Objective In clinical practice, gynecologic oncologists are interested in predicting the prognosis of patients through information from different sources. Recently, the overall survival (OS) of ovarian cancer patients has been widely and intensively researched, and a large number of risk factors have been determined, including the biomarker of cancer antigen 125 (CA-125). For newly diagnosed patients, it is critical to construct effective prognostic models to predict prognosis dynamically by combining their CA-125 values with adjusted clinical factors. Methods/Materials A total of 227 ovarian cancer participants entered this study. A 4-step method was used to construct a joint model to examine the association between longitudinal CA-125 measurements and OS time, to explore time-independent predictive factors influencing OS, and to obtain an accurate and credible dynamic prediction of OS for specific subjects. Results We found that CA-125 values were greatly affected by observation time, menarche, Federation International of Gynecology and Obstetrics stage, and ascites at baseline. Similarly, CA-125 values, menopause, Federation International of Gynecology and Obstetrics stage, and surgery state at baseline were selected from the best Cox proportion hazard model and showed a strong correlation with OS. In addition, the analyses presented by the joint model depict that, as time goes by, increasing CA-125 was deemed to be a significant predictor of death. Conclusions Together, our results show that a joint model could be highly efficient in clinical consultation and diagnosis for patients newly diagnosed as having ovarian cancer. Longitudinal CA-125 values, which are measured over time, can be used to credibly predict OS after taking all adjusted covariates into account.
Objective High-grade serous ovarian cancer (HGSOC) accounts for approximately 70% deaths in ovarian cancer. The overall survival (OS) of HGSOC is poor and still remains a clinical challenge. High-grade serous ovarian cancer can be divided into 4 molecular subtypes. The prognosis of different molecular subtypes is still unclear. We aimed to investigate the prognostic values of immunohistochemistry-based different molecular subtypes in patients with HGSOC. Methods We analyzed the protein expression of representative biomarkers (CXCL11, HMGA2, and MUC16) of 3 different molecular subtypes in 110 formalin-fixed, paraffin-embedded HGSOC by tissue microarrays. Results High CXCL11 expression predicted worse OS, not disease-free survival (DFS; P = 0.028 for OS, P = 0.191 for DFS). High HMGA2 expression predicted worse OS and DFS (P = 0.037 for OS, P = 0.021 for DFS). MUC16 expression was not associated with OS or DFS (P = 0.919 for OS, P = 0.517 for DFS). Multivariate regression analysis showed that CXCL11 combined with HMGA2 signature was an independent predictor for OS and DFS in patients with HGSOC. Conclusions CXCL11 combined with HMGA2 signature was a clinically applicable prognostic model that could precisely predict an HGSOC patient's OS and tumor recurrence. This model could serve as an important tool for risk assessment of HGSOC prognosis.
Objectives: The aim of this study was to investigate the different efficacies of various fertility-preserving therapies for grade 1 presumed stage IA endometrial cancer. Methods: We searched the major online databases (PubMed, MEDLINE, Cochrane Library, Web of Science, and Ovid) and retrieved all the research on fertility-preserving treatment for young, grade 1 presumed stage IA endometrial adenocarcinoma patients since January 2000. We used the systemic evaluation of the Cochrane Collaboration to select the literature and merge the data we collected using R3.2.2 software (R Development Core Team, Auckland, New Zealand). By comparing the remission, recurrence, and pregnancy rates, we evaluated the efficiency of 3 existing fertility-preserving treatments indirectly: a) taking oral progestin only therapy, b) hysteroscopic resection followed by progestin therapy, and c) intrauterine progestin therapy: levonorgestrel-releasing intrauterine system combined with gonadotropin-releasing hormone agonist/progestin therapy. Results: Twenty-eight studies met the selection criteria. A total of 619 cases were included in this study. The group that took oral progestin only (456 patients) achieved a complete remission rate (CRR), recurrence rate (ReR), and pregnancy rate (PregR) of 76.3%, (95% confidence interval [CI], 70.7%-81.1%); 30.7% (95% CI, 21.0%-42.4%); and 52.1% (95% CI, 41.2% Y66.0%), respectively. The hysteroscopic resection followed by progestin therapy group (73 patients) achieved a CRR, ReR, and PregR of 95.3% (95% CI, 87.8%-100%); 14.1% (95% CI, 7.1%-26.1%); and 47.8% (95% CI, 33.0%-69.5%), respectively. The intrauterine progestin therapy group (90 patients) achieved aCRR, ReR, and PregRof 72.9% (95% CI, 60.4%-82.5%); 11.0% (95% CI, 5.1%-22.0%); and 56.0% (95% CI, 37.3%-73.1%), respectively. Conclusions: The existing results show that patients who received hysteroscopic resection followed by progestin therapy achieved the highest CRR. Patients who received oral progestin only might bemore likely to recur and havemore systemic adverse effects. Recent intrauterine progestin therapy such as levonorgestrel-releasing intrauterine system combined with gonadotropin-release hormone receptor agonist/progestin have a satisfactory PregR and low ReR rate. Considering the inherent limitations of the studies we included, further welldesigned, randomized controlled trials are necessary to confirm and update this analysis.
