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Momenimovahed Z, Mazidimoradi A, Allahqoli L, Salehiniya H. The Role of CA-125 in the Management of Ovarian Cancer: A Systematic Review. Cancer Rep (Hoboken) 2025; 8:e70142. [PMID: 40067023 PMCID: PMC11894717 DOI: 10.1002/cnr2.70142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 01/15/2025] [Accepted: 01/29/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
| | | | - Leila Allahqoli
- Midwifery DepartmentMinistry of Health and Medical EducationTehranIran
| | - Hamid Salehiniya
- Department of Epidemiology and Biostatistics, School of Health, Social Determinants of Health Research CenterBirjand University of Medical SciencesBirjandIran
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Jankowska-Lombarska M, Grabowska-Derlatka L, Kraj L, Derlatka P. Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging in Magnetic Resonance in the Assessment of Peritoneal Recurrence of Ovarian Cancer in Patients with or Without BRCA Mutation. Cancers (Basel) 2024; 16:3738. [PMID: 39594694 PMCID: PMC11591656 DOI: 10.3390/cancers16223738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 11/01/2024] [Accepted: 11/03/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND The aim of this study was to determine the differences in diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) parameters between patients with peritoneal high-grade serous ovarian cancer (HGSOC) recurrence with BRCA mutations (BRCAmut) or BRCA wild type (BRCAwt). MATERIALS AND METHODS We retrospectively analyzed the abdominal and pelvic magnetic resonance (MR) images of 43 patients suspected of having recurrent HGSOC, of whom 18 had BRCA1/2 gene mutations. Patients underwent MRI examination via a 1.5 T MRI scanner, and the analyzed parameters were as follows: apparent diffusion coefficient (ADC), time to peak (TTP) and perfusion maximum enhancement (Perf. Max. En.). RESULTS The mean ADC in patients with BRCAwt was lower than that in patients with BRCAmut: 788.7 (SD: 139.5) vs. 977.3 (SD: 103), p-value = 0.00002. The average TTP value for patients with BRCAwt was greater than that for patients with mutations: 256.3 (SD: 50) vs. 160.6 (SD: 35.5), p-value < 0.01. The Perf. Max. En. value was lower in the BRCAwt group: 148.6 (SD: 12.3) vs. 233.6 (SD: 29.2), p-value < 0.01. CONCLUSION Our study revealed a statistically significant correlation between DWI and DCE parameters in examinations of peritoneal metastasis in patients with BRCA1/2 mutations. Adding DCE perfusion to the MRI protocol for ovarian cancer recurrence in patients with BRCAmut may be a valuable tool.
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Affiliation(s)
| | | | - Leszek Kraj
- Department of Oncology, Medical University of Warsaw, Banacha 1a St., 02-097 Warsaw, Poland;
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, 01-447 Magdalenka, Poland
| | - Pawel Derlatka
- Second Department of Obstetrics and Gynecology, Medical University of Warsaw, Karowa 2 St., 00-315 Warsaw, Poland;
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Ma S, Li R, Li G, Wei M, Li B, Li Y, Ha C. Identification of a G-protein coupled receptor-related gene signature through bioinformatics analysis to construct a risk model for ovarian cancer prognosis. Comput Biol Med 2024; 178:108747. [PMID: 38897150 DOI: 10.1016/j.compbiomed.2024.108747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 05/31/2024] [Accepted: 06/08/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Ovarian cancer (OV) is a common malignant tumor of the female reproductive system with a 5-year survival rate of ∼30 %. Inefficient early diagnosis and prognosis leads to poor survival in most patients. G protein-coupled receptors (GPCRs, the largest family of human cell surface receptors) are associated with OV. We aimed to identify GPCR-related gene (GPCRRG) signatures and develop a novel model to predict OV prognosis. METHOD We downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic GPCRRGs were screened using least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and a prognostic model was constructed. The predictive ability of the model was evaluated by Kaplan-Meier (K-M) survival analysis. The levels of GPCRRGs were examined in normal and OV cell lines using quantitative reverse-Etranscription polymerase chain reaction. The immunological characteristics of the high- and low-risk groups were analyzed using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. RESULTS Based on the risks scores, 17 GPCRRGs were associated with OV prognosis. CXCR4, GPR34, LGR6, LPAR3, and RGS2 were significantly expressed in three OV datasets and enabled accurate OV diagnosis. K-M analysis of the prognostic model showed that it could differentiate high- and low-risk patients, which correspond to poorer and better prognoses, respectively. GPCRRG expression was correlated with immune infiltration rates. CONCLUSIONS Our prognostic model elaborates on the roles of GPCRRGs in OV and provides a new tool for prognosis and immune response prediction in patients with OV.
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Affiliation(s)
- Shaohan Ma
- Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Ruyue Li
- Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Guangqi Li
- Medical Laboratory Center, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Meng Wei
- Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Bowei Li
- Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Yongmei Li
- Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Chunfang Ha
- Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China; Key Laboratory of Fertility Preservation & Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, 750000, China.
