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Li T, Hou N, Mao L, Liu F, Ma Z, Wang L, Xu X, Yan G, Han Y, Wei J. Tumor Markers in Differential Diagnosis of Benign Ovarian Masses. Int J Womens Health 2024; 16:1517-1531. [PMID: 39309199 PMCID: PMC11414758 DOI: 10.2147/ijwh.s471058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 09/02/2024] [Indexed: 09/25/2024] Open
Abstract
Background Although there are many benign tumors in the ovarian adnexal area, the four most common types are still luteal cyst, ovarian mature cystic teratoma (OMCT), ovarian endometriosis, and benign epithelial tumors of the ovary. Purpose This study aimed to examine the correlation between six tumor markers (CEA, AFP, CA125, CA19-9, SCC, HE4) in the differential diagnosis of female adnexal benign masses and assess their diagnostic value. Patients and Methods In this study, 135 patients with adnexal benign masses were treated in Zhengzhou first people's Hospital from January 2018 to January 2023. 135 patients were divided into four groups: luteal cyst (13.3%), OMCT (42.2%), ovarian endometriosis (23.7%) and benign epithelial tumors of the ovary (including mucinous cystadenoma and serous cystadenoma) in group D. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of each marker and combined detection. Results The diameter of luteal cysts was significantly smaller than that of benign ovarian tumors (p < 0.001). ROC analysis showed that the combination of AFP, CA125, CA19-9, and SCC had a higher diagnostic rate for luteal cysts (AUC=0.871; sensitivity: 71.8%; specificity: 88.9). The SCC level in OMCT was significantly higher than in other benign ovarian tumors (p=0.007). ROC analysis indicated that the combination of AFP, HE4, and SCC had a higher diagnostic rate for OMCT (AUC=0.753; sensitivity: 65.4%; specificity: 75.4%). The CA125 level in ovarian endometriosis was significantly higher than in other accessory benign tumors (p < 0.001). ROC analysis demonstrated that the combination of AFP, CA125, and CA19-9 had a higher diagnostic rate for ovarian endometriosis (AUC=0.935; sensitivity: 76.7%; specificity: 96.9%). The tumor diameter of benign epithelial tumors of the ovary was significantly larger than that of other benign ovarian tumors (p < 0.001). ROC analysis revealed that the combination of CA125 and CA19-9 had a higher diagnostic rate for benign epithelial tumors of the ovary (AUC=0.792; sensitivity: 64.5%; specificity: 85.7%). Conclusion The findings of this study demonstrate that the combined use of tumor markers (CEA, AFP, CA125, CA19-9, SCC, and HE4) has value in diagnosing benign ovarian tumors, including luteal cysts, OMCT, ovarian endometriosis, and benign epithelial tumors of the ovary. However, it is important to acknowledge the limitations of this study, which include its single-center nature and the small sample size. Despite these limitations, the results highlight the potential utility of these markers in clinical practice.
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Affiliation(s)
- Tianlong Li
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Nana Hou
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Lili Mao
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Fangmei Liu
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Zilong Ma
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Li Wang
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Xiyue Xu
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Guanghui Yan
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Yujia Han
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
| | - Jinxian Wei
- Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China
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Ali MA, Sweed MS, NasrElDin EA, Ahmed WE, ElHawwary GE. Risk of Ovarian Malignancy Algorithm and Pelvic Mass Score for the prediction of malignant ovarian tumors: a prospective comparative study. J Ultrason 2024; 24:1-8. [PMID: 38343788 PMCID: PMC10850940 DOI: 10.15557/jou.2024.0001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 11/21/2022] [Indexed: 04/26/2024] Open
Abstract
Aim Ovarian cancer is the seventh most common female cancer worldwide. Nevertheless, there is no available universal screening method for malignant ovarian masses. This study compares the value of the Risk of Ovarian Malignancy Algorithm (ROMA) and Pelvic Mass Score (PMS) scoring systems in the diagnosis of malignant ovarian masses. Material and methods This prospective comparative study was conducted from March 2021 until April 2022. A total of 258 women diagnosed with ovarian mass and eligible for surgical intervention according to institutional guidelines were enrolled in the study. Ultrasound was performed for the assessment of masses, ascites and metastases, also color flow Doppler was done to measure the resistance index of the mass vasculature. Preoperative venous blood samples were collected to measure CA 125 and HE4. PMS and ROMA scoring systems were calculated for each patient. All women were subjected to a surgical intervention (according to applicable institutional guidelines), using either open or laparoscopic techniques. Histopathological examination of the removed specimens was done, and in line with the recognized gold standard, the results were compared with the pre-operative diagnosis of both scoring systems. Results Both PMS and ROMA showed a high predictive probability for ovarian malignancies (AUC = 0.93, sensitivity = 83.3%, specificity = 90.37%; AUC = 0.91, sensitivity = 84.4%, specificity = 95.56%, respectively), yet no statistical significant difference was found between the two scoring systems (p = 0.353, 95% CI -0.025 to 0.070). Conclusions Both PMS and ROMA seem to be promising scoring systems for discriminating benign from malignant ovarian masses, but more research is needed to determine the optimum diagnostic pathway, especially one yielding the least false-negative results.
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Affiliation(s)
- Mohamed A. Ali
- Department of Obstetrics and Gynecology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed S. Sweed
- Department of Obstetrics and Gynecology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Eman A. NasrElDin
- Department of Radiodiagnosis, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Walaa E. Ahmed
- Department of Obstetrics and Gynecology, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Gihan E. ElHawwary
- Department of Obstetrics and Gynecology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Abdoli N, Zhang K, Gilley P, Chen X, Sadri Y, Thai T, Dockery L, Moore K, Mannel R, Qiu Y. Evaluating the Effectiveness of 2D and 3D CT Image Features for Predicting Tumor Response to Chemotherapy. Bioengineering (Basel) 2023; 10:1334. [PMID: 38002458 PMCID: PMC10669238 DOI: 10.3390/bioengineering10111334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Background and Objective: 2D and 3D tumor features are widely used in a variety of medical image analysis tasks. However, for chemotherapy response prediction, the effectiveness between different kinds of 2D and 3D features are not comprehensively assessed, especially in ovarian-cancer-related applications. This investigation aims to accomplish such a comprehensive evaluation. Methods: For this purpose, CT images were collected retrospectively from 188 advanced-stage ovarian cancer patients. All the metastatic tumors that occurred in each patient were segmented and then processed by a set of six filters. Next, three categories of features, namely geometric, density, and texture features, were calculated from both the filtered results and the original segmented tumors, generating a total of 1403 and 1595 features for the 2D and 3D tumors, respectively. In addition to the conventional single-slice 2D and full-volume 3D tumor features, we also computed the incomplete-3D tumor features, which were achieved by sequentially adding one individual CT slice and calculating the corresponding features. Support vector machine (SVM)-based prediction models were developed and optimized for each feature set. Five-fold cross-validation was used to assess the performance of each individual model. Results: The results show that the 2D feature-based model achieved an AUC (area under the ROC curve (receiver operating characteristic)) of 0.84 ± 0.02. When adding more slices, the AUC first increased to reach the maximum and then gradually decreased to 0.86 ± 0.02. The maximum AUC was yielded when adding two adjacent slices, with a value of 0.91 ± 0.01. Conclusions: This initial result provides meaningful information for optimizing machine learning-based decision-making support tools in the future.
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Affiliation(s)
- Neman Abdoli
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (N.A.); (K.Z.); (Y.S.)
| | - Ke Zhang
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (N.A.); (K.Z.); (Y.S.)
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA
| | - Patrik Gilley
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (N.A.); (K.Z.); (Y.S.)
| | - Xuxin Chen
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (N.A.); (K.Z.); (Y.S.)
| | - Youkabed Sadri
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (N.A.); (K.Z.); (Y.S.)
| | - Theresa Thai
- Department of Radiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Lauren Dockery
- Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Kathleen Moore
- Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Robert Mannel
- Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Yuchen Qiu
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (N.A.); (K.Z.); (Y.S.)
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Niemira M, Erol A, Bielska A, Zeller A, Skwarska A, Chwialkowska K, Kuzmicki M, Szamatowicz J, Reszec J, Knapp P, Moniuszko M, Kretowski A. Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer. Sci Rep 2023; 13:19287. [PMID: 37935712 PMCID: PMC10630404 DOI: 10.1038/s41598-023-45317-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/18/2023] [Indexed: 11/09/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.
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Affiliation(s)
- Magdalena Niemira
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
| | - Anna Erol
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Agnieszka Bielska
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Anna Zeller
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Anna Skwarska
- Cancer Center, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Karolina Chwialkowska
- Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, Bialystok, Poland
| | - Mariusz Kuzmicki
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Jacek Szamatowicz
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Joanna Reszec
- Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland
| | - Pawel Knapp
- University Oncology Centre, University Clinical Hospital in Bialystok, Bialystok, Poland
| | - Marcin Moniuszko
- Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland
| | - Adam Kretowski
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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Ma J, Chen Y, Ren J, Zhou T, Wang Z, Li C, Qiu L, Gao T, Ding P, Ding Z, Ou L, Wang J, Xu J, Zhou Z, Jia C, Sun N, Pei R, Zhu W. Purification of Circulating Tumor Cells Based on Multiantibody-Modified Magnetic Nanoparticles and Molecular Analysis toward Epithelial Ovarian Cancer Detection. ACS Sens 2023; 8:3744-3753. [PMID: 37773014 DOI: 10.1021/acssensors.3c01063] [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] [Indexed: 09/30/2023]
Abstract
Circulating tumor cells (CTCs) are valuable circulating biomarkers of cancer, which carry primary tumor information and may provide real-time assessment of tumor status as well as treatment response in cancer patients. Herein, we developed a novel assay for accurate diagnosis and dynamic monitoring of epithelial ovarian cancer (EOC) using CTC RNA analysis. Multiantibody-modified magnetic nanoparticles were prepared for purification of EOC CTCs from whole blood samples of clinical patients. Subsequently, nine EOC-specific mRNAs of purified CTCs were quantified using droplet digital PCR. The EOC CTC Score was generated using a multivariate logistic regression model for each sample based on the transcripts of the nine genes. This assay exhibited a distinguishing diagnostic performance for the detection of EOC (n = 17) from benign ovarian tumors (n = 30), with an area under the receiver operating characteristic curve (AUC) of 0.96 (95% CI = 0.91-1.00). Moreover, dynamic changes of the EOC CTC Score were observed in patients undergoing treatment, demonstrating the potential of the assay for monitoring EOC. In conclusion, we present an accurate assay for the diagnosis and monitoring of EOC via CTC RNA analysis, and the results suggest that it may provide a promising solution for the detection and treatment response assessment of EOC.