Objective: Ovarian cancer (OC) is one of the lethal gynecological malignancies. Most women affected by OC with malignant ascites will relapse. Peptidomics, as an emerging branch of proteomics, is more applied in screening of disease biomarkers, diagnosis, treatment, and monitoring. However, there is still little in-depth analysis about peptidomics study in OC with malignant ascites. Methods: A comparative peptidomic profiling of ascites fluid between 6 OC patients and 6 benign gynecological conditions using liquid chromatography-tandem mass spectrometry was analyzed. Afterward, the Ingenuity Pathway Analysis was performed to reveal the potential function of peptide-protein precursors. Results: A total of 4388 nonredundant peptides were identified, 104 of which were significantly differentially expressed in the ascites fluid of OC and benign gynecological conditions (>2-fold changes and P < 0.05): 52 peptides were upregulated while 52 peptides were downregulated. These peptides were imported into the Ingenuity Pathway Analysis and identified putative roles in OC. Conclusions: We identified the peptidome patterns of patients with OC and benign gynecological conditions, and these differentially expressed that peptides might play an important role during occurrence and development of OC and will be in hope to explore bioactive peptides in the pathogenesis of OC.
Objective: Ovarian cancer (OC) is the second most lethal gynecological cancer among women throughout the world. Protocadherin-8 (PCDH8) could function as a candidate tumor suppressor. However, the link between PCDH8 and OC development is poorly understood. Materials and Methods: A total of 68 OC patients were retrospectively enrolled. Clinical information was collected and cancer tissues were used for tissue microarray. The PCDH8 expression was determined on tissue microarray by immunohistochemical staining, and PCDH8 protein was detected in cancer tissues and adjacent tissue by western blotting. Human OC cell lines (SKOV-3 and OVCAR-3) were used to assess the effects of PCDH8 overexpression by western blot and real-time PCR analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, wound healing migration assay, colony formation assay and invasion assays were performed to assess the influence of PCDH8 on cell function. Cells with Luc-nonspecific Lentiviral or Luc-Lentiviral with PCDH8 gene were subcutaneously injected into nude mice to observe the effect of PCDH8 gene on tumor growth. Bioluminescence imaging was used to observe tumor volume. Results: We found a low expression of PCDH8 in OC tissues versus the corresponding adjacent tissue. The PCDH8 expression, International Federation of Gynecology and Obstetrics stage, metastasis and recurrence were the independent prognostic factors for over-all survival by multivariate analyses. Furthermore, the patients with recurrence presented a low level of PCDH8 in OC tissues, and patients with advanced tumor stage also had a low PCDH8 expression. Importantly, the low expression of PCDH8 in OC tissues had a poor prognosis with a low overall survival rate. Overexpression of PCDH8 could inhibit OC cell growth/proliferation, migration, invasion, and colony formation in vitro. In vivo experiments also proved that overexpression of PCDH8 could inhibit OC cell growth/proliferation. Conclusions: Protocadherin-8 might be considered as a candidate tumor suppressor and play a crucial role in the progression of OC.
Objective: This study aimed to investigate whether platelet-derived growth factor D (PDGF-D) is a prognostic biomarker and is associated with platinum resistance in epithelial ovarian cancer, which has not been studied by others previously. Methods: In this study, we detected expression of PDGF-D in ovarian cancer tissues through immunohistochemistry and Western blotting. Furthermore, we analyzed the association between PDGF-D expression and clinicopathological features including prognosis in epithelial ovarian cancer. Statistical analyses were performed by using (2) test, log-rank test, Cox regression test, and Kaplan-Meier method. Results: High PDGF-D expression is positively correlated with International Federation of Gynecology and Obstetrics stage (P < 0.001), histologic grade (P < 0.001), lymph node metastasis (P = 0.022), and poor prognosis (P < 0.001). Platelet-derived growth factor D in platinum-resistant cases is overexpressed compared with that in platinum-sensitive cases (P < 0.001). Obstetrics stage (P = 0.029) and PDGF-D overexpression (P < 0.001) are independently correlated with platinum resistance. Conclusions: Our study indicates that PDGF-D overexpression is an independent predictor of platinum-based chemotherapy resistance and that it may also be a potential biomarker for targeted therapy and poor prognosis.