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Du K, Li Q, Huang J, Chan DW, Li J, Chang X, Wang H, Tang J, Yang Q. An increase of serum CA-125 to two times of nadir level strongly predicts the image-identified relapse of serous ovarian cancer. Sci Rep 2024; 14:14986. [PMID: 38951620 PMCID: PMC11217381 DOI: 10.1038/s41598-024-65760-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 06/24/2024] [Indexed: 07/03/2024] Open
Abstract
Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the association between a biochemical relapse (only the elevation of CA125) and an image-identified relapse to predict the relapsed lesions better. 162 patients who achieved complete clinical response were enrolled from women diagnosed with stage I-IV serous ovarian, tubal, and peritoneal cancers from January 2013 to June 2019 at our center. The CA125 level of 2 × nadir was defined as the indicator of image-identified relapse (P < 0.001). Compared to CA125 level exceeding 35 U/ml, the 2 × nadir of CA125 improve the sensitivity of image-identified relapse (84.9% vs 67.4%, P < 0.001); the 2 × nadir value can act as an earlier warning relapse signal with a longer median time to image-identified relapse (2.7 vs. 0 months, P < 0.001). Of the relapsed population, there was no difference of CA125 changing trend between the neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) group after initial treatment. Compared with 35 U/ml, CA125 reaching 2 × nadir during the follow-up process might be a more sensitive and early relapse signal in patients with serous OvCa. This criterion may help guide patients to be recommended for imaging examination to detect potential relapse in time.
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Affiliation(s)
- Kaiwen Du
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China
| | - Qian Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China
| | - Jin Huang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, The Chinese University of Hong Kong-Shenzhen, Shenzhen, People's Republic of China
- Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - David Wai Chan
- School of Medicine, The Chinese University of Hong Kong-Shenzhen, Shenzhen, People's Republic of China
| | - Jinjin Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China
| | - Xiaoxia Chang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China
| | - Hanjie Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China
| | - Junying Tang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China.
| | - Qiyu Yang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chong Qing, 400000, People's Republic of China.
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Krishnan SR, Sharma D, Nazeer Y, Bose M, Rajkumar T, Jayaraman G, Madaboosi N, Gromiha MM. rAbDesFlow: a novel workflow for computational recombinant antibody design for healthcare engineering. Antib Ther 2024; 7:256-265. [PMID: 39262441 PMCID: PMC11384895 DOI: 10.1093/abt/tbae018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 05/11/2024] [Indexed: 09/13/2024] Open
Abstract
Recombinant antibodies (rAbs) have emerged as a promising solution to tackle antigen specificity, enhancement of immunogenic potential and versatile functionalization to treat human diseases. The development of single chain variable fragments has helped accelerate treatment in cancers and viral infections, due to their favorable pharmacokinetics and human compatibility. However, designing rAbs is traditionally viewed as a genetic engineering problem, with phage display and cell free systems playing a major role in sequence selection for gene synthesis. The process of antibody engineering involves complex and time-consuming laboratory techniques, which demand substantial resources and expertise. The success rate of obtaining desired antibody candidates through experimental approaches can be modest, necessitating iterative cycles of selection and optimization. With ongoing advancements in technology, in silico design of diverse antibody libraries, screening and identification of potential candidates for in vitro validation can be accelerated. To meet this need, we have developed rAbDesFlow, a unified computational workflow for recombinant antibody engineering with open-source programs and tools for ease of implementation. The workflow encompasses five computational modules to perform antigen selection, antibody library generation, antigen and antibody structure modeling, antigen-antibody interaction modeling, structure analysis, and consensus ranking of potential antibody sequences for synthesis and experimental validation. The proposed workflow has been demonstrated through design of rAbs for the ovarian cancer antigen Mucin-16 (CA-125). This approach can serve as a blueprint for designing similar engineered molecules targeting other biomarkers, allowing for a simplified adaptation to different cancer types or disease-specific antigens.
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Affiliation(s)
- Sowmya Ramaswamy Krishnan
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
| | - Divya Sharma
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
| | - Yasin Nazeer
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
| | - Mayilvahanan Bose
- Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai 600020, India
| | - Thangarajan Rajkumar
- Department of Applied Mechanics and Biomedical Engineering, Indian Institute of Technology Madras, Chennai 600036, India
- MedGenome, Bengaluru 560099, Karnataka, India
- Department of Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences, Kochi 682041, Kerala, India
| | - Guhan Jayaraman
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
| | - Narayanan Madaboosi
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
| | - M Michael Gromiha
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
- International Research Frontiers Initiative, School of Computing, Tokyo Institute of Technology, Yokohama 226-8501, Japan
- School of Computing, National University of Singapore (NUS), Singapore 119077, Singapore
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Zhang XY, Hong LL, Ling ZQ. MUC16: clinical targets with great potential. Clin Exp Med 2024; 24:101. [PMID: 38758220 PMCID: PMC11101557 DOI: 10.1007/s10238-024-01365-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 04/29/2024] [Indexed: 05/18/2024]
Abstract
Mucin 16 (MUC16) is a membrane-bound mucin that is abnormally expressed or mutated in a variety of diseases, especially tumors, while being expressed in normal body epithelium. MUC16 and its extracellular components are often important cancer-related biomarkers. Abnormal expression of MUC16 promotes tumor progression through mesenchymal protein, PI3K/AKT pathway, JAK2/STAT3 pathway, ERK/FBW7/c-Myc, and other mechanisms, and plays an important role in the occurrence and development of tumors. In addition, MUC16 also helps tumor immune escape by inhibiting T cells and NK cells. Many drugs and trials targeting MUC16 have been developed, and MUC16 may be a new direction for future treatments. In this paper, the mechanism of action of MUC16 in the development of cancer, especially in the immune escape of tumor, is introduced in detail, indicating the potential of MUC16 in clinical treatment.