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Affiliation(s)
- Jialing Ma
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Ying Chen
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Jing Ren
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Tongping Zhou
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Zhili Wang
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Cheng Li
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Lei Qiu
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
- Department of Chemistry, College of Sciences, Shanghai University, Shanghai 200444, China
| | - Tian Gao
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Pi Ding
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
| | - Zixin Ding
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
- State Key Laboratory of Natural Medicines, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, China
| | - Li Ou
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Jun Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Jinni Xu
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Zhirun Zhou
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Chenxin Jia
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Na Sun
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
| | - Renjun Pei
- CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China
| | - Weipei Zhu
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
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Trinidad CV, Pathak HB, Cheng S, Tzeng SC, Madan R, Sardiu ME, Bantis LE, Deighan C, Jewell A, Rayamajhi S, Zeng Y, Godwin AK. Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer. Sci Rep 2023; 13:18341. [PMID: 37884576 PMCID: PMC10603107 DOI: 10.1038/s41598-023-44050-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 10/03/2023] [Indexed: 10/28/2023] Open
Abstract
High grade serous ovarian carcinoma (HGSOC) accounts for ~ 70% of ovarian cancer cases. Non-invasive, highly specific blood-based tests for pre-symptomatic screening in women are crucial to reducing the mortality associated with this disease. Since most HGSOCs typically arise from the fallopian tubes (FT), our biomarker search focused on proteins found on the surface of extracellular vesicles (EVs) released by both FT and HGSOC tissue explants and representative cell lines. Using mass spectrometry, 985 EV proteins (exo-proteins) were identified that comprised the FT/HGSOC EV core proteome. Transmembrane exo-proteins were prioritized because these could serve as antigens for capture and/or detection. With a nano-engineered microfluidic platform, six newly discovered exo-proteins (ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF) plus a known HGSOC associated protein, FOLR1 exhibited classification performance ranging from 85 to 98% in a case-control study using plasma samples representative of early (including stage IA/B) and late stage (stage III) HGSOCs. Furthermore, by a linear combination of IGSF8 and ITGA5 based on logistic regression analysis, we achieved a sensitivity of 80% with 99.8% specificity and a positive predictive value of 13.8%. Importantly, these exo-proteins also can accurately discriminate between ovarian and 12 types of cancers commonly diagnosed in women. Our studies demonstrate that these lineage-associated exo-biomarkers can detect ovarian cancer with high specificity and sensitivity early and potentially while localized to the FT when patient outcomes are more favorable.
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Affiliation(s)
- Camille V Trinidad
- Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS, USA
| | - Harsh B Pathak
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 3040, Kansas City, KS, 66160, USA
- University of Kansas Cancer Center, Kansas City, KS, USA
- Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Shibo Cheng
- Department of Chemistry, University of Florida, Gainesville, FL, USA
| | | | - Rashna Madan
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 3040, Kansas City, KS, 66160, USA
| | - Mihaela E Sardiu
- University of Kansas Cancer Center, Kansas City, KS, USA
- Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA
- Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, USA
| | - Leonidas E Bantis
- University of Kansas Cancer Center, Kansas City, KS, USA
- Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA
- Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, USA
| | | | - Andrea Jewell
- University of Kansas Cancer Center, Kansas City, KS, USA
- Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS, USA
| | - Sagar Rayamajhi
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 3040, Kansas City, KS, 66160, USA
| | - Yong Zeng
- Department of Chemistry, University of Florida, Gainesville, FL, USA
| | - Andrew K Godwin
- Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS, USA.
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 3040, Kansas City, KS, 66160, USA.
- University of Kansas Cancer Center, Kansas City, KS, USA.
- Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
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Song J, Sokoll LJ, Zhang Z, Chan DW. VCAM-1 complements CA-125 in detecting recurrent ovarian cancer. Clin Proteomics 2023; 20:25. [PMID: 37357306 PMCID: PMC10291808 DOI: 10.1186/s12014-023-09414-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 06/13/2023] [Indexed: 06/27/2023] Open
Abstract
BACKGROUND Close to three-quarters of ovarian cancer cases are frequently diagnosed at an advanced stage, with more than 70% of them failing to respond to primary therapy and relapsing within 5 years. There is an urgent need to identify strategies for early detection of ovarian cancer recurrence, which may lead to earlier intervention and better outcomes. METHODS A customized magnetic bead-based 8-plex immunoassay was evaluated using a Bio-Plex 200 Suspension Array System. Target protein levels were analyzed in sera from 58 patients diagnosed with advanced ovarian cancer (including 34 primary and 24 recurrent tumors) and 46 healthy controls. The clinical performance of these biomarkers was evaluated individually and in combination for their ability to detect recurrent ovarian cancer. RESULTS An 8-plex immunoassay was evaluated with high analytical performance suitable for biomarker validation studies. Logistic regression modeling selected a two-marker panel of CA-125 and VCAM-1 that improved the performance of CA-125 alone in detecting recurrent ovarian cancer (AUC: 0.813 versus 0.700). At a fixed specificity of 83%, the two-marker panel significantly improved sensitivity in separating primary from recurrent tumors (70.8% versus 37.5%, P = 0.004), demonstrating that VCAM-1 was significantly complementary to CA-125 in detecting recurrent ovarian cancer. CONCLUSIONS A two-marker panel of CA-125 and VCAM-1 showed strong diagnostic performance and improvement over the use of CA-125 alone in detecting recurrent ovarian cancer. The experimental results warrant further clinical validation to determine their role in the early detection of recurrent ovarian cancer.
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Affiliation(s)
- Jin Song
- Center for Biomarker Discovery and Translation, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- Department of Pathology, Johns Hopkins University School of Medicine, 419 North Caroline Street, Baltimore, MD, 21231, USA.
| | - Lori J Sokoll
- Center for Biomarker Discovery and Translation, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Zhen Zhang
- Center for Biomarker Discovery and Translation, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Daniel W Chan
- Center for Biomarker Discovery and Translation, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
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Anbarasu S, Anbarasu A. Cancer-biomarkers associated with sex hormone receptors and recent therapeutic advancements: a comprehensive review. Med Oncol 2023; 40:171. [PMID: 37162589 DOI: 10.1007/s12032-023-02044-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 05/02/2023] [Indexed: 05/11/2023]
Abstract
Hormones and its regulation plays vital role in causing breast, prostate, ovarian and endometrial cancers collectively known as hormone-sensitive cancers. This review discusses the various functions of the sex hormones and the biological pathways involved in causing hormone-associated cancer under differential regulation. We have also attempted to explore the biomarkers associated with the cancers and the current therapeutic availability to treat such cancers. Among various sex hormones such as estrogen, progesterone and androgen, estrogen the female sex hormone and its receptor had a major contribution in causing cancer and hence are considered a predominant target in treating the associated cancers. Other hormones and receptors such a androgen, progesterone, and their respective receptors were also reported to have a significant correlation in causing cancers. Apart from these receptors certain enzymes that act as precursors or as promoters are also targeted for treatment strategies. The drugs commonly used belong to the selective drug classes such as selective estrogen receptor modulators and selective progesterone receptor modulators. In the case of androgen regulation androgen deprivation therapies are practiced. It is also suggested that the use of natural substances to treat cancer could prevent resistance and reduce side effects. Identification of significant targets and the discovery of many efficient drugs shall be possible in the future with better understanding of hormone regulation and its influence on cancer causative mechanisms.
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Affiliation(s)
- Suvitha Anbarasu
- Medical and Biological Computing Laboratory, Department of Biotechnology, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Anand Anbarasu
- Medical and Biological Computing Laboratory, Department of Biotechnology, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
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9
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Trinidad C, Pathak H, Cheng S, Tzeng SC, Madan R, Sardiu M, Bantis L, Deighan C, Jewell A, Zeng Y, Godwin A. Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer. RESEARCH SQUARE 2023:rs.3.rs-2814022. [PMID: 37205573 PMCID: PMC10187430 DOI: 10.21203/rs.3.rs-2814022/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
High grade serous ovarian carcinoma (HGSOC) accounts for ~ 70% of ovarian cancer cases. Non-invasive, highly specific blood-based tests for pre-symptomatic screening in women are crucial to reducing the mortality associated with this disease. Since most HGSOCs typically arise from the fallopian tubes (FT), our biomarker search focused on proteins found on the surface of extracellular vesicles (EVs) released by both FT and HGSOC tissue explants and representative cell lines. Using mass spectrometry, 985 EV proteins (exo-proteins) were identified that comprised the FT/HGSOC EV core proteome. Transmembrane exo-proteins were prioritized because these could serve as antigens for capture and/or detection. With a nano-engineered microfluidic platform, six newly discovered exo-proteins (ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF) plus a known HGSOC associated protein, FOLR1 exhibited classification performance ranging from 85-98% in a case-control study using plasma samples representative of early (including stage IA/B) and late stage (stage III) HGSOCs. Furthermore, by linear combination of IGSF8 and ITGA5 based on logistic regression analysis, we achieved a sensitivity of 80% (99.8% specificity). These lineage-associated exo-biomarkers have potential to detect cancer while localized to the FT when patient outcomes are more favorable.
