19-4.45) g/L, and 332 (45.9%) of the patients had hyperfibrinogenemia. Both preoperative thrombocytosis and hyperfibrinogenemia were associated with an advanced FIGO stage (p = 0.008 and <0.001, respectively), an increased CA125 level (p = 0.004 and 0.001, respectively), more extensive ascites (p < 0.001 and <0.001, respectively), more extensive residual disease (p < 0.001 and <0.001, respectively) and chemosensitivity (p = 0.043 and <0.001, respectively). In the univariate analyses, hyperfibrinogenemia was associated with reduced PFS (p < 0.001) and OS (p < 0.001). However, thrombocytosis was not found to be a potential predictor of PFS (P = 0.098) or OS (p = 0.894). In the multivariate analyses, hyperfibrinogenemia was an independent predictor of OS (p = 0.014) but not PFS (p = 0.062).Conclusion: Preoperative thrombocytosis and hyperfibrinogenemia reflected tumor burden to some extent and thus influenced treatment outcomes, and the fibrinogen level was found to be useful as a prognostic predictor in the HGSC patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate whether EIF4A1, EIF4E, and EIF4G1 can serve as prognostic markers for patients with cervical cancer receiving preoperative brachytherapy.Tissue microarrays composed of 35 normal cervix samples, 87 cervical cancers treated without preoperative therapy, and 50 pairs of cervical cancer tissues collected before and after preoperative brachytherapy were constructed and evaluated for the expression of EIF4A1, EIF4E, and EIF4G using immunohistochemistry. Immunohistochemical staining was scored by the staining intensity and the percentages of tumor cells. The χ2 test was used to analyze the association between the immunohistochemistry results and clinicopathologic variables. The Kaplan-Meier method was applied to analyze the disease-specific survival.Overexpression of EIF4A1, EIF4E, and EIF4G1 were detected in 83.9%, 84.7%, and 80.3% of cervical cancers, respectively, all of which were significantly related to advanced International Federation of Gynecology and Obstetrics stage, squamous cell histology, lymph node metastasis, and deep stromal invasion (P < 0.05). The altered expression pattern of EIF4A1 and EIF4E after preoperative brachytherapy was significantly correlated with the cervical cancer response to brachytherapy (P = 0.029 and 0.012, respectively). The decreased expression of EIF4A1 predicted better tumor-specific survival (P = 0.02). The alteration of EIF4A1 was an independent predictor for tumor-specific survival (P = 0.047; hazards ratio, 0.272; 95% confidence interval, 0.076-0.982).Overexpression of EIF4A1, EIF4E, and EIF4G1 were acquired malignant phenotypic features of cervical cancer. EIF4A1 might function as a novel prognostic indicator and a potential therapeutic target for cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer.Objective: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy.Study Design: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental.Results: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery.Conclusion: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the prognostic factors for disease-free survival (DFS) and recurrence patterns in Chinese women with squamous cell carcinoma of the vulva treated with primary surgery. From 1980 through 2002, 100 patients with invasive squamous cell carcinoma of the vulva treated with primary surgery were included in this retrospective study. Survival analyses included the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. The 5- and 10-year DFS rates were 66.5% and 45.2%, respectively. Among all the tumor-related variables age, International Federation of Gynecology and Obstetrics stage, lymphovascular space invasion, and lymph node status were found to be significant predictors of DFS for the univariate analysis. Multivariate analysis proved that age (risk ratio, 6.572; 95% confidence interval, 1.759-24.546) and lymph nodes metastasis (risk ratio, 4.178; 95% confidence interval, 1.358-12.855) were the most significant prognostic factors of DFS (P < 0.05). The overall recurrence rate was 34.0% (34/100). Among the patients with recurrences, the locations of the recurrent disease were as follows: local recurrence in 20 (58.8%), groin recurrence in 2 (5.9%), local and groin in 1 (2.9%), distant metastases in 5 (14.7%), and local recurrence and distant metastases in 5 (14.7%); data were missing for 1 (2.9%) patients. Older age and lymph nodes metastases were the independent predictors of poor prognosis for patients with invasive squamous cell carcinoma of the vulva treated with primary surgery. Local recurrence was the main recurrence pattern after primary surgery which would be improved by multidisciplinary treatment. [ABSTRACT FROM AUTHOR]

We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3–189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3–54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST. • OYST tumor histology and residual lesions were independently associated with event free survival. • OYST histology, residual lesions and cycles to AFP normalization were independent risk factors for OYST overall survival. • Persistent and recurrent OYST demonstrated distinct molecular characteristics compared with primary OYST. • Persistent and recurrent OYST probably susceptible to immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