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Affiliation(s)
- Xin-Yu Zhang
- Zhejiang Cancer Institute, Zhejiang Cancer Hospital, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China
- The Second Clinical Medical College of Zhejiang, Chinese Medicine University, Hangzhou, 310053, China
| | - Lian-Lian Hong
- Zhejiang Cancer Institute, Zhejiang Cancer Hospital, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China
| | - Zhi-Qiang Ling
- Zhejiang Cancer Institute, Zhejiang Cancer Hospital, No.1 Banshan East Rd., Gongshu District, Hangzhou, 310022, Zhejiang, China.
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China.
- The Second Clinical Medical College of Zhejiang, Chinese Medicine University, Hangzhou, 310053, China.
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Xing XY, Zhang W, Liu LY, Han LP. Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma. World J Clin Cases 2024; 12:1111-1119. [PMID: 38464918 PMCID: PMC10921297 DOI: 10.12998/wjcc.v12.i6.1111] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/28/2023] [Accepted: 01/22/2024] [Indexed: 02/20/2024] Open
Abstract
BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare. AIM To enhance our clinical understanding of neuroendocrine carcinoma (NEC) of the ovary. METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary, analyzing clinicopathological characteristics, treatment modalities, and survival status. RESULTS The median age at diagnosis was 34.5 years (range: 20 to 62 years). Among the 12 cases, 9 were small cell carcinoma of the ovary and 3 were large cell NEC. Five cases were stage I tumors, one case was stage IV, and six cases were stage III. Eleven patients underwent surgery as part of their treatment. All patients received adjuvant chemotherapy. Among the 12 patients, one patient received radiotherapy, and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy. The median progression-free survival was 13 months, and the median overall survival was 19.5 months. Four cases remained disease-free, while eight cases experienced tumor recurrence, including three cases that resulted in death due to disease recurrence. CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes. Surgical resection remains the mainstay of treatment, with some patients benefiting from adjuvant chemoradiation therapy.
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Affiliation(s)
- Xiao-Yu Xing
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Wei Zhang
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Li-Ya Liu
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Li-Ping Han
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
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Mayenga DB, Degu A. An assessment of survival outcomes among ovarian cancer patients at the National and Referral Hospital in Kenya. Cancer Rep (Hoboken) 2024; 7:e1986. [PMID: 38351536 PMCID: PMC10864719 DOI: 10.1002/cnr2.1986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 01/02/2024] [Accepted: 01/15/2024] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND Ovarian cancer has been shown to have poor survival outcomes attributed to late presentation. In Kenya, information on the survival outcomes of ovarian cancer patients is scarce. Therefore, the objective of this study was to examine the survival outcomes among patients with ovarian cancer treated at Kenyatta National Hospital (KNH). AIMS A hospital-based retrospective cohort study was performed at KNH to examine the survival outcomes of 112 ovarian cancer patients. The study employed a structured data abstraction tool to acquire patients' relevant socio-demographic and clinical characteristics from the patient's medical records. The data obtained were analyzed using SPSS version 29.0 statistical software. Kaplan-Meier and Cox regression analyses were used to determine the survival outcome and predictors of mortality among ovarian cancer patients, respectively. METHODS AND RESULTS The mean age of the patients in this study was 51.28 ± 14.24 years. Most patients (59.8%) had evidence of distant metastasis during the follow-up period. One-third (33%) of patients were deceased. The mean-cancer-specific survival time among the study participants was 40.0 ± 3.0 months. The 5-year survival rate was 44%, with most patients experiencing disease progression during the last follow-up. Combination therapy (p < .001) was the only statistically significant predictor of mortality in ovarian cancer patients. CONCLUSION The study found that the 5-year survival rate among ovarian cancer patients was poor, with most patients experiencing disease progression during the last follow-up period.
