Ovarian cancer think tank: the use of integrated artificial intelligence and computational biology in ovarian cancer diagnosis and treatment

No Association of BRCA Mutations with Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in Patients Treated for Breast or Ovarian Cancer

Objective To investigate the diagnosis significance of serum HE4 ,CYFRA21-1 , CA125 levels for the benign and malignant varian tumor,and evaluate the value of single detection and combined detection on judging the high risks of ovarian cancer. Methods A total of 45 patients with primary ovarian cancer and 56 patients with benign varian tumor and 50 healthy subjects admitted in Wendeng central hospital whose serum levels of HE4 ,CYFRA21-1 and CA125 were detected by electro-chemiluminescence（ ECL）,any index above the normal limit was setting for positive,the positive rate and coincidence rate of the three indexes in diagnosis of ovarian cancer was analyzed,and the diagnosis values of three indexes in the benign and malignant varian tumors were compared. Results HE4 and CYFRA21-1 levels of ovarian cancer group were significantly higher,compared with the benign tumor group,and healthy contol group and the differences were statistically significant（ P ﹤0. 05 ）,however there was no significant difference between benign tumor group and control group（ P﹥0. 05 ）,for the ma-lignant tumors the specificity and positive predictive value were very high[ HE4（ 100%,100%）,CY-FRA21-1（98. 2%,96. 7%）]and the diagnostic accuracy was relatively high（90. 1%,83. 2%）,com-pared with CA125 the difference was significant（ P﹤0. 05 ）,but both of them the sensitivity was lower than CA125. The CA125 levels were all increased in benign and malignant tumor,only the extent was different,there was significant difference between them（P﹤0. 05）and the difference was also statistical-ly significant in benign and control group（ P﹤0. 05 ）,which can simply distinguish benign and malignant tumors, however the specificity for the diagnosis of ovarian cancer is not very high （75%）and the positive predictive value and diagnostic accuracy was also relatively low（ 72%, 77. 2%）,The sensitivity and accuracy of diagnosis was improved by combining the three indexes and the clinical diagnosis was optimized. Conclusions HE4 ,CYFRA21-1 levels are only increased in malig-nant tumors,and they are mainly used for the diagnosis of ovarian cancer,CA125 levels are all in-creased in benign and malignant tumors,only the extent is different and it can be used for distinguis-hing and diagnosing of benign and malignant tumors. Combining the three indexes can improve the sensitivity and accuracy of the diagnosis of ovarian cancer,and it has important significance for the early diagnosis and treatment of ovarian cancer. Key words: Human epididymis protein 4 Cytokeratin 19 fragment antigen 21-1 CA125 Ovarian cancer Electrochemiluminescence

Objective To investigate the diagnosis significance of human epididymis (HE4), cytokeratin-19-fragment (CYFRA21-1), carbohydrate antigen 199 (CA199) on the malignant ovarian tumor, and to evaluate the value of individual and combined detection in judging high risk ovarian cancer. Methods The serum HE4, CYFRA21-1, CA199 levels of 45 patients with primary ovarian cancer, 56 patients with benign ovarian tumor and 50 healthy check-up women in our hospital were detected by electrochemiluminescence immunoassay (ECL). The positive rates and coincidence rates of them were analyzed and the diagnostic value of them were compared. Results HE4 and CYFRA21-1 levels of ovarian cancer group were significantly higher compared with the benign tumor group and healthy control group and the differences were statistically significant (Z=-8.61, P<0.001; Z=-8.39, P<0.001; Z=-8.60, P<0.001; Z=-8.39, P<0.001), however there is no difference between benign tumor group andcontrol group(Z=-1.31, P=0.189; Z=-1.29, P=0.191). The difference of CA199 between benign tumor group and control group was statistically significant (Z=-8.79, P<0.001). For the malignant tumors, the specificity and positive predictive value of HE4 (99.8%, 99.7%), CYFRA21-1 (99.0%, 96.7%) were very high and the diagnostic accordance rates were relatively high (93.4%, 88.7%), but the sensibilities of them were lower compared with CA199.CA199 was increased both in benign and malignant ovarian tumors with different degrees, but the specificity was not very high (85.8%), and the positive predictive value and the diagnosis accordance rate were low (70.6%, 84.1%). The combined detection of HE4, CYFRA 21-1 and CA199 could improve the sensitivity and of the diagnosis of ovarian cancer (100%) and accuracy (89.4%). Conclusions HE4 and CYFRA21-1 only increas in malignant ovarian tumors, and they are mainly used for the diagnosis of ovarian cancer; CA199 level is increased both in benign and malignant ovarian tumors, but the extent is different and it can be used for distinguishing and diagnosing of benign and malignant ovarian tumors. Combining the three indexes can improve the sensitivity and accuracy of the diagnosis of ovarian cancer, and has an important significance for the early diagnosis and treatment of ovarian cancer. Key words: Ovarian neoplasms; Keratins; Antigens, tumor-associated, carbohydrate; human epididymis protein 4

