Journal of Gynecologic Oncology最新文献

Objective: Uterine corpus endometrial carcinoma (UCEC) is a common gynecologic malignancy with poor prognosis in advanced stages. Circular RNA (circRNA) and exosomes have been documented as significant contributors to the advancement of tumor cells, but the specific regulatory mechanisms between them is unclear. Therefore, our study attempts to explore the mechanism between them.

Methods: Firstly, we isolated and identified exosomes, and then validated their role in UCEC progression by experiments in vivo and in vitro. Secondly, a human competing endogenous RNA (ceRNA) array was used to identify the circRNA with the most significant differences in expression from serum of UCEC patient, and validated its role in UCEC progression by experiments in vitro. Then, we find the target gene of this circRNA by RNA sequencing, and further clarify the correlation between the 2 and their role in tumor cell progression through experiments in vitro.

Results: Serum exosomes in patients with UCEC can promote the progression of UCEC. The human ceRNA array identified that circRNA 0002577 (circ_0002577) was up-regulated and was the most significantly altered circRNA. Moreover, the up-regulated circ_0002577 in exosomes derived from UCEC patients promote proliferation and migration of UCEC. Based on RNA sequencing results, general transcription factor II-I repeat domain-containing 1 (GTF2IRD1) gene was identified as being highly correlated with circ_0002577. Additionally, a positive correlation between circ_0002577 and GTF2IRD1 was confirmed by experiments in vitro.

Conclusion: Exosomes promote UCEC progression through circ_0002577 mediated regulation of GTF2IRD1, highlighting the potential therapeutic targets in treatment for UCEC.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) represent predominant histological subtypes of cervical cancer. To improve screening efficacy, we leveraged RNA sequencing data from 4 cervical SCC samples, 4 cervical ADC samples, and 8 normal cervix samples and conducted a comprehensive mRNA and long noncoding RNA (lncRNA) profiling analysis followed with a multi-phase study comprising 556 samples. Validating the RNA sequencing data in a clinical sample set comprising 45 normal cervix tissues, 45 SCC tissues, and 45 ADC tissues, we identified 9 mRNAs (SMC1B, OTX1, GRP, CELSR3, HOXC6, ITGB6, WDR62, SEPT3, and KLHL34) and 4 lncRNAs (FEZF1-AS1, LINC01305, LINC00857, and LINC00673) differentially expressed in both SCC and ADC samples. Utilizing quantitative reverse transcription polymerase chain reaction analysis and receiver operating characteristic (ROC) curve analysis in a training set (45 normal, 126 SCC, and 82 ADC tissues), we refined a novel mRNA-lncRNA-based panel (SMC1B/CELSR3/FEZF1-AS1/LINC01305). Employing logistic regression model and ROC analysis, this panel exhibited significant distinctions and promising area under the curve (AUC) values in both SCC (AUC=0.9520, p<0.0001) and ADC (AUC=0.9748, p<0.0001) tissues. Subsequent validation in an independent set (11 normal, 32 SCC, and 20 ADC tissues) demonstrated its diagnostic accuracy in both SCC (AUC=0.9659, p<0.0001) and ADC (AUC=0.9636, p<0.0001) patients. Notably, this tissue-based biomarker panel robustly discriminated precancerous lesion and cervical cancer patients from non-disease controls in a blood-based validation set (30 normal, 25 HSIL and 50 cervical cancer) with an AUC value of 0.9320. This study presents a non-invasive, efficient diagnostic panel for cervical cancer screening.

Objective: Hepatic metastasectomy for gynecologic cancers remains controversial. Management of advanced endometrial cancer (EC) is complex. The purpose of this study is to analyze the efficacy of liver metastasectomy (LM) in the treatment of metastatic EC.

Methods: The National Cancer Database was used to create a retrospective cohort of adult women with EC metastatic to the liver between 2010 and 2016. Overall survival and all-cause mortality were estimated with inverse probability of treatment weighting (IPTW) curves and IPTW Cox proportional hazard regression, respectively.

Results: Among 999 EC patients with oligometastatic disease to the liver, 162 (16.2%) underwent LM, 614 (61.5%) received chemotherapy, and 129 (12.9%) had chemotherapy and LM. Those who underwent chemotherapy, 1-, 2-, and 3-year survival for chemotherapy + LM versus chemotherapy alone were 67.8 versus 56.5%, 44.9 versus 33.4%, and 35.1 versus 23.1%, respectively. In unadjusted analysis, chemotherapy + LM group had reduced mortality risk (hazard ratio [HR]=0.68; 95% confidence interval [CI]=0.54-0.86) with longer median survival time (20.1 vs. 14.6 months, p=0.011) compared to chemotherapy alone. Adjusting for demographics and treatment characteristics, a possible reduction in mortality was associated with chemotherapy + LM (HR=0.74; 95% CI=0.55-1.01) compared to chemotherapy alone.