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10
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Diagnostics of Ovarian Tumors in Postmenopausal Patients. Diagnostics (Basel) 2022; 12:diagnostics12112619. [DOI: 10.3390/diagnostics12112619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 10/16/2022] [Accepted: 10/17/2022] [Indexed: 11/16/2022] Open
Abstract
Early diagnosis of ovarian cancer remains an urgent issue owing to the continuing trend towards increasing incidence along with only marginal improvements in mortality and 5-year survival rates. Furthermore, there is a lack of a clear formulation of the concept of pathogenesis. The diagnostic values of tumor markers, their potential advantages and disadvantages, and their combination with radiation imaging methods and transvaginal sonography are discussed. More advanced imaging techniques, such as computed tomography and magnetic resonance imaging have proven too expensive for widespread use. According to the World Health Organization, more than half of the world’s population does not have access to diagnostic imaging. Consequently, there is high demand for a low-cost, reliable, and safe imaging system for detecting and monitoring cancer. Currently, there is no clear algorithm available for examining and accurately diagnosing patients with postmenopausal ovarian tumors; moreover, reliable criteria allowing dynamic observation and for determining surgical access and optimal surgical intervention measures in postmenopausal patients are lacking. Medical microwave radiometry shows promising results yielding an accuracy of 90%.
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11
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Keshavarz A, Salehi A, Khosravi S, Shariati Y, Nasrabadi N, Kahrizi MS, Maghsoodi S, Mardi A, Azizi R, Jamali S, Fotovat F. Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies. Stem Cell Res Ther 2022; 13:482. [PMID: 36153626 PMCID: PMC9509604 DOI: 10.1186/s13287-022-03163-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 08/12/2022] [Indexed: 11/10/2022] Open
Abstract
Advancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years.
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Affiliation(s)
- Ali Keshavarz
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Salehi
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Islamic Azad University,, Isfahan (Khorasgan) Branch, Isfahan, Iran
| | - Setareh Khosravi
- Department of Orthodontics, School of Dentistry, Alborz University of Medical Sciences, Karaj, Iran
| | - Yasaman Shariati
- Department of General Surgery, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Navid Nasrabadi
- Department of Endodontics, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
| | | | - Sairan Maghsoodi
- Department of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Amirhossein Mardi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ramyar Azizi
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samira Jamali
- Department of Endodontics, College of Stomatology, Stomatological Hospital, Xi’an Jiaotong University, Shaanxi, People’s Republic of China
| | - Farnoush Fotovat
- Department of Prosthodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
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12
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Huwidi A, Abobrege A, Assidi M, Buhmeida A, Ermiah E. Diagnostic value of risk of malignancy index in the clinical evaluation of ovarian mass. Mol Clin Oncol 2022; 17:118. [PMID: 35747594 PMCID: PMC9204318 DOI: 10.3892/mco.2022.2551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/15/2021] [Indexed: 11/23/2022] Open
Abstract
In the present study, the Risk Malignancy Index (RMI) was calculated based on menopausal status, ultrasound (US) findings and serum biological cancer antigen 125 (CA-125) levels as a scoring system in Libyan females with ovarian masses (OMs) to differentiate between benign and malignant tumors. A total of 51 females with OMs referred to the Gynaecology Department of the National Cancer Institute in Misurata (Libya) between January 2019 and December 2020 were retrospectively reviewed for diagnostic testing. Clinicopathological and demographic data were obtained from patient records. A cut-off point of RMI=200 was used to differentiate between benign and malignant tumors. The mean age of the patients was 47 years (range, 19-90 years) and 60% of the patients were premenopausal. Examination of the four RMI indices and disease status indicated that the association with the US score (P<0.0001) and with CA-125 (P=0.017) was highly significant. However, the age at diagnosis and menopausal status did not have any significant association with the disease status. The RMI with a cut-off point of 200 had a sensitivity and specificity of 87.5 and 90.7%, respectively, and a positive and negative predictive value of 63.6 and 97.5%, respectively. The association between the RMI and disease status was highly significant (P<0.0001). In conclusion, the RMI appears to be a reliable, simple and cost-effective tool for clinical differentiation between benign and malignant OMs. This may help to improve the optimal diagnosis and planning of an individualized treatment strategy. However, given the small sample size of the cohort, further validation using larger cohorts in other settings is recommended.
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Affiliation(s)
- Ali Huwidi
- Department of Gynaecology, National Cancer Institute, Misurata University, Misurata 051, Libya
| | - Afaf Abobrege
- Department of Gynaecology, National Cancer Institute, Misurata University, Misurata 051, Libya
| | - Mourad Assidi
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Makkah 21589, Saudi Arabia
| | - Abdelbaset Buhmeida
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Makkah 21589, Saudi Arabia
| | - Eramah Ermiah
- Medical Research Unit, National Cancer Institute, Misurata 051, Libya
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13
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Wu M, Liu S, Qi F, Qiu R, Feng J, Ren X, Rong S, Ma H, Chang D, Pan H. A label-free electrochemical immunosensor for CA125 detection based on CMK-3(Au/Fc@MgAl-LDH)n multilayer nanocomposites modification. Talanta 2022; 241:123254. [DOI: 10.1016/j.talanta.2022.123254] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/13/2022] [Accepted: 01/20/2022] [Indexed: 01/31/2023]
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14
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Kumarasamy G, Kaur G. Protein biomarkers in gynecological cancers: The need for translational research towards clinical applications. CLINICA E INVESTIGACION EN GINECOLOGIA Y OBSTETRICIA 2022. [DOI: 10.1016/j.gine.2021.100735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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15
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Janjua KA, Shahzad R, Shehzad A. Development of Novel Cancer Biomarkers for Diagnosis and Prognosis. CANCER BIOMARKERS IN DIAGNOSIS AND THERAPEUTICS 2022:277-343. [DOI: 10.1007/978-981-16-5759-7_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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16
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rGO based immunosensor amplified using MWCNT and CNF nanocomposite as analytical tool for CA125 detection. Anal Biochem 2021; 634:114393. [PMID: 34597616 DOI: 10.1016/j.ab.2021.114393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/04/2021] [Accepted: 09/25/2021] [Indexed: 11/24/2022]
Abstract
The electrochemical performance of dual layer immunosensor has been studied by employing reduced Graphene oxide (rGO) and its nanocomposites with Carbon Nanofibers (CNFs) and Carbon Nanotubes (CNTs) as supporting matrix for the detection of CA125. The immunosensor determination was based on the formation of antibody - antigen immunocomplex, a decrement in the current response was observed in accordance with the concentration of antigen. Better performance exhibited by rGO/CNF in terms of linearity (99%) and sensitivity 0.65 μA (μg mL-1)-1 can be attributed to its conductivity and surface area. The nanocomposite are employed in the detection of CA125 with linear working range of 10-32 × 10-4 μg mL-1, the limit of detection is found to be 0.28 pg mL-1 rGO nanocomposite with CNT (rGO/CNT) is studied as transducer material. rGO/CNT exhibited better linearity when compared to rGO due to its good conductivity. Thus, graphene nanocomposite transducer materials have vital application in detection of oncomarkers.
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17
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Vandghanooni S, Sanaat Z, Farahzadi R, Eskandani M, Omidian H, Omidi Y. Recent progress in the development of aptasensors for cancer diagnosis: Focusing on aptamers against cancer biomarkers. Microchem J 2021. [DOI: 10.1016/j.microc.2021.106640] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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18
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Yousefi M, Rajaie S, Keyvani V, Bolandi S, Hasanzadeh M, Pasdar A. Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy. Sci Rep 2021; 11:10524. [PMID: 34006887 PMCID: PMC8131620 DOI: 10.1038/s41598-021-88780-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 04/14/2021] [Indexed: 01/04/2023] Open
Abstract
Circulating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).
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Affiliation(s)
- Meysam Yousefi
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sara Rajaie
- Department of Biology, Islamic Azad University, Arsanjan Branch, Arsanjan, Iran
| | - Vahideh Keyvani
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Somayeh Bolandi
- Department of Gynecologic Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Malihe Hasanzadeh
- Department of Gynecologic Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Pasdar
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. .,Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. .,Division of Applied Medicine, Faculty of Medicine, University of Aberdeen, Foresterhill, Aberdeen, UK.
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19
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Noreen S, Akhtar S, Batool T, Gardner QA, Akhtar MW. Tubulin Beta 2C Chain (TBB2C), a Potential Marker of Ovarian Cancer, an Insight from Ovarian Cancer Proteome Profile. ACS OMEGA 2021; 6:10506-10514. [PMID: 34056205 PMCID: PMC8153795 DOI: 10.1021/acsomega.0c03262] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 11/23/2020] [Indexed: 06/12/2023]
Abstract
Ovarian cancer (OC) is the most lethal among female reproductive system malignancies. Depending upon the stage at presentation, the five year survival ratio varies from ∼92 to ∼30%. The role of biomarkers in early cancer diagnosis, including OC, is well understood. In our previous study, through an initial screening, we have analyzed eleven proteins that exhibited differential expression in OC using two-dimensional gel electrophoresis (2D-GE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometric (MALDI-TOF MS) analysis. In continuation of our previous study, the present work describes analysis of twenty more proteins that showed aberrant expression in OC. Among these, six showed consistent significant deregulation in the OC false discovery rate [FDR ≤ 0.05]. Upon MS analysis, they were identified as vimentin, tubulin beta 2C chain, tubulin alpha 1C chain, actin cytoplasmic 2, apolipoprotein A-I, and collagen alpha 2(VI) chain [peptide mass fingerprint (PMF) score ≥ 79]. One of the differentially regulated proteins, tubulin beta 2C chain, was found to be significantly (fold change, 2.5) enhanced in OC. Verification by western blot and enzyme-linked immunosorbent assay (ELISA) demonstrated that the tubulin beta 2C chain may serve as a valuable marker for OC (ANOVA p < 0.0001). The assessment of the likely association of TBB2C with OC in a larger population will not only help in developing clinically useful biomarkers in the future but also improve our understanding of the progression of OC disease.