Aim: This study was aimed to evaluate the risk factors of recurrence and the value of nodal involvement in patients with serous borderline ovarian tumors (SBOT). Methods: Two hundred twenty-five patients who underwent surgery and were diagnosed with SBOT were retrospectively studied. Univariate and multivariate analyses were used to assess the risk factors for recurrence. Patients' clinical pathologic characteristics were compared between the patients who presented lymph node involvement and those who did not. The significant values of lymph condition influencing 5-year disease-free survival were also evaluated by statistical analysis. Results: Both univariate and multivariate analyses showed that risk factors for recurrence were micropapillary (P = 0.021), fertility-preserving surgery (P = 0.014), and laparoscopic approach (P = 0.009). Of these 112 patients on whom lymphadenectomy was performed, 17 cases showed lymph node positive, whereas the remaining 95 patients did not. Significant differences in terms of lymph node numbers (P < 0.0001), invasive implant (P = 0.022), and International Federation of Gynecology and Obstetrics staging (P < 0.0001) were observed between the 2 groups of lymphatic node involved or not. Kaplan-Meier curves of 5-year disease-free survival revealed that there were no significant differences either between groups of lymphatic node involved or not (P = 0.778) and groups of removed nodes whether more than 10 or not (P = 0.549). Conclusions: Micropapillary, fertility-preserving, and laparoscopic approach were factors significantly affecting the recurrence of SBOT by both univariate and multivariate analysis. Lymph node metastasis did not seem to be correlated to a worse prognosis of SBOT.
Objective: We investigated the short-term outcomes and pregnancy rate after a laparoscopic approach to fertility preservation in patients with borderline ovarian tumors (BOTs). Methods: Clinic-pathologic variants of patients with BOTs who underwent conservative surgery at the Tianjin Central Hospital of Obstetrics and Gynecology between January 2009 and July 2015 were retrospectively analyzed. Results: Among 211 patients with BOTs, 74 (35.1%) received conservative surgery (44 cases using a laparoscopic approach and 30 cases using a laparotomy approach). The mean age of the laparotomy group was significantly younger than that of the laparoscopic group (P = 0.024). The maximal longitude of the tumor in the laparotomy group was significantly longer than that in the laparoscopic group (P < 0.001). The number of incomplete surgery cases in the laparoscopic group was significantly greater than that in the laparotomy group (P < 0.001). The 2 groups showed no significant differences in gravidity and parity before surgery, abnormality of serum tumor makers, tumor lateralities, ascites, histology, duration of follow-up, pregnancy rate after surgery, or postoperative recurrence. Total recurrent rate was 6.7% (5/74). Two cases in laparotomy group and 3 cases in laparoscopic group relapsed respectively. There was no significant difference of recurrent rate between the 2 groups. The total pregnant rate was 33.8% (25/74). Nine patients (30%) in the laparotomy group and 16 patients (36.4%) in the laparoscopic group became pregnant during follow-up respectively. There were no significant differences in the postoperative durations of pregnancy, pregnancy type, age at pregnancy, tumor lateralities, ascites, or type of pathology between 2 groups. The pregnancy rate of incomplete surgery cases in laparoscopic group was significantly higher than that of laparotomy group (P = 0.011). No recurrence occurred among the pregnant cases. Conclusions: A comprehensive laparoscopic surgery was not performed in incomplete surgery patients undergoing complete exploration. Good short-term outcomes and pregnancy were observed in patients receiving conservative laparoscopic surgery for BOTs, especially in patients receiving incomplete conservative laparoscopic surgery.