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Affiliation(s)
- Diana Bironga Mayenga
- School of Pharmacy and Health Sciences, Department of Pharmaceutics and Pharmacy PracticeUnited States International University‐AfricaNairobiKenya
| | - Amsalu Degu
- School of Pharmacy and Health Sciences, Department of Pharmaceutics and Pharmacy PracticeUnited States International University‐AfricaNairobiKenya
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Chen B, Zhao L, Yang R, Xu T. The recent advancements of ferroptosis in the diagnosis, treatment and prognosis of ovarian cancer. Front Genet 2023; 14:1275154. [PMID: 38028615 PMCID: PMC10665572 DOI: 10.3389/fgene.2023.1275154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 10/26/2023] [Indexed: 12/01/2023] Open
Abstract
Ovarian cancer affects the female reproductive system and is the primary cause of cancer related mortality globally. The imprecise and non-specific nature of ovarian cancer symptoms often results in patients being diagnosed at an advanced stage, with metastatic lesions extending beyond the ovary. This presents a significant clinical challenge and imposes a substantial economic burden on both patients and society. Despite advancements in surgery, chemotherapy, and immunotherapy, the prognosis for most patients with ovarian cancer remains unsatisfactory. Therefore, the development of novel treatment strategies is imperative. Ferroptosis, a distinct form of regulated cell death, characterized by iron-dependent lipid peroxidation, differs from autophagy, apoptosis, and necrosis, and may hold promise as a novel cell death. Numerous studies have demonstrated the involvement of ferroptosis in various conventional signaling pathways and biological processes. Recent investigations have revealed the significant contribution of ferroptosis in the initiation, progression, and metastasis of diverse malignant tumors, including ovarian cancer. Moreover, ferroptosis exhibits a synergistic effect with chemotherapy, radiotherapy, and immunotherapy in restraining the proliferation of ovarian cancer cells. The aforementioned implies that ferroptosis holds considerable importance in the management of ovarian cancer and has the potential to serve as a novel therapeutic target. The present review provides a comprehensive overview of the salient features of ferroptosis, encompassing its underlying mechanisms and functional role in ovarian cancer, along with the associated signaling pathways and genes. Furthermore, the review highlights the prospective utility of ferroptosis in the treatment of ovarian cancer.
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Affiliation(s)
| | | | | | - Tianmin Xu
- The Second Hospital of Jilin University, Changchun, China
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Son JH, Kong TW, Park SJ, Lee EJ, Kim HS, Kim NK, Kim Y, Hwang WY, Suh DH, Kim TH, Yang EJ, Shim SH, Chang SJ. Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001). J Surg Oncol 2023; 128:645-652. [PMID: 37126413 DOI: 10.1002/jso.27303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 04/16/2023] [Accepted: 04/21/2023] [Indexed: 05/02/2023]
Abstract
BACKGROUND To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.
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Affiliation(s)
- Joo-Hyuk Son
- Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea
| | - Tae-Wook Kong
- Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea
| | - Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Nam Kyeong Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yeorae Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Woo Yeon Hwang
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Hoon Suh
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Tae Hun Kim
- Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Eun Jung Yang
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea
| | - Seung-Hyuk Shim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea
| | - Suk-Joon Chang
- Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea
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Construction of Ovarian Cancer Prognostic Model Based on the Investigation of Ferroptosis-Related lncRNA. Biomolecules 2023; 13:biom13020306. [PMID: 36830675 PMCID: PMC9953467 DOI: 10.3390/biom13020306] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/23/2022] [Accepted: 01/04/2023] [Indexed: 02/10/2023] Open
Abstract
(1) Background: Ovarian cancer (OV) has the high mortality rate among gynecological cancers worldwide. Inefficient early diagnosis and prognostic prediction of OV leads to poor survival in most patients. OV is associated with ferroptosis, an iron-dependent form of cell death. Ferroptosis, believed to be regulated by long non-coding RNAs (lncRNAs), may have potential applications in anti-cancer treatments. In this study, we aimed to identify ferroptosis-related lncRNA signatures and develop a novel model for predicting OV prognosis. (2) Methods: We downloaded data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression, and Gene Expression Omnibus (GEO) databases. Prognostic lncRNAs were screened by least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, and a prognostic model was constructed. The model's predictive ability was evaluated by Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) curves. The expression levels of these lncRNAs included in the model were examined in normal and OV cell lines using quantitative reverse transcriptase polymerase chain reaction. (3) Results: We constructed an 18 lncRNA prognostic prediction model for OV based on ferroptosis-related lncRNAs from TCGA patient samples. This model was validated using TCGA and GEO patient samples. KM analysis showed that the prognostic model was able to significantly distinguish between high- and low-risk groups, corresponding to worse and better prognoses. Based on the ROC curves, our model shows stronger prediction precision compared with other traditional clinical factors. Immune cell infiltration, immune checkpoint expression levels, and Tumor Immune Dysfunction and Exclusion analyses are also insightful for OV immunotherapy. (4) Conclusions: The prognostic model constructed in this study has potential for improving our understanding of ferroptosis-related lncRNAs and providing a new tool for prognosis and immune response prediction in patients with OV.