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20
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Trinidad CV, Tetlow AL, Bantis LE, Godwin AK. Reducing Ovarian Cancer Mortality Through Early Detection: Approaches Using Circulating Biomarkers. Cancer Prev Res (Phila) 2021; 13:241-252. [PMID: 32132118 DOI: 10.1158/1940-6207.capr-19-0184] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/20/2019] [Accepted: 08/15/2019] [Indexed: 12/18/2022]
Abstract
More than two-thirds of all women diagnosed with epithelial ovarian cancer (EOC) will die from the disease (>14,000 deaths annually), a fact that has not changed considerably in the last three decades. Although the 5-year survival rates for most other solid tumors have improved steadily, ovarian cancer remains an exception, making it the deadliest of all gynecologic cancers and five times deadlier than breast cancer. When diagnosed early, treatment is more effective, with a 5-year survival rate of up to 90%. Unfortunately, most cases are not detected until after the cancer has spread, resulting in a dismal 5-year survival rate of less than 30%. Current screening methods for ovarian cancer typically use a combination of a pelvic examination, transvaginal ultrasonography, and serum cancer antigen 125 (CA125), but these have made minimal impact on improving mortality. Thus, there is a compelling unmet need to develop new molecular tools that can be used to diagnose early-stage EOC and/or assist in the clinical management of the disease after a diagnosis, given that more than 220,000 women are living with ovarian cancer in the United States and are at risk of recurrence. Here, we discuss the state of advancing liquid-based approaches for improving the early detection of ovarian cancer.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.
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Affiliation(s)
- Camille V Trinidad
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas
| | - Ashley L Tetlow
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas
| | - Leonidas E Bantis
- Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas
| | - Andrew K Godwin
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas. .,The University of Kansas Cancer Center, Kansas City, Kansas
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21
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Ali MN, Habib D, Hassanien AI, Abbas AM. Comparison of the four malignancy risk indices in the discrimination of malignant ovarian masses: A cross-sectional study. J Gynecol Obstet Hum Reprod 2020; 50:101986. [PMID: 33197624 DOI: 10.1016/j.jogoh.2020.101986] [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: 07/23/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To evaluate the accuracy of the four malignancy risk indices to distinguish benign from malignant ovarian masses MATERIALS AND METHODS: This was an observational cross-sectional study conducted on 155 patients between January 2016 and January 2019. Women with ovarian masses planned for surgical management were recruited from the outpatient Gynecology clinic of the hospital. The risk of malignancy index (RMI 1-4) was calculated for all women with ovarian masses. Biopsies obtained from the ovarian masses after the surgical intervention was sent to the pathology lab for histopathological examination. The histopathologic diagnosis of the ovarian masses was considered the gold standard for diagnosis. RESULTS The participants' mean age in the group of patients with benign masses was 33.50 ± 14.53 years versus 45.09 ± 13.67 years in the malignant group. The two most prominent features in the malignant group were solid areas in 85.3 % of malignant masses and about 91.2 % of malignant masses showing size <7 cm in their largest diameter. The RMI's most sensitive individual parameter was the CA-125 level, while the lowest sensitivity was for the menopausal status. RMI 2 had the highest sensitivity of 76.47 %, while RMI 1 and 3 had the highest specificity, 92.56 %. RMI 2 had the highest AUC, 0.83. CONCLUSIONS RMI 2 is a simple and reliable tool and had the best performance among all RMIs in benign discrimination from malignant ovarian masses with high sensitivity and accuracy.
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Affiliation(s)
- Mustafa N Ali
- Department of Obstetrics & Gynecology, Woman's Health Hospital, Faculty of Medicine, Assiut University, Egypt
| | - Dina Habib
- Department of Obstetrics & Gynecology, Woman's Health Hospital, Faculty of Medicine, Assiut University, Egypt
| | - Ahmed I Hassanien
- Department of Obstetrics & Gynecology, Woman's Health Hospital, Faculty of Medicine, Assiut University, Egypt
| | - Ahmed M Abbas
- Department of Obstetrics & Gynecology, Woman's Health Hospital, Faculty of Medicine, Assiut University, Egypt.
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22
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Kumar V, Gupta S, Varma K, Sachan M. MicroRNA as Biomarker in Ovarian Cancer Management: Advantages and Challenges. DNA Cell Biol 2020; 39:2103-2124. [PMID: 33156705 DOI: 10.1089/dna.2020.6024] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Ovarian cancer is the most prevalent gynecological malignancy affecting women throughout the globe. Ovarian cancer has several subtypes, including epithelial ovarian cancer (EOC) with a whopping incidence rate of 239,000 per year, making it the sixth most common gynecological malignancy worldwide. Despite advancement of detection and therapeutics, death rate accounts for 152,000 per annum. Several protein-based biomarkers such as CA125 and HE4 are currently being used for diagnosis, but their sensitivity and specificity for early detection of ovarian cancer are under question. MicroRNA (a small noncoding RNA molecule that participates in post-transcription regulation of gene expression) and its functional deregulation in most cancers have been discovered in the previous two decades. Studies support that miRNA deregulation has an epigenetic component as well. Aberrant miRNA expression is often correlated with the form of EOC tumor, histological grade, prognosis, and FIGO stage. In this review, we addressed epigenetic regulation of miRNAs, the latest research on miRs as a biomarker in the detection of EOC, and tailored assays to use miRNAs as a biomarker in ovarian cancer diagnosis.
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Affiliation(s)
- Vivek Kumar
- Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad, India
| | - Sameer Gupta
- Department of Surgical Oncology, King George Medical University, Lucknow, India
| | - Kachnar Varma
- Department of Pathology, Motilal Nehru Medical College, Allahabad, India
| | - Manisha Sachan
- Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad, India
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Gowthami J, Gururaj N, Mahalakshmi V, Sathya R, Sabarinath TR, Doss DM. Genetic predisposition and prediction protocol for epithelial neoplasms in disease-free individuals: A systematic review. J Oral Maxillofac Pathol 2020; 24:293-307. [PMID: 33456239 PMCID: PMC7802851 DOI: 10.4103/jomfp.jomfp_348_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 03/23/2020] [Accepted: 04/24/2020] [Indexed: 01/13/2023] Open
Abstract
Background Epithelial neoplasm is an important global health-care problem, with high morbidity and mortality rates. Early diagnosis and appropriate treatment are essential for increased life survival. Prediction of occurrence of malignancy in a disease-free individual by any means will be a great breakthrough for healthy living. Aims and Objectives The aims and objectives were to predict the genetic predisposition and propose a prediction protocol for epithelial malignancy of various systems in our body, in a disease-free individual. Methods We have searched databases both manually and electronically, published in English language in Cochrane group, Google search, MEDLINE and PubMed from 2000 to 2019. We have included all the published, peer-reviewed, narrative reviews; randomized controlled trials; case-control studies; and cohort studies and excluded the abstract-only articles and duplicates. Specific words such as "etiological factors," "pathology and mutations," "signs and symptoms," "genetics and IHC marker," and "treatment outcome" were used for the search. A total of 1032 citations were taken, and only 141 citations met the inclusion criteria and were analyzed. Results After analyzing various articles, the etiological factors, clinical signs and symptoms, genes and the pathology involved and the commonly used blood and tissue markers were analyzed. A basic investigation strategy using immunohistochemistry markers was established. Conclusion The set of proposed biomarkers should be studied in future to predict genetic predisposition in disease-free individuals.
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Affiliation(s)
- J Gowthami
- Department of Oral and Maxillofacial Pathology and Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - N Gururaj
- Department of Oral and Maxillofacial Pathology and Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - V Mahalakshmi
- Department of Oral and Maxillofacial Pathology and Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - R Sathya
- Department of Oral and Maxillofacial Pathology and Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - T R Sabarinath
- Department of Oral and Maxillofacial Pathology and Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Daffney Mano Doss
- Department of Oral and Maxillofacial Pathology and Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
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24
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Arayataweegool A, Srisuttee R, Bin-Alee F, Mahattanasakul P, Tangjaturonrasme N, Kerekhanjanarong V, Mutirangura A, Kitkumthorn N. Induction of ZCCHC6 expression in peripheral blood mononuclear cells by HNSCC secretions. Gene 2020; 754:144880. [PMID: 32526260 DOI: 10.1016/j.gene.2020.144880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/31/2020] [Accepted: 06/06/2020] [Indexed: 12/15/2022]
Abstract
Cancer secretion can change the properties of adjacent cells, including peripheral blood mononuclear cells (PBMCs). We investigated whether such secretion influences messenger RNA expression in PBMCs of patients with head and neck squamous cell carcinoma (HNSCC). In the present study, co-culture model of normal PBMCs and HNSCC cell lines were established. The PBMCs were subsequently subjected to RNA sequencing for transcriptome analysis. Furthermore, expression data from the Gene Expression Omnibus repository, platform GPL4133, series GSE39400, were gathered to analyze, afterward identify zinc finger CysCysHisCys (CCHC)-type domain-containing protein 6 (ZCCHC6) as the main gene involved in HNSCC. This gene was then validated by a quantitative real-time polymerase chain reaction. The results showed that ZCCHC6 was expressed at significantly higher levels in the patients with HNSCC than in the healthy controls, and the sensitivity and specificity of these findings for diagnostic purposes were 100.00% and 70.83%, respectively. In summary, our findings demonstrated that the secretion of HNSCC cells could cause the alterations in messenger RNA expression by PBMCs. The ZCCHC6 expression level may apply in HNSCC screening.
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Affiliation(s)
- Areeya Arayataweegool
- Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Ratakorn Srisuttee
- Faculty of Medicine, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand
| | - Fardeela Bin-Alee
- Program of Medical Science, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Patnarin Mahattanasakul
- Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Department of Otolaryngology, Head and Neck Surgery, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Napadon Tangjaturonrasme
- Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Virachai Kerekhanjanarong
- Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Apiwat Mutirangura
- Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Nakarin Kitkumthorn
- Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand.
