Circulating tumor DNA: a noninvasive biomarker for tracking ovarian cancer

Ovarian cancer is the fifth leading cause of cancer-related mortality in women worldwide. Despite the development of technologies over decades to improve the diagnosis and treatment of patients with ovarian cancer, the survival rate remains dismal, mainly because most patients are diagnosed at a late stage. Traditional treatment methods and biomarkers such as cancer antigen-125 as a cancer screening tool lack specificity and cannot offer personalized combinatorial therapy schemes. Circulating tumor DNA (ctDNA) is a promising biomarker for ovarian cancer and can be detected using a noninvasive liquid biopsy. A wide variety of ctDNA applications are being elucidated in multiple studies for tracking ovarian carcinoma during diagnostic and prognostic evaluations of patients and are being integrated into clinical trials to evaluate the disease. Furthermore, ctDNA analysis may be used in combination with multiple “omic” techniques to analyze proteins, epigenetics, RNA, nucleosomes, exosomes, and associated immune markers to promote early detection. However, several technical and biological hurdles impede the application of ctDNA analysis. Certain intrinsic features of ctDNA that may enhance its utility as a biomarker are problematic for its detection, including ctDNA lengths, copy number variations, and methylation. Before the development of ctDNA assays for integration in the clinic, such issues are required to be resolved since these assays have substantial potential as a test for cancer screening. This review focuses on studies concerning the potential clinical applications of ctDNA in ovarian cancer diagnosis and discusses our perspective on the clinical research aimed to treat this daunting form of cancer.

Levels of endoplasmic reticulum stress-related mRNA in peritoneal fluid of patients with endometriosis or gynaecological cancer

Objective To compare the levels of endoplasmic reticulum (ER) stress-associated mRNAs and the clinical characteristics of patients with endometriosis or gynaecological cancer. Methods This prospective study obtained intraperitoneal fluid samples from female patients that underwent surgery. The levels of ER stress mRNAs in the peritoneal fluid, including C/EBP-homologous protein (CHOP), X-box binding protein 1 (sXBP1), activating transcription factor 6 (ATF6), immunoglobulin heavy chain-binding protein (BiP), inositol-requiring enzyme 1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), were measured using real-time reverse transcription–polymerase chain reaction in patients with benign disease without endometriosis (control group), with endometriosis or with gynaecological cancer. Results This study enrolled 126 patients: 46 control patients; 47 with endometriosis; and 33 with cancer. The levels of CHOP and BiP mRNA were significantly higher in the control group compared with the cancer group. Levels of sXBP1 and ATF6 mRNA were significantly higher in the cancer group than in the control and endometriosis groups. In the endometriosis group, ATF6 mRNA level was inversely correlated with age and positively correlated with serum cancer antigen 125 levels; and ATF6 and PERK mRNA levels were inversely correlated with parity. Conclusion The levels of ER stress-related mRNAs were related to the pathogenesis of endometriosis and gynaecological cancers.

Serum HE4 and CA125 combined to predict and monitor recurrence of type II endometrial carcinoma

There is no recognized serum biomarker to predict the recurrence of endometrial carcinoma (EC). We aimed to explore serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) as the biomarkers to predict and monitor recurrence of type II EC. 191 patients diagnosed with type II EC were involved for this retrospective study. Comparing recurrent with non-recurrent patients, HE4 levels resulted a statistically significant difference at primary diagnosis and recurrence, respectively (P = 0.002 and P = < 0.001), while CA125 levels resulted statistically significant (P = < 0.001) at recurrence. According to receiver operating characteristic curve analysis, the areas under the curve were significant for HE4 levels at primary diagnosis and recurrence predicting recurrence. Furthermore, CA125 levels at recurrence were significant. And the combination of both markers showed the higher sensitivity and specificity than single one. Patients with higher HE4 levels were associated with worse disease-free survival and overall survival, the opposite was true for patients with lower HE4 levels. The preoperative HE4 levels could be used to evaluate the risk factors of type II EC. Which suggested that HE4 levels might associated with the prognosis of type II EC. And combination of HE4 and CA125 could be applied to monitor recurrence during follow-up.