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Cheng Z, Chen Y, Huang H. Identification and Validation of a Novel Prognostic Signature Based on Ferroptosis-Related Genes in Ovarian Cancer. Vaccines (Basel) 2023; 11:vaccines11020205. [PMID: 36851083 PMCID: PMC9962729 DOI: 10.3390/vaccines11020205] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 01/08/2023] [Accepted: 01/10/2023] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Ovarian cancer is the most lethal gynecological tumor, with a poor prognosis due to the lack of early symptoms, resistance to chemotherapy, and recurrence. Ferroptosis belongs to the regulated cell death family, and is characterized by iron-dependent processes. Here, comprehensive bioinformatics analysis was applied to explore a valuable prognostic model based on ferroptosis-related genes, which was further validated in clinical OC samples. METHODS mRNA data of normal and ovarian tumor samples were obtained separately from the GTEx and TCGA databases. The least absolute shrinkage and selection operator (LASSO) cox regression was applied to construct the prognostic model based on ferroptosis-associated genes. Expression of ALOX12 in OC cell lines, as well as cell functions, including proliferation and migration, were examined. Finally, the prognostic efficiency of the model was assessed in the clinical tissues of OC patients. RESULTS A gene signature consisting of ALOX12, RB1, DNAJB6, STEAP3, and SELENOS was constructed. The signature divided TCGA, ICGC, and GEO cohorts into high-risk and low-risk groups separately. Receiver operating characteristic (ROC) curves and independent prognostic factor analysis were carried out, and the prognostic efficacy was validated. The expression levels of ALOX12 in cell lines were examined. Inhibition of ALOX12 attenuated cell proliferation and migration in HEY cells. Moreover, the prognostic value of ALOX12 expression was examined in clinical samples of OC patients. CONCLUSION This work constructed a novel ferroptosis-associated gene model. Furthermore, the clinical predictive role of ALOX12 was identified in OC patients, suggesting that ALOX12 might act as a potential prognostic tool and therapeutic target for OC patients.
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Affiliation(s)
- Zhe Cheng
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yongheng Chen
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Huichao Huang
- Department of Infectious Disease, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Correspondence:
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Qian L, Chen Y, Peng M, Xia Y, Zhou T, Hong J, Ding S. The Importance of Marital Status in the Morbidity and Prognosis of Lung Metastasis in Newly Diagnosed Ovarian Cancer. J Cancer 2023; 14:1024-1038. [PMID: 37151400 PMCID: PMC10158508 DOI: 10.7150/jca.83017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 03/25/2023] [Indexed: 05/09/2023] Open
Abstract
Objective: The study aimed to evaluate the risk factors for the morbidity and prognosis of lung metastases (LM) in patients with newly diagnosed ovarian cancer (OC), and further explore the important role of marital status. Materials and methods: Based on the Surveillance, Epidemiology, and End Results (SEER) dataset, OC patients from 2010 and 2019 were retrospectively analyzed. Logistic regression analysis and Kaplan-Meier method were applied to evaluate the vital factors of incidence and survival outcome in LM population. Cox regression analysis was performed to identify risk factors for the prognosis of OC patients with LM. The predictive potential was showed by two established nomograms and examined by the concordance index (C-index), calibration curves, the area under the curve (AUC), decision curve analyses (DCAs) and clinical impact curves (CICs). Results: There are 25,202 eligible OC patients were enrolled in the study, the morbidity of LM at 5.61%. Multivariable logistic regression models illustrated that chemotherapy (P<0.01), surgical treatment of bilateral or more areas (P<0.01), T stage (P<0.01), N1 stage (P<0.01), bone metastasis (P<0.01), brain metastasis (P<0.01) and liver metastasis (P<0.01) were all significantly connected with LM in OC. Multivariable Cox regression analyses illustrated that unmarried, radiotherapy, elder people and positive cancer antigen 125 (CA-125) were significantly associated with shorter survival time, while chemotherapy made contributions to improve survival. Our study found that marital relationships promoted LM and was associated with the better prognosis, while unmarried patients had the opposite results. With the further development of our research, the cross-action of social, economic and psychological factors together determined the great impact of marital status on the morbidity and prognosis of OC patients combined with LM. Finally, the stability of the models was proved by internal verification. Conclusion: The population-based cohort study provides references for guiding clinical screening and individualized treatment of OC patients with LM. Under the influence of society and economy, marital status is closely related to the morbidity and prognosis of OC, which can be an important direction to explore the risk of OC lung metastasis in the future.