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25
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Csibi N, Brubel R, Dobó N, Mészáros KV, Molvarec A, Lukovich P, Rigó J, Bokor AZ. Gamma-Synuclein Levels Are Elevated in Peritoneal Fluid of Patients with Endometriosis. Med Sci Monit 2020; 26:e922137. [PMID: 32393729 PMCID: PMC7243616 DOI: 10.12659/msm.922137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background The role of gamma-synuclein (SNCG) has been widely examined in malignant conditions due to its possible role in disease progression, but very little information is available on its theoretical function on endometriosis formation. Material/Methods Between January 2016 and December 2016, we collected peritoneal fluid and plasma samples from 45 consecutive female patients, of which 15 were without endometriosis, 15 had minimal to mild endometriosis, and 15 had moderate to severe endometriosis. The statistical power was 0.98. We evaluated SNCG levels in the peritoneal fluid and plasma of patients diagnosed with endometriosis, and we compared them with the levels obtained from disease-free control subjects by using enzyme-linked immunosorbent assay. Results SNCG levels were statistically significantly (1.2-fold) higher in the peritoneal fluid of patients with endometriosis compared to controls (p=0.04). We did not find a significant difference between SNCG levels in the plasma of our endometriosis patients and the control group (p=0.086). However, despite previous data showing very limited expression of SNCG in healthy tissues, we found SNCG in the peritoneal fluid of all of the patients in our healthy control group. Conclusions Levels of SNCG were statistically significantly higher in the peritoneal fluid of patients with endometriosis compared to disease-free controls, which may indicate its possible role the formation and progression of the disease. Moreover, its biological function should be further investigated due to the conflicting results concerning its expression in healthy tissues.
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Affiliation(s)
- Noémi Csibi
- Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
| | - Réka Brubel
- Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
| | - Noémi Dobó
- Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
| | - Katalin Viola Mészáros
- "Lendület" Hereditary Endocrine Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University (HAS-SE), Budapest, Hungary
| | - Attila Molvarec
- Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
| | - Péter Lukovich
- Department of Surgery, St. John Hospital, Budapest, Hungary
| | - János Rigó
- Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
| | - Attila Z Bokor
- Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
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26
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Aziz NB, Mahmudunnabi RG, Umer M, Sharma S, Rashid MA, Alhamhoom Y, Shim YB, Salomon C, Shiddiky MJA. MicroRNAs in ovarian cancer and recent advances in the development of microRNA-based biosensors. Analyst 2020; 145:2038-2057. [DOI: 10.1039/c9an02263e] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Ovarian cancer is the most aggressive of all gynaecological malignancies and is the leading cause of cancer-associated mortality worldwide.
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Affiliation(s)
- Nahian Binte Aziz
- School of Environment and Science
- Griffith University
- Nathan Campus
- Australia
- School of Chemistry & Molecular Biosciences
| | - Rabbee G. Mahmudunnabi
- Department of Molecular Science Technology and Institute of BioPhysio Sensor Technology (IBST)
- Pusan National University
- Busan 46241
- Republic of Korea
| | - Muhammad Umer
- Queensland Micro and nanotechnology Centre
- Griffith University
- Nathan Campus
- Australia
| | - Shayna Sharma
- Exosome Biology Laboratory
- Centre for Clinical Diagnostics
- University of Queensland Centre for Clinical Research
- Royal Brisbane and Women's Hospital
- The University of Queensland
| | - Md Abdur Rashid
- Department of Pharmaceutics
- College of Pharmacy
- King Khalid University
- Abha
- Kingdom of Saudi Arabia
| | - Yahya Alhamhoom
- Department of Pharmaceutics
- College of Pharmacy
- King Khalid University
- Abha
- Kingdom of Saudi Arabia
| | - Yoon-Bo Shim
- Department of Chemistry and Institute of BioPhysio Sensor Technology (IBST)
- Pusan National University
- Busan 46241
- Republic of Korea
| | - Carlos Salomon
- Exosome Biology Laboratory
- Centre for Clinical Diagnostics
- University of Queensland Centre for Clinical Research
- Royal Brisbane and Women's Hospital
- The University of Queensland
| | - Muhammad J. A. Shiddiky
- School of Environment and Science
- Griffith University
- Nathan Campus
- Australia
- Queensland Micro and nanotechnology Centre
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27
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Salminen L, Nadeem N, Jain S, Grènman S, Carpén O, Hietanen S, Oksa S, Lamminmäki U, Pettersson K, Gidwani K, Huhtinen K, Hynninen J. A longitudinal analysis of CA125 glycoforms in the monitoring and follow up of high grade serous ovarian cancer. Gynecol Oncol 2019; 156:689-694. [PMID: 31889528 DOI: 10.1016/j.ygyno.2019.12.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Revised: 12/17/2019] [Accepted: 12/18/2019] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Cancer antigen 125 (CA125) is generally considered the gold standard of biomarkers in the diagnosis and monitoring of high grade serous ovarian carcinoma (HGSC). We recently reported, that two CA125 glycoforms (CA125-STn and CA125-MGL) have a high specificity to HGSC and further hypothesized, that these cancer specific glycoforms are feasible candidates as biomarkers in HGSC treatment and follow up. METHODS Our cohort consisted of 122 patients diagnosed with HGSC. Serum samples were collected longitudinally at the time of diagnosis, during treatment and follow up. Serum levels of CA125, CA125-STn and CA125-MGL were determined and compared or correlated with different end points (tumor load assessed intraoperatively, residual disease, treatment response, progression free survival). RESULTS Serum CA125-STn levels at diagnosis differentiated patients with low tumor load and high tumor load (p = 0,030), indicating a favorable detection of tumor volume. Similarly, the CA125-STn levels at diagnosis were significantly lower in patients with subsequent complete cytoreduction than in patients with suboptimal cytoreduction (p = 0,025). Conventional CA125 did not differentiate these patients (p = 0,363 and p = 0,154). The CA125-STn nadir value predicted the progression free survival of patients. The detection of disease relapse was improved with CA125-STn, which presented higher fold increase in 80,0% of patients and earlier increase in 37,0% of patients. CONCLUSIONS CA125-STn showed promise as a useful biomarker in the monitoring and follow up of patients with HGSC utilizing a robust and affordable technique. Our findings are topical as a suitable indicator of tumor load facilitates patient selection in an era of new targeted therapies.
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Affiliation(s)
- Liina Salminen
- Department of Obstetrics and Gynecology, Turku University Hospital and University of Turku, Turku, Finland
| | - Nimrah Nadeem
- Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland
| | - Shruti Jain
- Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland
| | - Seija Grènman
- Department of Obstetrics and Gynecology, Turku University Hospital and University of Turku, Turku, Finland
| | - Olli Carpén
- Institute of Biomedicine, Research Center for Cancer, Infections and Immunity, Department of Pathology, University of Turku, Finland; Department of Pathology and Genome Scale Biology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Sakari Hietanen
- Department of Obstetrics and Gynecology, Turku University Hospital and University of Turku, Turku, Finland
| | - Sinikka Oksa
- Department of Obstetrics and Gynecology, Satakunta Central Hospital, Finland
| | - Urpo Lamminmäki
- Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland
| | - Kim Pettersson
- Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland
| | - Kamlesh Gidwani
- Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland
| | - Kaisa Huhtinen
- Institute of Biomedicine, Research Center for Cancer, Infections and Immunity, Department of Pathology, University of Turku, Finland
| | - Johanna Hynninen
- Department of Obstetrics and Gynecology, Turku University Hospital and University of Turku, Turku, Finland.
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28
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Uddin MJ, Wilson AJ, Crews BC, Malerba P, Uddin MI, Kingsley PJ, Ghebreselasie K, Daniel CK, Nickels ML, Tantawy MN, Jashim E, Manning HC, Khabele D, Marnett LJ. Discovery of Furanone-Based Radiopharmaceuticals for Diagnostic Targeting of COX-1 in Ovarian Cancer. ACS OMEGA 2019; 4:9251-9261. [PMID: 31172046 PMCID: PMC6545551 DOI: 10.1021/acsomega.9b01093] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 05/09/2019] [Indexed: 05/03/2023]
Abstract
In vivo targeting and visualization of cyclooxygenase-1 (COX-1) using multimodal positron emission tomography/computed tomography imaging represents a unique opportunity for early detection and/or therapeutic evaluation of ovarian cancer because overexpression of COX-1 has been characterized as a pathologic hallmark of the initiation and progression of this disease. The furanone core is a common building block of many synthetic and natural products that exhibit a wide range of biological activities. We hypothesize that furanone-based COX-1 inhibitors can be designed as imaging agents for the early detection, delineation of tumor margin, and evaluation of treatment response of ovarian cancer. We report the discovery of 3-(4-fluorophenyl)-5,5-dimethyl-4-(p-tolyl)furan-2(5H)-one (FDF), a furanone-based novel COX-1-selective inhibitor that exhibits adequate in vivo stability, plasma half-life, and pharmacokinetic properties for use as an imaging agent. We describe a novel synthetic scheme in which a Lewis acid-catalyzed nucleophilic aromatic deiodo[18F]fluorination reaction is utilized for the radiosynthesis of [18F]FDF. [18F]FDF binds efficiently to COX-1 in vivo and enables sensitive detection of ovarian cancer in subcutaneous and peritoneal xenograft models in mice. These results provide the proof of principle for COX-1-targeted imaging of ovarian cancer and identify [18F]FDF as a promising lead compound for further preclinical and clinical development.
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Affiliation(s)
- Md. Jashim Uddin
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
- E-mail: . Phone: 615-484-8674. Fax: 615.343-0704 (M.J.U.)
| | - Andrew J. Wilson
- Department of Obstetrics & Gynecology, Women’s
Reproductive
Health Research Center, and Department of Ophthalmology and Visual Sciences,
Vanderbilt Eye Institute, Vanderbilt University
Medical Center, Nashville, Tennessee 37232, United States
| | - Brenda C. Crews
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Paola Malerba
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
- Department
of Pharmacy & Pharmaceutical Sciences, University of Bari “A. Moro”, Via Orabona 4, 70125 Bari, Italy
| | - Md. Imam Uddin
- Department of Obstetrics & Gynecology, Women’s
Reproductive
Health Research Center, and Department of Ophthalmology and Visual Sciences,
Vanderbilt Eye Institute, Vanderbilt University
Medical Center, Nashville, Tennessee 37232, United States
| | - Philip J. Kingsley
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Kebreab Ghebreselasie
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Cristina K. Daniel
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Michael L. Nickels
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Mohammed N. Tantawy
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Elma Jashim
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
- Martin Luther
King Jr. Academic Magnet School of Health Sciences and Engineering, 613 17th Avenue North, Nashville, Tennessee 37203, United States
| | - H. Charles Manning
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Dineo Khabele
- Department of Obstetrics & Gynecology, Women’s
Reproductive
Health Research Center, and Department of Ophthalmology and Visual Sciences,
Vanderbilt Eye Institute, Vanderbilt University
Medical Center, Nashville, Tennessee 37232, United States
- Department
of Obstetrics and Gynecology, University
of Kansas School of Medicine, Kansas
City, Kansas 66160, United States
| | - Lawrence J. Marnett
- A. B.