The aim of this study was to detect the expressions of serum micro-ribonucleic acid (miR)-26b and miR-21 in ovarian cancer patients, and to explore their associations with the diagnosis, clinicopathological parameters and prognosis of ovarian cancer. A total of 86 patients diagnosed with ovarian cancer in our hospital from January 2014 to January 2015 were enrolled in the observation group. Meanwhile, another 86 subjects receiving physical examination in our hospital during the same period were enrolled in the control group. The expressions of serum miR-26b and miR-21 in both groups were detected via Real Time fluorescence-quantitative Polymerase Chain Reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were plotted. Later, the clinical diagnostic value of combined detection of miR-26b and miR-21 in ovarian cancer was analyzed. Moreover, the associations of serum miR-26b and miR-21 expressions with clinicopathological characteristics and prognosis of ovarian cancer patients were explored. The expression of serum miR-26b in ovarian cancer patients was significantly lower than that of healthy subjects, while miR-21 expression was markedly higher in ovarian cancer patients (p<0.05). The area under the ROC curve (AUC), the sensitivity and specificity of miR-26b detection, miR-21 detection and combined detection in the diagnosis of ovarian cancer were 0.753 vs. 0.826 vs. 0.916, 47.2 vs. 76.3 vs. 87.6 and 78.5 vs. 85.6 vs. 90.4, respectively. Therefore, it could be observed that both the sensitivity and specificity of combined detection were remarkably higher than those of single detection (p<0.05). In addition, the expressions of serum miR-26b and miR-21 were associated with clinical stage and lymph node metastasis of ovarian cancer patients, whereas it was not correlated with age and histological type. The 3-year survival rate of patients with high expression of serum miR-26b was significantly higher than that in those with low expression of serum miR-26b. However, the 3-year survival rate of patients with low expression of serum miR-21 was higher than that in those with high expression. MiR-21 is highly expressed, while miR-26b is lowly expressed in the serum of ovarian cancer patients. Both of them may be involved in the incidence and development of ovarian cancer. Furthermore, combined monitoring of serum miR-26b and miR-21 has a certain value in the clinical diagnosis and treatment of ovarian cancer.

Do factors affecting time from symptom onset to diagnosis or treatment of ovarian cancer also affect survival?

Ovarian cancer ranks seventh worldwide and is the third most common type of cancer diagnosed in women in India. Numerous studies have demonstrated that the number of people affected by ovarian cancer is expected to rise significantly in the future. Proactive measures for early cancer detection are essential to prevent death and recurrence. This paper attempts to review the various deep learning (DL) models in ovarian cancer diagnosis, including detecting risk factors, analyzing genomic data sets, predicting disease progression, recurrence, and mortality rates, and identifying correlations and patterns. The patient's electronic health records contain effective analytics on imaging and other types of data that may open the door to more accurate or early identification of ovarian cancer. The taxonomy of the several ways that DL aids in the diagnosis, early detection, and treatment of ovarian cancer will be compiled in this review article. As per the reviews, more research studies have examined the Convolutional Neural Networks (CNNs) approach for the Early Detection and Diagnosis of Ovarian Cancer. This is because CNNs are a popular and potent architecture for image classification tasks because of their capacity to learn spatial and hierarchical features from images effectively. The review article seeks to give future research topics and assess the state-of-the-art application of DL algorithms for ovarian cancer diagnosis.