Objective Ovarian cancer is a common gynecological cancer, and parity is negatively associated with the incidence of this disease. This negative association is hypothesized to be due in part to shifting the balance of estrogen and progesterone toward more progesterone and reduced ovulation during pregnancy. However, studies suggested that parity is also associated with estrogen-independent gynecological cancers suggesting balance of hormones may not be the only protective factor. Extracellular vesicles (EVs) play an important role in cell-to-cell communication in physiological and pathological conditions. During pregnancy, large amounts of EVs are extruded from the placenta, and they seem to be involved in the remarkable adaptation of a woman's body to normal pregnancy. We hypothesized that EVs extruded from the placenta play a role in this protective effect. Methods Placental EVs were collected from first-trimester placentae, and cancer cell EVs were isolated from ovarian cancer cells. The EVs were exposed to ovarian cancer cells for 48 hours. The proliferation of cancer cells and the cell cycle were measured. In addition, phagocytosis of deported placental EVs by cancer cells was also measured. Results The proliferation of cancer cells was significantly reduced by treatment with placental EVs (P = 0.001, analysis of variance), but not EVs from monocytes (P = 0.195), compared with untreated cancer cells. Furthermore, placental EVs also prevented the proliferation of cancer cells induced by cancer cell-derived EVs (P = 0.001). This inhibition of proliferation of ovarian cancer cells was partially due to phagocytosis of placental EVs by cancer cells. Phagocytosis of placental EVs delayed progression through the cell cycle. Calreticulin, a phagocytic eat me signal carried by placental EVs significantly inhibited ovarian cancer growth (P = 0.001). Conclusions Our data demonstrated that EVs extruded from the placenta prevented ovarian cancer cell growth by a mechanism that involved delaying progression of the cell cycle after phagocytosis of the EVs.
Although calcification in the gynecologic tumor microenvironments is a common phenomenon, doctors and researchers still disregard or ignore the issue. In fact, this change in the gynecologic tumor microenvironments is clinically significant and a number of studies have reported an association between calcification and gynecological tumor progression. In ovarian cancer, calcification is predominantly psammomatous and largely occurs in serous papillary ovarian tumors. In addition, calcification in ovarian cancer correlated with lower histologic grade and may indicate a poorer survival rate. In uterine fibroids, calcification occurs as a degenerative change and is predictive of a good prognosis. As for endometrial cancer and cervical cancer, calcification rarely occurs in these cancers. The mechanism of calcification in the gynecologic tumor microenvironments is not currently clear. One theory is that calcification occurs due to degeneration of the tumor cells; another theory is that calcification occurs in response to secretions from cells in the tumor microenvironment. Although previous studies have revealed a direct association between calcifications and gynecological tumors, this association has not been fully clarified. To better clarify the significance of calcification in terms of diagnosing and treating gynecological tumors, the associations between calcification and the different histologic stages and prognosis in gynecological tumors should be further studied. In particular, more attention should be paid to the morphological characteristics, chemical nature, and mechanism of calcifications in the gynecological tumor microenvironments.
Objective This study aimed to investigate the role of neoadjuvant bleomycin, etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk sac tumors (YSTs). Methods Between July 1982 and December 2015, a total of 58 patients with YST were initially treated at our institution, among which 18 were evaluated to be inoperable and received neoadjuvant BEP regimen. They were either too debilitated by the disease [Eastern Cooperative Oncology Group Performance Status Scale (ECOG ps) 2] to undergo a major surgery or were with too extensively disseminated lesions to be optimally debulked. This cohort of patients was retrospectively reviewed. Results One or 2 cycles of BEP regimen were prescribed to the majority of patients preoperatively. At the completion of neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%) exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16 (88.9%) had nearly complete pathological regression. Seventeen patients were cytoreduced to no macroscopic residual disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm or less. No major surgical complications occurred. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year disease-free survival and overall survival were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with the desire to preserve their fertility, and 5 infants were delivered in 6 patients who attempted conception. Conclusions One or 2 cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a chance for cure in extensively advanced patients with YSTs and help pave the way for fertility-sparing surgery.