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Affiliation(s)
- Lihui Qian
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Yixin Chen
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Mingying Peng
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Yuwei Xia
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Tianye Zhou
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Jiana Hong
- Department of Nursing, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, China
- ✉ Corresponding authors: Shuning Ding, ; Jiana Hong,
| | - Shuning Ding
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
- ✉ Corresponding authors: Shuning Ding, ; Jiana Hong,
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Hua Y, Yin H, Liu X, Xie J, Zhan W, Liang G, Shen Y. Salt-Inducible Kinase 2-Triggered Release of Its Inhibitor from Hydrogel to Suppress Ovarian Cancer Metastasis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2202260. [PMID: 35618488 PMCID: PMC9353504 DOI: 10.1002/advs.202202260] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Indexed: 05/27/2023]
Abstract
Salt-inducible kinase 2 (SIK2) is a promising target for ovarian cancer therapy due to its critical role in tumorigenesis and progression. Currently available SIK2 inhibitors have shown remarkable therapeutic effects on ovarian cancers in preclinical studies. However, direct administration of the SIK2 inhibitors may bring significant off-target effect, limiting their clinical applications. In this work, by rational design of a hydrogelator Nap-Phe-Phe-Glu-Glu-Leu-Tyr-Arg-Thr-Gln-Ser-Ser-Ser-Asn-Leu-OH (Nap-S) to coassemble a SIK2 inhibitor HG-9-91-01 (HG), a SIK2-responsive supramolecular hydrogel (Gel Nap-S+HG) for local administration and SIK2-responsive release of HG is reported to efficiently suppress ovarian cancer metastasis. Under the activation of SIK2 overexpressed in ovarian cancers, Nap-S in the hydrogel is phosphorylated to yield hydrophilic Nap-Phe-Phe-Glu-Glu-Leu-Tyr-Arg-Thr-Gln-Ser(H2 PO3 )-Ser-Ser-Asn-Leu (Nap-Sp), triggering the disassembly of the hydrogel and a responsive release of the inhibitor. Cell experiments indicate that sustained release of HG from Gel Nap-S+HG induce a prominent therapeutic effect on cancer cells by inhibiting SIK2 and phosphorylation of their downstream signaling molecules. Animal experiments demonstrate that, compared with those tumor model mice treated with free HG, Gel Nap-S+HG-treatment mice show an enhanced inhibition on ovarian tumor growth and metastasis. It is anticipated that the Gel Nap-S+HG can be applied for ovarian cancer therapy in clinic in the near future.
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Affiliation(s)
- Yue Hua
- Department of Obstetrics and GynaecologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu210009China
| | - Han Yin
- Department of Obstetrics and GynaecologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu210009China
| | - Xiaoyang Liu
- State Key Laboratory of BioelectronicsSchool of Biological Science and Medical EngineeringSoutheast University2 Sipailou RoadNanjing210096China
| | - Jinbing Xie
- Department of Obstetrics and GynaecologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu210009China
| | - Wenjun Zhan
- State Key Laboratory of BioelectronicsSchool of Biological Science and Medical EngineeringSoutheast University2 Sipailou RoadNanjing210096China
| | - Gaolin Liang
- State Key Laboratory of BioelectronicsSchool of Biological Science and Medical EngineeringSoutheast University2 Sipailou RoadNanjing210096China
| | - Yang Shen
- Department of Obstetrics and GynaecologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu210009China
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Folsom SM, Mumford B, Lemon L, Taylor S. CA-125 monitoring in gynecologic cancer patients with COVID-19: A case series. Gynecol Oncol Rep 2022; 42:101029. [PMID: 35747786 PMCID: PMC9212932 DOI: 10.1016/j.gore.2022.101029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/06/2022] [Accepted: 06/09/2022] [Indexed: 11/29/2022] Open
Affiliation(s)
- Susan M. Folsom
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, United States
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, United States
- Corresponding author.
| | - Brigid Mumford
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, United States
| | - Lara Lemon
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, United States
- University of Pittsburgh Medical Center, Department of Clinical Analytics, United States
| | - Sarah Taylor
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, United States
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, United States
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Wang Z, Chen G, Dai F, Liu S, Hu W, Cheng Y. Identification and Verification of Necroptosis-Related Gene Signature With Prognosis and Tumor Immune Microenvironment in Ovarian Cancer. Front Immunol 2022; 13:894718. [PMID: 35812403 PMCID: PMC9265217 DOI: 10.3389/fimmu.2022.894718] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Abstract
Ovarian cancer is the most lethal heterogeneous disease among gynecological tumors with a poor prognosis. Necroptosis, the most studied way of death in recent years, is different from apoptosis and pyroptosis. It is a kind of regulated programmed cell death and has been shown to be closely related to a variety of tumors. However, the expression and prognosis of necroptosis-related genes in ovarian cancer are still unclear. Our study therefore firstly identified the expression profiles of necroptosis-related genes in normal and ovarian cancer tissues. Next, based on differentially expressed necroptosis-related genes, we clustered ovarian cancer patients into two subtypes and performed survival analysis. Subsequently, we constructed a risk model consisting of 5 genes by LASSO regression analysis based on the differentially expressed genes in the two subtypes, and confirmed the strong prognostic ability of the model and its potential as an independent risk factor via survival analysis and independent risk factor analysis. Based on this risk model, patients were divided into high and low risk groups. By exploring differentially expressed genes, enrichment functions and tumor immune microenvironment in patients in high and low risk groups, the results showed that patients in the low risk group were significantly enriched in immune signaling pathways. Besides, immune cells content, immune function activity was significantly better than the high-risk group. Eventually, we also investigated the sensitivity of patients with different risk groups to ICB immunotherapy and chemotherapy drugs. In conclusion, the risk model could effectively predict the survival and prognosis of patients, and explore the tumor microenvironment status of ovarian cancer patients to a certain extent, and provide promising and novel molecular markers for clinical diagnosis, individualized treatment and immunotherapy of patients.