Objective To investigate the clinical value of human epididymis secretory protein 4 (HE4) in the diagnosis of ovarian cancer. Methods A total of 105 patients with ovarian carcinoma from July 2014 to December 2015 were selected as observation group, and another 90 cases with benign ovarian lesions were selected as control group A and 130 cases of healthy people were selected as control group B, the serum CA125 and HE4 levels of the three groups were determined, and the test result were analysiss. Results The serum level of HE4 in observation group were significantly higher than that in the control group, the difference was significant (P 0.05). Conclusions Serum HE4 is a good marker for ovarian cancer; it can contribute to effective identification of uterine benign and malignant lesions, and have very positive role in the early diagnosis of ovarian cancer, so it is recommended to be further promoted in the clinics to improve the early diagnosis of ovarian cancer. Key words: Ovarian cancer; Human epididymal epithelial secretory protein 4; Pathological diagnosis

BackgroundOvarian Cancer (OC) is a gynecological malignant tumor with an extremely high mortality rate, seriously endangering women’s health. Due to its insidious clinical manifestations, most patients are diagnosed in the advanced stage of the disease. The currently clinically relied CA125 has limited specificity for the early diagnosis of ovarian cancer. Hence, identifying new promising biomarkers is crucial for the early screening, diagnosis, and treatment of ovarian cancer. Based on differential expression analysis, WGCNA and survival analysis, we identified a centromere-associated gene, WDR62, which is highly expressed in ovarian cancer and highly correlated with ovarian cancer, as well as the poor prognosis of ovarian cancer patients with high expression, suggesting that WDR62 may be a potential biomarker for ovarian cancer. Previous studies have shown that WDR62 is closely associated with the occurrence, development and prognosis of a variety of tumors. However, its role in ovarian cancer has not been studied in depth.MethodsUsing combined TCGA and GTEx datasets from the UCSC database, along with WGCNA, and survival analysis, WDR62 was identified as a potential biomarker. GEPIA2 database, GEO database, qRT-PCR, and Western blot proved the expression of WDR62. Enrichment analysis, cell transfection, Western blots and CCK8 demonstrated the regulatory mechanism of WDR62, and the detailed mechanism of WDR62 involvement in the occurrence and development of ovarian cancer was predicted by interaction analysis and correlation analysis.ResultsWDR62 was highly expressed in ovarian cancer cells compared to normal ovarian epithelial cells, both at the RNA and protein levels. Patients with high WDR62 expression had a poor survival prognosis. Upon WDR62 knockdown, the expression of cell cycle-related proteins CDK1 and C-Myc decreased in ovarian cancer cells, and the cell proliferative capacity was decreased. Based on bioinformatic analysis, it was hypothesized that WDR62 might mediate the JNK signaling pathway by interacting with MAPK8, thus affecting ovarian cancer progression through cell cycle regulation.ConclusionsWDR62 is overexpressed in ovarian cancer and is closely related to the prognosis of ovarian cancer patients. WDR62 promotes ovarian cancer progression by regulating the cell cycle and may influence its development through interaction with MAPK8 to mediate the JNK signaling pathway. These findings suggest that WDR62 could be a potential target for the early screening, diagnosis, and treatment of ovarian cancer.