Prognostic Value of CEA, CA19-9, CA125, CA724, and CA242 in Serum and Ascites in Pseudomyxoma Peritonei

PurposeTo investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA19-9, CA724, and CA242 in serum and ascites of pseudomyxoma peritonei (PMP) patients and evaluate the predictive value of these elevated biomarkers in pathological grade, completeness of cytoreduction (CC), and survival.MethodsFrom May 2009 to October 2019, a total of 512 patients diagnosed with PMP through pathology in Aerospace Center Hospital were enrolled. The serum and ascites tumor biomarkers were obtained. The diagnostic values between serum and ascites biomarkers in pathology and CC were compared by the receiver operating characteristic (ROC) curves. The correlation between pathology, cytoreduction, and biomarkers was calculated by univariate and multivariate logistic regression. The associations between different numbers of elevated biomarkers and survival status were examined using univariate and multivariate backward Cox proportional hazard regression models.ResultsThe results showed that the areas under the ROC curves (AUROC) in the diagnosis of CC were 0.798 (95% CI: 0.760–0.836) and 0.632 (95% CI: 0.588–0.676) in serum and ascites biomarkers, respectively. The elevated serum and ascites biomarkers were independent risk factors for both pathology and CC. The 1-year, 3-year, and 5-year survival rates were 89.07%, 73.22%, and 66.94%, respectively. Longer survival was observed in patients who had less than two elevated serum biomarkers compared with those with 2–3 and 4-5 elevated serum biomarkers (p &lt; 0.001).ConclusionCEA, CA125, CA19-9, CA724, and CA242 in serum and ascites can be used to judge the severity and predict the resectability. Furthermore, different numbers of elevated biomarkers can help determine the prognosis of PMP.

Case Report About Extraperitoneal Metastasis of Cervical Adenocarcinoma In Situ

Background: adenocarcinoma in situ(AIS) cells are often misdiagnosed, and recognizing AIS in cervical cytology is challenging. Here, we present a case of extraperitoneal metastasis 5 years after a missed diagnosis of AIS.Case presentation: We report a 49-year-old Chinese woman who presented with a retroperitoneal mass 5 years after cervical conization for AIS. The retroperitoneal mass was composed of glands lined by malignant mucinous epithelium; these tumors were metastases from her previous AIS which were misdiagonised cervical intraepithelial neoplasia(CIN) III in 2013. The patient is alive and well 2 years after resection of the tumors.Conclusions: An experienced pathologist or multiple pathologists should take part in endocervical AIS diagnosis. We should follow these patients for over 15 years. When Cancer Antigen 125(CA125) or Carcinoembryonic antigen(CEA) levels are elevated, the occurrence of metastases should be strictly monitored.

A Struma Ovarii Associated with Pseudo-Meigs’ Syndrome is Misdiagnosed as Advanced Ovarian Cancer: A Case Report

Introduction: A struma ovarii is a benign monodermal teratoma, composed of mature thyroid tissue. The presentation of this disease with pseudo-Meigs’ syndrome [characterized by ascites, pleural effusions, and elevated cancer antigen-125 (CA-125) levels] may result in an advanced ovarian cancer misdiagnosis. Case Presentation: The patient was a 54-year-old woman with dyspnea, abdominal distention, and pseudo-Meigs’ syndrome. She had a final diagnosis of struma ovarii, misdiagnosed as advanced ovarian cancer. She is currently asymptomatic (after surgery) and has a normal CA-125 level. Conclusions: The preoperative diagnosis of struma ovarii is difficult, and if it presents with pseudo-Meigs’ syndrome, it may be initially misdiagnosed as advanced ovarian cancer. Using the frozen-section procedure, unnecessary extensive surgeries can be prevented.