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Affiliation(s)
- Zitao Wang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ganhong Chen
- Department of Pathology, The People's Hospital of Honghu, Honghu, Hubei, China
| | - Fangfang Dai
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shiyi Liu
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Hu
- Department of Obstetrics and Gynecology Ultrasound, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Wei Hu, ; Yanxiang Cheng,
| | - Yanxiang Cheng
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Wei Hu, ; Yanxiang Cheng,
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Understanding the Correlation between Metabolic Regulator SIRT1 and Exosomes with CA-125 in Ovarian Cancer: A Clinicopathological Study. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5346091. [PMID: 35496046 PMCID: PMC9053760 DOI: 10.1155/2022/5346091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 03/10/2022] [Indexed: 12/24/2022]
Abstract
Background Ovarian cancer (OvCa), the deadliest gynaecological malignancy, is associated with poor prognosis and high mortality rate. Ovarian cancer has been related with CA-125 and metabolic reprogramming by SIRT1 leading to metastasis with the involvement of exosomes. Methods Clinicopathological data of OvCa patients were collected to perform the analysis. Patients' samples were collected during surgery for immunohistochemistry and flow cytometric analysis of SIRT1, HIF-1α, exosomal markers (CD81 and CD63), ki-67, and PAS staining for glycogen deposition. Adjacent normal and tumor tissues were collected as per the CA-125 levels. Results CA-125, a vital diagnostic marker, has shown significant correlation with body mass index (BMI) (P = 0.0153), tumor type (P = 0.0029), ascites level, ascites malignancy, degree of dissemination, tumor differentiation, FIGO stage, TNM stage, laterality, and tumor size at P < 0.0001. Since significant correlation was associated with BMI and degree of dissemination, as disclosed by IHC analysis, metabolic marker SIRT1 (P = 0.0003), HIF-1α (P < 0.0001), exosomal marker CD81 (P < 0.0001), ki-67 status (P = 0.0034), and glycogen deposition (P <0.0001) were expressed more in tumor tissues as compared to the normal ones. ROC analysis of CA-125 had shown 327.7 U/ml has the best cutoff point with 82.4% sensitivity and specificity of 52.3%. In addition, Kaplan-Meier plots of CA-125 (P < 0.0001), BMI (P = 0.001), degree of dissemination (P < 0.0001), and ascites level (P <0.0001) reflected significant correlation with overall survival (OS). Upon multivariate Cox-regression analysis for overall survival (OS), BMI (P = 0.008, HR 1.759, 95% CI 1.156-2.677), ascites malignancy (P = 0.032, HR 0.336, 95% CI 0.124-0.911), and degree of dissemination (P = 0.004, HR 1.994, 95% CI 1.251-3.178) were significant proving to be independent indicators of the disease. Conclusion Clinicopathological parameters like BMI, degree of dissemination, and ascites level along with CA-125 can be prognostic factors for the disease. Levels of CA-125 can depict the metabolic and metastatic factors. Thus, by targeting SIRT1 and assessing exosomal concentrations to overcome metastasis and glycogen deposition, individualized treatment strategy could be designed. In-depth studies are still required.
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Sethi A, Kumar L, Mathur S, Mahey R, Kachhawa G, Bhatla N. Prognostic Significance of HE4 Tissue Expression in Serous Epithelial Ovarian Carcinoma. South Asian J Cancer 2022; 11:125-132. [DOI: 10.1055/s-0042-1742711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Background Human Epididymis protein 4 (HE4) is expressed in ovarian cancer. Preoperative serum testing is still not widely available. This pilot study aimed to investigate the magnitude of expression of HE4 in tissue sections of serous epithelial ovarian carcinoma, its correlation with clinical outcome, and the feasibility of HE4 immunohistochemistry as a prognostic marker.
Materials and Method In this ambispective study, immunohistochemistry (IHC) was used to evaluate tissue sections of ovarian serous epithelial carcinoma at primary cytoreductive surgery. On HE4 immunohistochemistry (IHC), the magnitude of HE4 expression was assessed categorically as high or low HE4 expression and semiquantitatively by the H-score, and correlated with clinical outcome in terms of survival status, progression-free survival, and overall survival.
Results Of 32 cases, most (n = 31, 96.8%) were positive for HE4 IHC. The mean age was 49 ± 8.2 years; 29 (90.6%) patients were in FIGO stage IIIC; 25 (78.9%) had ≥1cm residual disease after surgery; 31 (96.8%) received adjuvant chemotherapy, either 3-weekly (n = 25, 81.2%) or dose-dense weekly (n = 6, 18.8%) regimen. The majority (n = 31, 96.8%) had a high-grade tumor, of whom 19 (59.4%) had high HE4 expression and 13(40.6%) patients had H-score in the range of 5 to 8. The mean H-score was 6.97 ± 3.61 (range 0 to 12). The overall survival of the study population at 64 months was 36.65% (95% CI: 8.59–66.34), with median overall survival of 59 months. A new scoring system was developed combining categorical HE4 expression and serum CA-125 levels; the combination of HE4 expression with postoperative CA-125 levels was found to be the best prognostic marker for overall survival (p = 0.05). A composite score of 2 identified patients with poor progression-free survival (HR 4.64, p = 0.039) and overall survival (HR 5.45, p = 0.05).