Ovarian cancer is the malignant tumor with the highest mortality rate in the female reproductive system, enormous socio-economic burden, and limited effective drug therapy. There is an urgent need to find novel effective drugs for ovarian cancer therapy. Our previous in vitro studies demonstrate that ivermectin effectively inhibits ovarian cancer cells and affects energy metabolism pathways. This study aims to clarify in vivo mechanisms and therapeutic targets of ivermectin in the treatment of ovarian cancer to establish predictive biomarkers, guide personalized treatments, and improve preventive strategies in the framework of 3P medicine. A TOV-21G tumor-bearing mouse model was constructed based on histopathological data and biochemical parameters. TMT-based proteomic analysis was performed on tumor tissues from the different treatment groups. All significantly differentially abundant proteins were characterized by hierarchical clustering, Gene Ontology (GO) enrichment analyses, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, the data were integrated and analyzed with the proteomic data of clinical ovarian cancer tissues from our previous study and the proteomic data of ivermectin intervention in ovarian cancer cells to identify key regulators of ivermectin. Ivermectin (10mg/kg) had a significant anti-ovarian cancer effect in mice, with a tumor inhibitory rate of 61.5%. Molecular changes in tumor tissue of ivermectin-treated mice were established, and protein-protein interaction (PPI) analysis showed that the main differential pathway networks included the TCA cycle, propanoate metabolism, 2-0xocarboxyacid metabolism, and other pathways. Integrating our previous clinical ovarian cancer tissue and cell experimental data, this study found that ivermectin significantly interfered with the energy metabolic pathways of ovarian cancer, including glycolysis, TCA cycle, oxidative phosphorylation, and other related pathways. This study evaluated the anti-ovarian cancer effect in vitro and in vivo, and its specific regulatory effect on energy metabolism. The expressions of drug target molecules in the energy metabolism pathway of ovarian cancer will be used to guide the diagnosis and prevention of ovarian cancer. The significant efficacy of ivermectin will be applied to the treatment of ovarian cancer and personalized medication. This has guiding significance for the clinical diagnosis, treatment, personalized medication, and prognosis evaluation of ovarian cancer. The online version contains supplementary material available at 10.1007/s13167-024-00385-1.

Ovarian cancer is frequently occurring and fatal for women. CA-125 is important in the screening, diagnosis, and treatment of ovarian cancer. This review study was conducted to explore the influence of CA-125 in addressing ovarian cancer. To investigate the role of CA-125 in ovarian cancer, we conducted a comprehensive search for high-quality articles in the Medline, Web of Science Core Collection and Scopus databases using the keywords "ovarian cancer," "ovarian carcinoma," "ovarian neoplasms," and "CA-125" from the 2000 to 2024. We included full-text, peer-reviewed articles in English with relevant keywords published since 2000. We excluded case reports, commentaries, letters to the editor, books, case series, systematic reviews, animal studies, and articles that were not accessible in full text. After screening the 7947 records, 88 studies were included in this review. In the literature review, it was found that researchers utilized CA-125 for diagnosing ovarian cancer, its predicting, evaluating treatment response, assessing ovarian cancer survival, and early detection of recurrence. In some cases, researchers employed additional tumor markers alongside CA-125 to enhance the test's sensitivity. CA-125 has become a pivotal marker for ovarian cancer. Its role in the diagnosis, treatment, and ongoing assessment of ovarian cancer cannot be overstated. Continuous monitoring of CA-125 levels can provide comprehensive insights, and categorizing patients as low-risk or high-risk based on CA-125 levels could lead to better outcomes. Integrating CA-125 with other biomarkers may enhance the accuracy of the test and elevate its relevance in patient care.

ObjectivesThis study aimed to explore the adverse effects of chemotherapeutic agents used in the treatment of ovarian and cervical cancer by analysing patients’ views posted in online discussion forums.MethodUK-centred online...

Ovarian cancer is a markedly heterogeneous malignancy characterized by various histological subtypes. Molecular biomarkers have been indicated to serve significant functions in the early diagnosis and treatment of early-stage ovarian cancer. However, the detailed mechanism underlying the tumorigenesis of ovarian cancer remains unclear. The present study aimed to identify a novel long non-coding RNA in patients with ovarian cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) was markedly downregulated in patients with ovarian cancer and in cultured human ovarian cancer cells. Knockdown of NNT-AS1 in the human ovarian cancer cell lines HO-8910 and SK-OV-3 promoted colony formation and arrested the cell cycle at G0/G1 phase. Furthermore, Transwell demonstrated that the downregulation of NNT-AS1 increased cell migration and invasion by ~60 and 70%, respectively, in HO-8910 and SK-OV-3 cells. Furthermore, cell apoptosis was inhibited by the transfection of siNNT-AS1 in the two cell lines, whereas the relative activities of caspase-3 and caspase-9 were decreased. These results indicated a protective function of NNT-AS1 in human ovarian cancer, providing novel insights into the diagnosis and treatment of ovarian cancer in clinical settings.