Conclusion: This study of LM for EC suggests LM in addition to chemotherapy may be associated with improved outcomes for patients with EC.

Objective: This study aimed to evaluate and compare recurrence-free survival (RFS) between radical hysterectomy followed by adjuvant chemotherapy and initial chemoradiotherapy for cervical cancer at our institution.

Methods: In this retrospective study, we enrolled patients diagnosed with stage IB2-IIB cervical cancer according to the International Federation of Gynecology and Obstetrics 2018 staging system, who underwent either radical hysterectomy with pelvic lymphadenectomy followed by adjuvant chemotherapy or initial concurrent chemoradiation at our institution between 2009 and 2022.

Results: Among these patients, 74 and 110 underwent radical hysterectomy and chemoradiation, respectively. The radical hysterectomy group exhibited significantly improved RFS compared with the chemoradiation group; however, no significant difference was observed in overall survival between the groups. Cox hazard analysis for RFS showed that, among the clinical risk factors identified before the initial treatment, only parametrial invasion was statistically significant. No significant difference in RFS was observed between the radical hysterectomy group and chemoradiation group. Regarding recurrence patterns, para-aortic lymph node recurrence occurred significantly more frequently in the chemoradiation group than in the radical hysterectomy group. Postoperative ureteral injury was reported in once case and postoperative ureteral stenosis in 2 cases in the radical hysterectomy group. In contrast, vesicovaginal fistula and rectovaginal fistula were reported in one case each in the chemoradiation group.

Conclusion: Radical hysterectomy followed by adjuvant chemotherapy provided RFS outcomes comparable to those achieved with initial chemoradiotherapy for stage IB2-IIB and IIIC1-2 cervical cancer. These findings suggest that both approaches are viable, although further prospective studies are needed.

Objective: In the background of endometrial hyperplasia triggered by obesity and estrogen, could the perilipin 2 (PLIN2) serve as a possible prognostic marker for early atypical endometrial hyperplasia (AEH)?

Methods: A retrospective study examined blood lipid levels in endometrial cancer (EC) or AEH patients. An AEH mice model was established administrating with estradiol and/or high-fat (HF) diet. Hematoxylin and eosin staining were employed to assess pathological changes in the endometrium. Immunohistochemical staining were employed to evaluate the expression of adipose metabolism and endometrial hyperplasia proteins. The Cell Counting Kit-8 assay, cell colony-forming assays, and western blotting were utilized to verify the impact of oleic acid (OA) on HEC-1A cells.

Results: The retrospective study revealed elevated blood lipid levels among patients with EC or AEH. Prolonged HF diet stimulated the endometrium to exhibit features of complex atypical hyperplasia. In the early stage, PLIN2 (p=0.006) expression significantly increased with endometrial glandular hyperplasia. Both PLIN2 (p=0.008) and progesterone receptor (PR; p=0.019) exhibited elevated expression concurrent with simple endometrial hyperplasia. When AEH occurred, there were notable rise in the expression of PLIN2 (p<0.001), PR (p=0.044), and estrogen receptor (p=0.045). The atypical hyperplasia glands demonstrated notably elevated PLIN2 expression in comparison to surrounding normal glands in AEH lesions. OA was found to enhance the proliferation and clonal formation of HEC-1A cells. HEC-1A cells induced by OA demonstrated elevated autophagy levels accompanied by enhanced expression of PLIN2.

Conclusion: PLIN2 may potentially serve as a biomarker for early development of AEH and EC, facilitating diagnosis and intervention and contributing to the determination of prognosis.

Objective: To investigate the incidence and risk factors of cardiovascular disease (CVD) in adolescent and young adult survivors of cervical cancer.

Methods: This retrospective cohort study used data from the Korean National Health Insurance Service. Adolescent and young adult (AYA) cervical cancer survivors (n=7,803) were matched with non-cancer controls (n=23,327) using 1:3 propensity score matching, and hazard ratios (HRs) for CVD were determined using Cox regression models. Multivariable Cox regressions were used to assess CVD incidence according to cancer treatment and identify risk factors.

Results: A total of 7,803 AYA survivors with cervical cancer were analyzed in this study during a median 8.9 years of follow-up. They developed any CVD with an adjusted HR of 1.47 (95% confidence interval [CI]=1.33-1.62) compared with the non-cancer controls. Those who underwent concurrent chemoradiotherapy had markedly elevated risks of heart failure (subHR=2.66; 95% CI=1.24-5.72), ischemic heart disease (subHR=1.78, 95% CI=1.11-2.86), deep vein thrombosis (subHR=15.32; 95% CI=9.16-25.63), and pulmonary embolism (subHR=14.99; 95% CI=6.31-35.62). Diabetes, hypertension and chemoradiation therapy were identified as potential risk factors that increase the risk of CVD by 1.55-fold, 1.62-fold and 2.64-fold, respectively.

Conclusion: These findings indicate a need to pay increased attention to cardiovascular health management in adolescent and young adult cervical cancer survivors, particularly those treated with chemoradiotherapy.