Hancock, Jr., Memorial Laboratory for Cancer Research, Department
of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute
of Chemical Biology, Vanderbilt-Ingram Cancer Center,
and Department of Radiology
and Radiological Sciences, Vanderbilt Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
- E-mail: (L.J.M.)
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Abstract
OBJECTIVE The purpose of this article is to review the most commonly used tumor markers in abdominal and pelvic tumors, describe their limitations and explain how to use them in the context of known cancer in order to optimize multidisciplinary care of oncologic patients. CONCLUSION Tumor markers are important for the diagnosis, staging, monitoring of treatment and detection of recurrence in many cancers. This knowledge is crucial in the daily interpretation of images of oncologic and non-oncologic patients. However, radiologists should also be aware of the limitations of the most commonly used tumor markers and they should not be used solely, but interpreted in conjunction with diagnostic imaging, clinical history and physical examination that will help optimize the multidisciplinary care and management of oncologic patients.
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Carvalho VPD, Grassi ML, Palma CDS, Carrara HHA, Faça VM, Candido Dos Reis FJ, Poersch A. The contribution and perspectives of proteomics to uncover ovarian cancer tumor markers. Transl Res 2019; 206:71-90. [PMID: 30529050 DOI: 10.1016/j.trsl.2018.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 11/07/2018] [Accepted: 11/13/2018] [Indexed: 12/13/2022]
Abstract
Despite all the advances in understanding the mechanisms involved in ovarian cancer (OC) development, many aspects still need to be unraveled and understood. Tumor markers (TMs) are of special interest in this disease. Some aspects of clinical management of OC might be improved by the use of validated TMs, such as differentiating subtypes, defining the most appropriate treatment, monitoring the course of the disease, or predicting clinical outcome. The Food and Drug Administration (FDA) has approved a few TMs for OC: CA125 (cancer antigen 125; monitoring), HE4 (Human epididymis protein; monitoring), ROMA (Risk Of Malignancy Algorithm; HE4+CA125; prediction of malignancy) and OVA1 (Vermillion's first-generation Multivariate Index Assay [MIA]; prediction of malignancy). Proteomics can help advance the research in the field of TMs for OC. A variety of biological materials are being used in proteomic analysis, among them tumor tissues, interstitial fluids, tumor fluids, ascites, plasma, and ovarian cancer cell lines. However, the discovery and validation of new TMs for OC is still very challenging. The enormous heterogeneity of histological types of samples and the individual variability of patients (lifestyle, comorbidities, drug use, and family history) are difficult to overcome in research protocols. In this work, we sought to gather relevant information regarding TMs, OC, biological samples for proteomic analysis, as well as markers and algorithms approved by the FDA for use in clinical routine.
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Affiliation(s)
| | - Mariana Lopes Grassi
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | - Camila de Souza Palma
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | | | - Vitor Marcel Faça
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | | | - Aline Poersch
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil.
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Grayson K, Gregory E, Khan G, Guinn BA. Urine Biomarkers for the Early Detection of Ovarian Cancer - Are We There Yet? BIOMARKERS IN CANCER 2019; 11:1179299X19830977. [PMID: 30833816 PMCID: PMC6393943 DOI: 10.1177/1179299x19830977] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 01/24/2019] [Indexed: 12/20/2022]
Abstract
Ovarian cancer affects around 7500 women in the United Kingdom every year. Despite this, there is no effective screening strategy or standard treatment for ovarian cancer. If diagnosed during stage I, ovarian cancer has a 90% 5-year survival rate; however, there is usually a masking of symptoms which leads to an often late-stage diagnosis and correspondingly poor survival rate. Current diagnostic methods are invasive and consist of a pelvic examination, transvaginal ultrasonography, and blood tests to detect cancer antigen 125 (CA125). Unfortunately, surgery is often still required to make a positive diagnosis. To address the need for accurate, specific, and non-invasive diagnostic methods, there has been an increased interest in biomarkers identified through non-invasive tests as tools for the earlier diagnosis of ovarian cancer. Although most studies have focused on the identification of biomarkers in blood, the ease of availability of urine and the high patient compliance rates suggest that it could provide a promising resource for the screening of patients for ovarian cancer.
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Affiliation(s)
- Kelly Grayson
- Department of Biomedical Sciences, University of Hull, Hull, UK
| | - Ebony Gregory
- Department of Biomedical Sciences, University of Hull, Hull, UK
| | - Ghazala Khan
- Department of Biomedical Sciences, University of Hull, Hull, UK
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32
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Evaluation of serum adenosine deaminase and its isoenzymes in patients with ovarian cancer. UKRAINIAN BIOCHEMICAL JOURNAL 2018. [DOI: 10.15407/ubj90.04.111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Zhang N, Xu J, Wang Y, Heng X, Yang L, Xing X. Loss of opioid binding protein/cell adhesion molecule-like gene expression in gastric cancer. Oncol Lett 2018; 15:9973-9977. [PMID: 29805691 DOI: 10.3892/ol.2018.8562] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Accepted: 05/17/2017] [Indexed: 12/11/2022] Open
Abstract
Previous studies have reported that the expression of the opioid binding protein/cell adhesion molecule-like (OPCML) gene was frequently downregulated in various of types of cancer. However, little is known regarding the expression of the OPCML gene in gastric cancer. The present study identified that OPCML was downregulated in the gastric cancer SGC7901, KATO III, MKN45, MKN74, SNU1, AGS, N87 and a gastric mucosa cell line GES1, compared with normal gastric tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To investigate whether the downregulation of OPCML was due to promoter hypermethylation, the methylation of the OPCML promoter was assessed by methylation-specific polymerase chain reaction. Hypermethylation of the OPCML promoter was observed in the gastric cancer MKN45 cell lines, but was not as evident in normal gastric tissue. The methylation inhibitor 5-aza-2'-deoxycytidine was used to remove the methylation of the OPCML gene promoter, following which the expression of OPCML was restored. In addition, the function of the OPCML gene was studied in vitro, and it was found that the restoration expression of OPCML could lead to the suppression of cell growth. In conclusion, the present study has shown that OPCML, which acts as a tumor suppressor, was silenced in gastric cancer cell lines via aberrant hypermethylation of the promoter CpG islands, which may provide a novel molecular approach for the early diagnosis of gastric cancer.
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Affiliation(s)
- Ning Zhang
- Department of Respiratory Disease, Affiliated LuoHu Hospital of Shenzhen University, Shenzhen, Guangdong 518001, P.R. China
| | - Jide Xu
- Department of Physiology, Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
| | - Yuhong Wang
- Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510000, P.R. China
| | - Xuhua Heng
- Department of Cardiogy, Affiliated Hospital of Panzhihua University, Panzhihua, Sichuan 617000, P.R. China
| | - Liteng Yang
- Department of Respiratory Disease, Affiliated LuoHu Hospital of Shenzhen University, Shenzhen, Guangdong 518001, P.R. China
| | - Xiangbin Xing
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510000, P.R. China
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Immunohistochemical Characterization of Normal Ovary and Common Epithelial Ovarian Neoplasm with a Monoclonal Antibody to Cytokeratin and Vimentin. IRANIAN JOURNAL OF PATHOLOGY 2018; 13:23-29. [PMID: 29731792 PMCID: PMC5929385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 04/26/2017] [Indexed: 10/29/2022]
Abstract
BACKGROUND & OBJECTIVE The common epithelial ovarian tumors are classified into serous, mucinous, clear cell, endometrioid, the Brenner, mixed, and undifferentiated types. Cytoskeleton intermediate filament composition of ovarian tissues indicates that the cytokeratin and vimentin are observed in ovarian surface epithelium along with the common ovarian epithelial tumors. The current study aimed at investigating the cytokeratin and vimentin expression in epithelial ovarian tumors to establish a diagnostic relevance. METHODS Sixty-six common epithelial ovarian tumors were studied using anti-cytokeratins (Monoclonal Mouse Anti-Human Cytokeratin Clones AE1/AE3; DAKO, Denmark,) and anti-vimentin (Monoclonal Mouse Anti-Vimentin, Clone V9; DAKO, Denmark,) to ascertain the intermediate filament profiles in formalin-fixed and paraffin-embedded surgical pathology materials. RESULTS All ovarian epithelial tumors expressed cytokeratin in a uniform fashion. Vimentin was coexpressed with high intensity in 62.5% of serous carcinomas, mild intensity in 25% of mucinous adenocarcinoma, and moderate intensity in single case of endometrioid adenocarcinoma. Vimentin decoration in mucinous carcinoma had a focal involvement, whereas malignant endometrioid and serous decoration tended to involve larger areas. There was a significantly increased expression of vimentin in serous cystadenoma and serous carcinoma, compared with their mucinous counterparts. Also, vimentin expression and histologic grade of serous tumors showed a positive correlation. No association was found between vimentin expression and degree of differentiation in mucinous, endometrioid, and Brenner tumors. CONCLUSION The current investigation emphasized the efficiency of immunohistochemistry (IHC) typing as a tool for a more precise characterization of the origin and differentiation of human neoplasms.