Conclusion The new composite scoring system using HE4 IHC with postoperative serum CA-125 levels offers an extremely useful option for prognosticating patients with serous epithelial ovarian carcinoma than serum CA-125 alone. This is useful where preoperative records are not available to the treating clinician.
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Affiliation(s)
- Ankita Sethi
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Lalit Kumar
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mathur
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Reeta Mahey
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Garima Kachhawa
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Neerja Bhatla
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
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Piatek S, Panek G, Lewandowski Z, Piatek D, Kosinski P, Bidzinski M. Nadir CA-125 has prognostic value for recurrence, but not for survival in patients with ovarian cancer. Sci Rep 2021; 11:18190. [PMID: 34521891 PMCID: PMC8440776 DOI: 10.1038/s41598-021-97564-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 08/20/2021] [Indexed: 11/09/2022] Open
Abstract
The objective of this study was to evaluate the nadir CA-125 in patients with epithelial ovarian cancer. A total of 168 patients who achieved complete remission (no clinical and radiological signs, CA-125 ≤ 35 U/ml) after first-line treatment were enrolled in the study. The relationship between CA-125 and survival was examined by applying generalized additive models to the Cox proportional hazards model. The median CA-125 concentration after the treatment was 10 U/ml (2.7–35 U/ml). The nadir CA-125 was related to progression-free survival but not to overall survival. The risk of recurrence in patients with 11–25 U/ml and 26–35 U/ml compared to patients with ≤ 10 U/ml was 1.87 (p < 0.0024) and 2.17 (p < 0.018), respectively. An increased risk of recurrence according to the nadir CA-125 (≤ 10 U/ml vs. 11–25 U/ml and ≤ 10 U/ml vs. 26–35 U/ml) was found in patients with high-grade tumours (hazard ratio, HR = 2.08 and 2.59, respectively), advanced disease (HR = 2.38 and 2.03, respectively), serous histology (HR = 2.08 and 2.43, respectively) and after complete cytoreduction (HR = 2.7 and 2.72, respectively). No correlation between the CA-125 nadir and recurrence risk was found in patients with early-stage disease or those receiving neoadjuvant chemotherapy or bevacizumab.
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Affiliation(s)
- Szymon Piatek
- Department of Gynecologic Oncology, The Maria Sklodowska-Curie National Research Institute Of Oncology, Roentgen Street 5, 02-781, Warsaw, Poland.
| | - Grzegorz Panek
- 1St Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Zbigniew Lewandowski
- Department of Epidemiology and Biostatistics, Medical University of Warsaw, Warsaw, Poland
| | - Dominika Piatek
- 1St Department of Radiology, Medical University of Warsaw, Warsaw, Poland
| | - Przemyslaw Kosinski
- 1St Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Mariusz Bidzinski
- Department of Gynecologic Oncology, The Maria Sklodowska-Curie National Research Institute Of Oncology, Roentgen Street 5, 02-781, Warsaw, Poland
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Ye Y, Dai Q, Li S, He J, Qi H. A Novel Defined Risk Signature of the Ferroptosis-Related Genes for Predicting the Prognosis of Ovarian Cancer. Front Mol Biosci 2021; 8:645845. [PMID: 33869286 PMCID: PMC8047312 DOI: 10.3389/fmolb.2021.645845] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 03/09/2021] [Indexed: 01/10/2023] Open
Abstract
Ferroptosis is an iron-dependent, regulated form of cell death, and the process is complex, consisting of a variety of metabolites and biological molecules. Ovarian cancer (OC) is a highly malignant gynecologic tumor with a poor survival rate. However, the predictive role of ferroptosis-related genes in ovarian cancer prognosis remains unknown. In this study, we demonstrated that the 57 ferroptosis-related genes were expressed differently between ovarian cancer and normal ovarian tissue, and based on these genes, all OC cases can be well divided into 2 subgroups by applying consensus clustering. We utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to develop a multigene risk signature from the TCGA cohort and then validated it in an OC cohort from the GEO database. A 5-gene signature was built and reveals a favorable predictive efficacy in both TCGA and GEO cohort (P < 0.001 and P = 0.03). The GO and KEGG analysis revealed that the differentially expressed genes (DEGs) between the low- and high-risk subgroup divided by our risk model were associated with tumor immunity, and lower immune status in the high-risk group was discovered. In conclusion, ferroptosis-related genes are vital factors predicting the prognosis of OC and could be a novel potential treatment target.
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Affiliation(s)
- Ying Ye
- The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, China
| | - Qinjin Dai
- Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Shuhong Li
- The Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jie He
- The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, China
| | - Hongbo Qi
- The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, China
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