Targeting of the mechanisms responsible for ovarian cancer recurrence and chemoresistance serves the two most pressing needs for the clinical management of this disease: prevent recurrence in women who are in remission and provide effective treatment for patients who have recurred (1). Ovarian cancer recurrence is due to the presence of a relatively small population of cancer cells (floating in the abdominal cavity as spheroids and circulating in the bloodstream) that were not removed during surgery and was able to survive chemotherapy treatment (2-4). These cells, after a period of latency, grow back and cause recurrent and chemoresistant ovarian cancer. Recent evidences suggest that spheroids’ and cancer cells’ resistance to conventional chemotherapy is due to their ability to increase mitochondrial respiration as a way to survive the highly hostile tumor microenvironment caused by chemotherapy and hypoxia (5-9). To prevent recurrence and to treat chemoresistance we need to: 1) find the “Achille’s heel” of the small population of cancer cells that are capable of escaping chemotherapy and kill them, and 2) use therapeutic strategies that are already FDA approved because their known toxicology and pharmacology makes them ideal repurposed drugs rapidly implementable in the clinics. We propose that: a) ovarian cancer spheroids and chemoresistant metastasis share the unique Achille’s heel of having high dependency upon mitochondrial activity, b) targeting of mitochondrial activity leads to effective killing of ovarian cancer cells in spheroids and in chemoresistant metastasis with no toxicity on normal cells, and c) the FDA-approved antimitochondrial antibiotics inhibit cancer cells’ mitochondrial activity and can safely and effectively be used to prevent ovarian cancer recurrence and to treat chemoresistance (10, 11). This research is clinically relevant in that antimitochondrial antibiotics can be quickly implemented in the clinic as a mantainance therapy for women in remission and as a combination therapy for patients with recurrent and chemoresistant ovarian cancer. Of note, several antimitochondrial antibiotics have long half-life, are well tolerated, and are affordable, rendering them the ideal repurposed drug.

Ovarian cancer is one of the common malignant tumors, the mortality of ovarian cancer ranks first in gynecologic oncology. More and more researches suggest that ovarian cancer should be classified as stem cell diseases. The early diagnosis and early treatment of ovarian cancer depend on the detection and recognition of more ovarian neoplasm stem cell markers. In this review, we will make a review from the aspects of cancer stem cell (CSC) theory origin and its evolution, the discovery of ovarian neoplasms stem cells, ovarian neoplasms stem cells and the relationship between the ovarian neoplasms and its purification, ovarian neoplasms stem cell markers in the early diagnosis and treatment of ovarian cancer, and so on. Key words: Ovarian neoplasms; Numb protein; Cancer stem cells markers; Diagnosis; Treatment

Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides selected from a random single-stranded nucleic acid library using systematic evolution of ligands by exponential enrichment technology. To allow them to bind to molecular targets with the same specificity and precision as that of antibodies, aptamers are folded into secondary or tertiary structures. However, compared to antibodies, aptamers are not immunogenic and are easier to synthesize. Furthermore, they are chemically modified, which protects them from degradation by nucleases. Hence, due to their stability and favorable targeting ability, aptamers are promising for the diagnosis and treatment of diseases. Ovarian cancer has the worst prognosis among all gynecological diseases and is usually diagnosed at the medium and advanced stages due to its nonspecific symptoms. Relapse is common, even if patients receive a standard therapeutic regimen including surgery and chemotherapy; simultaneously, drug resistance and adverse effects are reported in a several patients. Therefore, the safer and more efficient diagnostic and treatment method for ovarian cancer is imperative. Scientists have been trying to utilize aptamer technology for the early diagnosis and accurate treatment of ovarian cancer and some progress has been made in this field. This review discusses the screening of nucleic acid aptamers by targeting ovarian cancer cells and the application of aptamers in the diagnosis and treatment of ovarian cancer.