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35
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Diagnostic and Prognostic Biomarkers in ovarian cancer and the potential roles of cancer stem cells – An updated review. Exp Cell Res 2018; 362:1-10. [DOI: 10.1016/j.yexcr.2017.10.018] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Accepted: 10/20/2017] [Indexed: 01/06/2023]
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36
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Dora SK, Dandapat AB, Pande B, Hota JP. A prospective study to evaluate the risk malignancy index and its diagnostic implication in patients with suspected ovarian mass. J Ovarian Res 2017; 10:55. [PMID: 28806987 PMCID: PMC5556625 DOI: 10.1186/s13048-017-0351-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 08/02/2017] [Indexed: 11/13/2022] Open
Abstract
Background There is no universal screening method for discrimination between benign and malignant adnexal masses yet. Various authors have tried tumor markers, imaging studies, cytology but no one yet is a definite method for screening of cancer ovary, for which a combined diagnostic modality has come to practice in form of RMI. With this background we conducted our study “Evaluation of risk malignancy index and its diagnostic value in patients with adnexal masses”. Methods The aim of the study was to determine the effectiveness of risk of malignancy index (RMI-3) in preoperative discrimination between benign and malignant masses and also to reveal the most suitable cut off value. We have conducted a prospective study between November 2014 to October 2016. We included the parameters like menopausal status, ultrasound features, and serum levels of tumor marker like CA-125 for calculating RMI 3. Then RMI was compared with the histopathological report which was taken as gold standard. Results In the present study malignant tumors constitute 54.76% (69/126) & benign tumors 45.24% (57/126). Bilaterality in adnexal masses and multilocularity is higher in malignant tumors than benign tumor, but a P –value >0.005 failed to be proved significant in our study. Solid area is seen in 24.69% (20/81) of benign and 75.30% (61/81) of malignant tumor. Similarly ascites was found in 38.09% (48/126) of cases. Out of which 18.75% (9/48) cases were found to be benign and malignancy was confirmed in 81.25% (39/48) patients. There is statistically significant number of malignant ovarian cancer patients where ascites and solid area is seen in USG findings (p = 0.000). Risk of Malignancy Index compared with individual parameters of Ultrasound score, CA-125 or menopausal score and a cut-off point of 236 shows a very high sensitivity (72.5%), specificity (98.2%), positive predictive value (98.1%), negative predictive value (74.7%) and diagnostic accuracy (84.13%) for discriminating malignant and benign pelvic masses. Conclusion Simplicity and applicability of the method in the primary evaluation of patients with pelvic masses makes it a good option in daily clinical practice in non-specialized gynecologic departments and also in developing countries where access to a gynaecologist oncologist is limited.
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Affiliation(s)
- Santosh Kumar Dora
- Department of obstetrics and gynaecology, Veer Surendra Sai Institute of Medical Science And Research (VIMSAR), Burla, Sambalpur, Odisha, India.
| | - Atal Bihari Dandapat
- Department of obstetrics and gynaecology, Veer Surendra Sai Institute of Medical Science And Research (VIMSAR), Burla, Sambalpur, Odisha, India
| | - Benudhar Pande
- Department of obstetrics and gynaecology, Veer Surendra Sai Institute of Medical Science And Research (VIMSAR), Burla, Sambalpur, Odisha, India
| | - Jatindra Prasad Hota
- Department of obstetrics and gynaecology, Veer Surendra Sai Institute of Medical Science And Research (VIMSAR), Burla, Sambalpur, Odisha, India
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Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell 2017; 32:185-203.e13. [PMID: 28810144 PMCID: PMC5964983 DOI: 10.1016/j.ccell.2017.07.007] [Citation(s) in RCA: 1349] [Impact Index Per Article: 168.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 03/27/2017] [Accepted: 07/17/2017] [Indexed: 12/11/2022]
Abstract
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.
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Sato S, Kato T, Abe K, Hanaoka T, Yano Y, Kurosaki A, Yasuda M, Sekino T, Fujiwara K, Hasegawa K. Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. Oncol Lett 2017; 14:776-786. [PMID: 28693233 PMCID: PMC5494608 DOI: 10.3892/ol.2017.6254] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 02/17/2017] [Indexed: 12/17/2022] Open
Abstract
Krebs von den Lungen-6 (KL-6), a mucinous sialylated sugar chain on human mucin-1 glycoprotein (MUC1), is a diagnostic marker for interstitial lung diseases. Furthermore, elevated serum KL-6 levels have been observed in certain malignant tumor types of epithelial origin. The expression of MUC1 has been observed in patients with epithelial ovarian cancer (EOC) and is considered a potential therapeutic target. In the present study, KL-6 serum levels were investigated in patients clinically suspected of having malignant ovarian tumors. A total of 219 patients were enrolled in the study, which analyzed their serum KL-6 levels in addition to tumor expression of MUC1 using immunohistochemistry. High serum KL-6 levels were predominantly observed in patients with EOC, and did not occur in patients with benign or borderline tumors. The level of serum KL-6 was highly correlated with tumor stage, grade and histological type, and demonstrated superior sensitivity for the detection of ovarian cancer compared with that of serum cancer antigen 125. High serum KL-6 was significantly associated with shorter progression-free survival. In addition, tumor MUC1 expression status was significantly correlated with serum KL-6 levels. These data suggest that serum KL-6 may be a useful, non-invasive biomarker surrogate for tumor MUC1 expression in future clinical trials of MUC1-targeted therapy.
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Affiliation(s)
- Sho Sato
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.,Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama 350-1298, Japan
| | - Tomomi Kato
- Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan
| | - Kenji Abe
- Department of Research and Development, Eidia Co., Ltd, Inashiki, Ibaraki 300-1155, Japan
| | - Tatsuya Hanaoka
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.,Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama 350-1298, Japan
| | - Yuri Yano
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan
| | - Akira Kurosaki
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.,Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama 350-1298, Japan
| | - Masanori Yasuda
- Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan
| | - Tetsuo Sekino
- Department of Research and Development, Eidia Co., Ltd, Inashiki, Ibaraki 300-1155, Japan
| | - Keiichi Fujiwara
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.,Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama 350-1298, Japan
| | - Kosei Hasegawa
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.,Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama 350-1298, Japan
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Pierredon S, Ribaux P, Tille JC, Petignat P, Cohen M. Comparative secretome of ovarian serous carcinoma: Gelsolin in the spotlight. Oncol Lett 2017; 13:4965-4973. [PMID: 28599499 DOI: 10.3892/ol.2017.6096] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 12/16/2016] [Indexed: 01/19/2023] Open
Abstract
Ovarian cancer is one of the most common types of reproductive cancer, and has the highest mortality rate amongst gynecological cancer subtypes. The majority of ovarian cancers are diagnosed at an advanced stage, resulting in a five-year survival rate of ~30%. Early diagnosis of ovarian cancer has improved the five-year survival rate to ≥90%, thus the current imperative requirement is to identify biomarkers that would allow the early detection, diagnosis and monitoring of the progression of the disease, or of novel targets for therapy. In the present study, secreted proteins from purified ovarian control, benign and cancer cells were investigated by mass spectrometry, in order to identify novel specific markers that are easy to quantify in patients sera. A total of nine proteins revealed significant differential secretion from control and benign cells, in comparison with ovarian cancer cells. The mRNA expression levels of three of these proteins (Dickkopf protein 3, heat shock protein 10 kDa and gelsolin) were subsequently evaluated by reverse transcription-quantitative polymerase chain reaction. Combined with the protein level in serum, the present study identified that gelsolin may be a useful marker of ovarian cancer.
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Affiliation(s)
- Sandra Pierredon
- Department of Gynecology and Obstetrics, Faculty of Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland
| | - Pascale Ribaux
- Department of Gynecology and Obstetrics, Faculty of Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland
| | | | - Patrick Petignat
- Department of Gynecology and Obstetrics, Faculty of Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland
| | - Marie Cohen
- Department of Gynecology and Obstetrics, Faculty of Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland
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Xu X, Qiu J, Sun Y. The basics of CAR T design and challenges in immunotherapy of solid tumors - Ovarian cancer as a model. Hum Vaccin Immunother 2017; 13:1548-1555. [PMID: 28272967 DOI: 10.1080/21645515.2017.1291473] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Chimeric antigen receptor T cells are T cells genetically engineered with CAR constructs which mainly contain scFV and TCR zeta chain. With promising development in blood cancers, CAR T trials are also applied in solid cancers. However, the treatment effect in solid cancers is lower than expected. This review summarizes difference of CAR T applications in solid and blood cancers. Future challenges of CAR T cell treatment in solid cancer are also discussed using ovarian cancer as an example.
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Affiliation(s)
- Xuequn Xu
- a Department of Obstetrics and Gynecology , Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University , Shanghai , China
| | - Jin Qiu
- a Department of Obstetrics and Gynecology , Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University , Shanghai , China
| | - Yi Sun
- a Department of Obstetrics and Gynecology , Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University , Shanghai , China
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Zhao T, Hu W. CA125 and HE4: Measurement Tools for Ovarian Cancer. Gynecol Obstet Invest 2016; 81:430-5. [PMID: 27160726 DOI: 10.1159/000442288] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 11/05/2015] [Indexed: 12/22/2022]
Abstract
AIMS This study aimed to examine the clinical significance of carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) serum levels in combination for ovarian cancer detection in patients. METHODS In total, 75 patients with ovarian cancer, 86 patients with benign ovarian tumors, 75 patients with endometriosis and 34 healthy women (as a control group) were selected from January 2012 to July 2015 at Anhui province hospitals. The sensitivity and specificity of detection of CA125, HE4 and combined CA125 + HE4 in serum were analyzed for each group. RESULTS HE4 and CA125 serum levels in the ovarian cancer group were higher than those in the other 3 groups (p < 0.001). The sensitivity of CA125 was higher than that of HE4 (88.2 vs. 54.7%, respectively), whereas the specificity of HE4 was higher than that of CA125 (97.9 vs. 67.4%, respectively). In contrast, the sensitivity and specificity of HE4 combined with CA125 were 82.7 and 91.4%, respectively. The receiver operating characteristic-area under the curve values of HE4, CA125 and HE4 + CA125 were 0.889, 0.893 and 0.925, respectively. CONCLUSIONS Combined detection of CA125 with HE4 can improve the sensitivity and specificity of ovarian cancer diagnosis and has certain clinical significance that can guide treatment planning.