Purpose The aim of this study was to evaluate the efficacy of using nedaplatin to replace cisplatin for concurrent chemoradiotherapy (CCRT) in patients with newly diagnosed locally advanced cervical cancer. Methods The medical records of 155 patients with cervical cancer who had undergone CCRT with cisplatin (n = 85) or nedaplatin (n = 70) between January 2012 and January 2017 were retrospectively reviewed. Propensity score analysis with 1:1 matching with the nearest neighbor matching method was performed to assess response rates, progression-free survival, overall survival, and toxicity between 2 groups. Results Propensity score matching identified 63 patients in each group. After matching, compared with patients treated with cisplatin-based concurrent chemoradiotherapy (CisRT), we found that patients treated with nedaplatin-based concurrent chemoradiotherapy (NedaRT) had a significant higher recurrence rate (25.4% vs 42.9%; P = 0.04). In addition, the 3-year progression-free survival rate for NedaRT group was also worse than that for the CisRT group (52.2% vs 63.4%, P = 0.03). There was no difference in the overall response rates between the CisRT and NedaRT groups (87.3% and 90.5%, respectively; P = 0.57). The rates of 3-year overall survival and grades 3 to 4 toxicities were similar between the 2 groups. Conclusions The clinical outcome of this cohort of patients with locally advanced cervical cancer treated with CCRT did in no way provide support for the use of nedaplatin in place of cisplatin in chemoradiation and demonstrated no equivalence of the 2 drugs. Cautions should be taken for the replacement among platinum complexes in cancer treatment.
Background Angiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer. Methods We searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events. Results Fifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71-0.97) and no improved OS (HR, 0.95; 95% CI, 0.86-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65-0.81) and OS (HR, 0.84; 95%CI, 0.74-0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52-0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79-0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63-1.01) or OS (HR, 1.06; 95% CI, 0.88-1.28) in the pure maintenance therapy. In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66-3.97), hypertension (RR, 7.60; 95% CI, 2.79-20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34-3.84), proteinuria (RR, 4.31; 95% CI, 2.15-8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12-2.63). Conclusions Combination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.
Objective This review aimed to update the research and development of cellular senescence in the treatment of ovarian cancer. We discussed the current mechanisms of senescence and the major biomarkers of senescence, especially the methods of cellular senescence in the treatment of ovarian cancer. Materials and Methods We collected all relevant studies in PubMed from 1995 to 2017. The search terms included senescence and cancer, senescence and ovarian cancer, senescence-associated secretory phenotype, ovarian cancer and chemotherapy, radiotherapy, or biotherapy. PubMed search with the key words senescence and ovarian cancer lists approximately 85 publications. After excluding the duplicated articles, we selected 68 articles most relevant to senescence and ovarian cancer in this review. Results Cellular senescence plays a key role in various biological processes of ovarian cancer, which is closely related with the occurrence, development, and treatment of ovarian cancer. Cellular senescence on the one hand can reduce the dose of chemotherapy in ovarian cancer; on the other hand, it also can solve the problem of tumor resistance to apoptosis. Therefore, cellular senescence has been shown to be the third intracellular mechanism of ovarian cancer prevention followed by cellular DNA repair and apoptosis. Conclusions In the near future, cellular senescence therapy could be a powerful tool for ovarian cancer treatment.
Background The prognostic factors of uterine serous carcinoma (USC) vary among studies, and there is no report of Chinese USC patients. Objective The aim of this study was to investigate the clinicopathological characteristics and prognostic factors in Chinese patients with USC. Methods Patients with USC from 13 authoritative university hospitals in China and treated between 2004 and 2014 were retrospectively reviewed. Three-year disease-free survival rate (DFSR), cumulative recurrence, and cumulative mortality were estimated by Kaplan-Meier analyses and log-rank tests. Multivariate Cox regression analysis was used to model the association of potential prognostic factors with clinical outcomes. Results Data of a total of 241 patients were reviewed. The median follow-up was 26 months (range, 1-128 months). Median age was 60 years (range, 39-84 years), and 58.0% had stages I-II disease. The 3-year DFSR and cumulative recurrence were 46.8% and 27.7%. Advanced stage (III and IV) (P = 0.004), myometrial invasion (P = 0.001), adnexal involvement (P < 0.001), lymph node metastasis (P = 0.025), and positive peritoneal cytology (P = 0.007) were independently associated with 3-year DFSR. Advanced stage (P = 0.017), myometrial invasion (P = 0.008), adnexal involvement (odds ratio, 2.987; P = 0.001), lymph node metastasis (P = 0.031), and positive peritoneal cytology (P = 0.001) were independently associated with the cumulative recurrence. Myometrial invasion (P = 0.004) and positive peritoneal cytology (P = 0.025) were independently associated with 3-year cumulative mortality. Conclusions Peritoneal cytology and myometrial invasion could be independent prognostic factors for 3-year DFSR, cumulative recurrence, and cumulative mortality of patients with USC. Prospective studies are needed to confirm these results.