Objective: Cervical cancer rates in Japan (16.0/100,000) exceed the global average rate (11.3/100,000, according to the High/Very-High Human Development Index in 2020). This necessitates the evaluation of care quality and the quality indicators (QIs) for cervical cancer that were developed in 2013 to serve this purpose. This study updated these indicators using current evidence and consensus while longitudinally examining trends in practice patterns.

Methods: The revision involved reviewing existing QIs and patterns of care indicators and incorporating new indicators using the modified Delphi method. Adherence to these indicators was assessed using a linked hospital-based cancer registry-based diagnostic procedure combination database covering approximately 70% of patients with cancer in Japan. The longitudinal trends of the existing indicators were evaluated using the linear probability model.

Results: Seven new indicators were added to the existing twelve. Two of the new indicators mainly focused on early-stage surgical intervention, while one focused on advanced-stage bevacizumab combination therapy, with adherence rates of 81.7%, 0.8%, and 45.9%. Longitudinal analyses revealed significant improvements with the use of cisplatin in concurrent chemoradiotherapy for advanced-stage cervical cancer (+1%/year), oral anticancer agents as maintenance therapy after primary treatment for early-stage cervical cancer (-0.8%/year), and hysterectomy for adenocarcinoma in situ in patients above 44 years old (-2%/year).

Conclusion: The QIs for cervical cancer in Japan have been revised based on 2022 evidence. The existing and new indicators should be continually evaluated to correspond to the latest knowledge. This will facilitate the standardization and promotion of bottom-up improvements in cervical cancer care.

Objective: Gynecological cancer treatments, including radiotherapy (RT) and chemotherapy, leads to various bladder complications. The anatomical proximity of the treatment site to the urinary bladder primarily explains the complications following RT, while chemotherapy contribute to bladder dysfunction through systemic mechanisms. This study systematically reviews the nature, extent, and prevalence of bladder complications among women treated for these malignancies, underscoring the influence of treatment modalities on bladder function.

Methods: A comprehensive search of databases including Embase, Scopus, PubMed/MEDLINE, CINAHL, and the Cochrane Library was conducted, focusing on women undergoing RT, chemotherapy, or both for gynecological cancers. Meta-regression was performed to quantify the effects of treatments on bladder function, using random-effect models.

Results: From 15,081 citations, 12 studies with a total of 12,469 participants were included. Our analysis revealed a broad spectrum of bladder complications, with urinary incontinence (UI) and overactive bladder symptoms being common, alongside with radiation cystitis and anatomical defects formation. The prevalence of these complications varied, reflecting the complexity of treatment modalities, cancer types, and patient characteristics. Specifically, UI rates ranged from 2.6% to 84%, while the incidence of fistula formation and ureteral stenosis remained relatively low but clinically significant. Urodynamic findings showed reduced bladder capacity and increased detrusor overactivity in up to 44% of evaluated patients, highlighting treatment's impact on bladder function.

Conclusion: Bladder complications are prevalent among gynecological cancer survivors, with notable occurrences associated with chemotherapy and RT treatments. Integrated care focusing on both oncological and urological health is essential for enhancing survivors' quality of life.

Trial registration: PROSPERO Identifier: CRD42023467123.

Objective: With the development of novel antibody-drug conjugates (ADCs), folate receptor alpha (FOLR1) is a promising therapeutic target for the treatment of platinum-resistant tubo-ovarian carcinomas. The main aims of this study were to assess FOLR1 protein expression in a large cohort of ovarian carcinoma histotypes. To inform future clinical trial design we identified molecular correlates of FOLR1 expression in low-grade serous carcinoma (LGSC).

Methods: One thousand five hundred forty-seven ovarian carcinoma samples from 5 different Canadian cohorts were successfully evaluated by immunohistochemistry for FOLR1 expression using the PS2+ system. Statistical analyses with clinicopathological parameters, LGSC molecular subtypes, and overall survival (OS) were performed.

Results: High FOLR1 expression was detected in 44% of high-grade serous carcinomas, and in 30% LGSC, 8% clear cell, 6% endometrioid, and 0% mucinous and/or mesonephric-type adenocarcinomas. In 160 LGSC cases, FOLR1 expression was more frequent in cases with normal MAPK pathway status (37% MAPK wild type vs. 14% canonical MAPK pathway mutations; p=0.002), low progesterone receptor (PR) expression (41%) vs. 23% (Allred score >2; p=0.02), and p16 loss (48% p16 absent vs. 26% normal; p=0.03). Canonical MAPK mutation status and PR expression remained significant on multivariable analysis. No significant associations between OS and FOLR1 expression were observed.

Conclusion: A significant proportion of LGSC express high FOLR1 levels supporting the development of clinical trials to investigate ADCs targeting FOLR1 as novel agents for treating this disease. In LGSC, high FOLR1 expression was associated with fewer MAPK pathway alterations, low PR expression, and p16 loss.