Gli proteins are key transcription factors of the Hedgehog (HH) signaling pathway, which is associated with tumorigenesis and drug resistance. However, the role of the HH signaling pathway in epithelial ovarian cancer (EOC) remains unclear. Studies have demonstrated that in some tumors, homeobox protein NANOG (NANOG), a known stem cell marker, is a downstream effector of Gli. However, limited research has been conducted on the association between Gli and NANOG in EOC, particularly regarding their roles in the tumor stemness, such as tumor development, drug resistance and patient prognosis. Thus, the aim of the present study was to explore the aforementioned issues. In this study, Gli1, Gli2 and NANOG expression in EOC tissues was assessed using immunohistochemistry. Gene expression was also assessed using western blotting and reverse transcription-quantitative PCR in SKOV3 cells treated with a Gli inhibitor and an HH agonist. Furthermore, cell proliferation, colony-forming ability and cisplatin sensitivity were assessed using Cell Counting Kit-8 and colony formation assays. The results showed that both Gli1 and NANOG were associated with cisplatin resistance and EOC disease stage, while the nuclear expression of Gli2 was significantly associated with cisplatin resistance. Together, the expression of Gli and NANOG predicted poor patient prognosis. Targeting Gli with GANT61 impeded tumor proliferation, reversed cisplatin resistance and colony formation, and reduced NANOG expression. To conclude, Gli and NANOG may be effective indicators of platinum resistance and prognosis in EOC. Targeting Gli may reduce the stemness of ovarian cancer cell, which may be achieved via indirect targeting of NANOG. [ABSTRACT FROM AUTHOR]

Background Prognostic markers are important for neurosurgeons to evaluate the indications for aggressive surgical management. The purpose of this study was to investigate whether the number of fractured calvarial bones could predict the outcome in patients with traumatic brain injury (TBI) after early craniotomy. Methods TBI patients who underwent early craniotomy were reviewed. The number of fractured calvarial bones was recorded by referring to preoperative computed tomographic (CT) images. Accordingly, patients were assigned to no calvarial fracture group, single calvarial fracture group, and multiple calvarial fractures group. Good outcome was defined as Glasgow Outcome Scale scores of 4 and 5 at discharge. Logistic regression analyses were used to assess the effect of calvarial fracture on outcome. A receiver operating characteristic curve was generated for the final model. Results In all, a total of 141 patients were enrolled. Patients with no calvarial fracture had a significantly lower rate of good outcome (12.5%) than did those with a single calvarial fracture (62.2%, P < 0.001) and those with multiple calvarial fractures (48.6%, P = 0.005). Binary logistic regression showed that the number of fractured calvarial bones was an independent imaging marker for predicting outcome ( P = 0.003) after adjustment for age, Glasgow Coma Scale score on admission, and decompressive craniectomy. The area under the curve of the final model was 0.863. Conclusions The number of fractured calvarial bones is an independent predictor of outcome in TBI patients after early craniotomy. No calvarial facture is associated with poor outcome in these patients. [ABSTRACT FROM AUTHOR]

Objective ERBB2 mutations have been found in a subset of invasive cervical cancer (ICC). Nevertheless, the prevalence, mutation spectrum, clinicopathological relevance, human papillomavirus (HPV)-genotype association and prognostic significance of ERBB2-mutated ICCs have not been well established. Methods In this study, ICC samples ( N = 1015) were assessed for mutations in ERBB2, KRAS, and PIK3CA by cDNA-based Sanger sequencing. Results Somatic ERBB2 mutations were detected in 3.15% patients. The ERBB2 mutation rate was significantly higher in adenocarcinoma (4.52%, 7/155), adenosquamous carcinoma (7.59%, 6/79) and neuroendocrine carcinoma (10.34%, 3/29) than that in squamous carcinoma (2.14%, 16/749) ( P = 0.004, Fisher exact test). In addition, 18.75% of the patients carrying ERBB2 mutations concomitantly harbored PIK3CA or KRAS mutations. Patients with ERBB2-mutated ICCs tended to have a worse prognosis than those with wild-type or PIK3CA-mutated ICCs but a better prognosis than those with KRAS-mutated ICCs. Conclusions This study provided a promising rationale for the clinical investigation of tyrosine kinase inhibitors for the treatment of cervical cancer with ERBB2 mutations. Patients with non-squamous cell carcinomas have priority as candidates for ERBB2-targeted therapy. Concurrent PIK3CA/RAS mutations should be considered in the design of clinical trials. [ABSTRACT FROM AUTHOR]

Objective The aim of our study was to investigate the prognostic influence of time to chemotherapy (TTC) in patients with high grade serous ovarian cancer (HGSC). Methods We retrospectively investigated 625 consecutive patients with HGSC who underwent primary staging or debulking surgery followed by platinum-based intravenous chemotherapy between April 2005 and June 2013 in our center. TTC was defined as the time interval between primary surgery and initiation of chemotherapy. Results The median (range) TTC was 15 (4–62) days. TTC was longer for patients who underwent bowel resection (p < 0.001). There were no differences in PFS and OS between patients initiating chemotherapy before and after 15 days (p = 0.604 and 0.826, respectively) or among 4 groups categorized by quartile values (< 10 days, 10–14 days, 15–20 days, or ≥ 21 days after surgery) (p = 0.471 and 0.516, respectively). When stratified by with and without residual disease, there were still no differences in PFS (p = 0.592 and 0.755, respectively) and OS (p = 0.962 and 0.640, respectively) between patients initiating chemotherapy before and after 15 days. In multivariate analyses, TTC was also not associated with PFS and OS categorized by median (p = 0.570 and 0.701, respectively), quartile values (p = 0.432, 0.194, 0.737 and 0.799, 0.290, 0.743, respectively) or integrated as a continuous variable (p = 0.550 and 0.430, respectively). Conclusion The time interval between surgery and chemotherapy seemed to have no prognostic impact on patients with HGSC within 6 weeks. [ABSTRACT FROM AUTHOR]