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Affiliation(s)
- Tingting Zhao
- Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui Province, China
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Tamir A, Gangadharan A, Balwani S, Tanaka T, Patel U, Hassan A, Benke S, Agas A, D'Agostino J, Shin D, Yoon S, Goy A, Pecora A, Suh KS. The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer. J Ovarian Res 2016; 9:20. [PMID: 27036110 PMCID: PMC4815131 DOI: 10.1186/s13048-016-0228-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 03/17/2016] [Indexed: 12/19/2022] Open
Abstract
Background Ovarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC. Methods Potential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines. OVC-specific overexpression of a candidate gene, PRSS8, which encodes prostasin, was confirmed against 18 major human cancer types from 390 cancer samples by qRT-PCR. PRSS8 expression profiles stratified by OVC tumor stage-, grade- and subtype were generated using cDNA samples from 159 OVC samples. Cell-specific expression and localization of prostasin was determined by immunohistological tissue array analysis of more than 500 normal, benign, and cancerous ovarian tissues. The presence of prostasin in normal, benign, and OVC serum samples was also determined. Results Gene expression analysis indicated that PRSS8 was expressed in OVC at levels more than 100 fold greater than found in normal or benign ovarian lesions. This overexpression signature was found in early stages of OVC and was maintained in higher stages and grades of OVC. The PRSS8 overexpression signature was specific for OVC and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpressed PRSS8. In situ hybridization and histopathology studies of OVC tissues indicated that overexpression of prostasin was largely localized to tumor epithelium and was absent in neighboring stroma. Significantly higher levels of prostasin were found in early stage OVC serum samples compared to benign ovarian and normal donor samples. Conclusions The abundant amounts of secreted prostasin found in sera of early stage OVC can potentially be used as a minimally invasive screening biomarker for early stage OVC. Overexpression of PRSS8 mRNA and high levels of prostasin in multiple subtypes of early stage ovarian tumors may provide clinical biomarkers for early detection of OVC, which can potentially be used with CA125 and HE4. Electronic supplementary material The online version of this article (doi:10.1186/s13048-016-0228-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ayala Tamir
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Anju Gangadharan
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Sakshi Balwani
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Takemi Tanaka
- Stephenson Cancer Center, University of Oklahoma Health Science Center, Oklahoma city, OK, 73104, USA
| | - Ushma Patel
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Ahmed Hassan
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Stephanie Benke
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Agnieszka Agas
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Joseph D'Agostino
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Dayoung Shin
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Sunghoon Yoon
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA
| | - Andre Goy
- Clinical Divisions, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, 07601, USA
| | - Andrew Pecora
- Clinical Divisions, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, 07601, USA
| | - K Stephen Suh
- The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
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HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) as diagnostic tools for ovarian cancer in patients with a pelvic mass: An Italian multicenter study. Gynecol Oncol 2016; 141:303-311. [PMID: 26801941 DOI: 10.1016/j.ygyno.2016.01.016] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Revised: 01/14/2016] [Accepted: 01/18/2016] [Indexed: 01/03/2023]
Abstract
OBJECTIVE This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC). METHODS A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC). RESULTS Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%). CONCLUSIONS Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.
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Abstract
The purpose of this review is to give a brief background to enable the judicious use of widely performed serum cancer markers. The markers could be product of cancerous cell or as response to cancer. They are usually proteins, which are mainly found in blood or urine. These markers may be employed to predict primary or secondary tumor risk. Sometimes, non-cancerous conditions can also cause elevation of some tumor markers to be higher than normal. Besides, not every cancer patient may have raised level of a tumor marker. For these reasons, knowledge about cancer biomarkers has increased tremendously. Awareness for cancer and related tumor markers providing great opportunities for improving the management of cancer patients by enhancing the efficiency of detection and efficacy of treatment.
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Affiliation(s)
- Madhav Nagpal
- Department of Oral Medicine and Radiology, SGT, Gurgaon, Haryana, India
| | - Shreya Singh
- Department of Oral and Maxillofacial Pathology and Microbiology, Uttaranchal Dental and Medical Research Institute, Dehradun, Uttarakhand, India
| | - Pranshu Singh
- Department of Oral Maxillofacial Surgery, KGMC, Lucknow, India
| | - Pallavi Chauhan
- Department of Oral Medicine and Radiology, Sri Bankey Bihari Dental College, Ghaziabad, Uttar Pradesh, India
| | - Meesam Abbas Zaidi
- Department of Oral and Maxillofacial Pathology and Microbiology, Uttaranchal Dental and Medical Research Institute, Dehradun, Uttarakhand, India
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Is Risk Malignancy Index a Useful Tool for Predicting Malignant Ovarian Masses in Developing Countries? Obstet Gynecol Int 2015; 2015:951256. [PMID: 26185497 PMCID: PMC4491399 DOI: 10.1155/2015/951256] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 06/14/2015] [Indexed: 12/18/2022] Open
Abstract
Introduction. Risk of Malignancy Index (RMI) is widely studied for prediction of malignant pelvic masses in Western population. However, little is known regarding its implication in the developing countries. The objective of this study is to determine how accurately the RMI can predict the malignant pelvic masses. Materials and Methods. The study is a retrospective review of patients attending the gynecological clinic between January 2004 and December 2008 with adnexal masses. Information on demographic characteristics, ultrasound findings, menopausal status, CA125, and histopathology was collected. RMI score for each patient in the study group was calculated. Results. The study group included a total of 283 patients. Analysis of the individual parameters of RMI revealed that ultrasound was the best predictor of malignancy with a sensitivity, specificity, and positive likelihood ratio of 78.3%, 81.5%, and 4.2, respectively. At a standard cut-off value of 250, RMI had a positive likelihood ratio of 8.1, while it was 6.8 at a cut-off of 200, albeit with comparable sensitivity and specificity. Conclusion. RMI is a sensitive tool in predicting malignant adnexal masses. A cut-off of 200 may be suitable in developing countries for triaging and early referral to tertiary care centers.
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Granato T, Porpora MG, Longo F, Angeloni A, Manganaro L, Anastasi E. HE4 in the differential diagnosis of ovarian masses. Clin Chim Acta 2015; 446:147-55. [PMID: 25892674 DOI: 10.1016/j.cca.2015.03.047] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 02/25/2015] [Accepted: 03/09/2015] [Indexed: 12/12/2022]
Abstract
Ovarian masses, a common finding among pre- and post-menopausal women, can be benign or malignant. Ovarian cancer is the leading cause of death from gynecologic malignancy among women living in industrialized countries. According to the current guidelines, measurement of CA125 tumor marker remains the gold standard in the management of ovarian cancer. Recently, HE4 has been proposed as emerging biomarker in the differential diagnosis of adnexal masses and in the early diagnosis of ovarian cancer. Discrimination of benign and malignant ovarian tumors is very important for correct patient referral to institutions specialized in care and management of ovarian cancer. Tumor markers CA125 and HE4 are currently incorporated into the "Risk of Ovarian Malignancy Algorithm" (ROMA) with menopausal status for discerning malignant from benign pelvic masses. The availability of a good biomarker such as HE4, closely associated with the differential and early diagnosis of ovarian cancer, could reduce medical costs related to more expensive diagnostic procedures. Finally, it is important to note that HE4 identifies platinum non-responders thus enabling a switch to second line chemotherapy and improved survival.
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Affiliation(s)
- Teresa Granato
- CNR-IBPM, National Research Council, Viale Regina Elena 324, 00161 Rome, Italy
| | - Maria Grazia Porpora
- Department of Gynaecology, Obstetrics and Urology, "Sapienza" University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy
| | - Flavia Longo
- Department of Molecular Medicine, "Sapienza" University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy
| | - Antonio Angeloni
- Department of Molecular Medicine, "Sapienza" University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy
| | - Lucia Manganaro
- Department of Radiology, "Sapienza", University of Rome, Viale Regina Elena 324, 00161 Roma, Italy
| | - Emanuela Anastasi
- Department of Molecular Medicine, "Sapienza" University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
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ROMA, an algorithm for ovarian cancer. Clin Chim Acta 2015; 440:143-51. [DOI: 10.1016/j.cca.2014.11.015] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Revised: 11/03/2014] [Accepted: 11/14/2014] [Indexed: 11/23/2022]
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Tsai MF, Wang CC, Chen JJW. Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in non-small cell lung cancer. World J Clin Oncol 2014; 5:865-873. [PMID: 25493224 PMCID: PMC4259948 DOI: 10.5306/wjco.v5.i5.865] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 02/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins (HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmental or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1’s role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.
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Al-Ogaidi I, Gou H, Aguilar ZP, Guo S, Melconian AK, Al-kazaz AKA, Meng F, Wu N. Detection of the ovarian cancer biomarker CA-125 using chemiluminescence resonance energy transfer to graphene quantum dots. Chem Commun (Camb) 2014; 50:1344-6. [PMID: 24345782 DOI: 10.1039/c3cc47701k] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
A cancer biomarker immuno-sensor has been developed by utilizing the chemiluminescence resonance energy transfer to graphene quantum dots.
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Affiliation(s)
- Israa Al-Ogaidi
- Department of Biotechnology
- College of Science
- University of Baghdad
- Baghdad, Iraq
- Department of Mechanical and Aerospace Engineering
| | - Honglei Gou
- Department of Mechanical and Aerospace Engineering
- West Virginia University
- Morgantown, USA
| | | | - Shouwu Guo
- Key Laboratory for Thin Film and Microfabrication of the Ministry of Education
- Research Institute of Micro/Nano Science and Technology
- Shanghai Jiao Tong University
- Shanghai 200240, China
| | - Alice K. Melconian
- Department of Biotechnology
- College of Science
- University of Baghdad
- Baghdad, Iraq
| | | | - Fanke Meng
- Department of Mechanical and Aerospace Engineering
- West Virginia University
- Morgantown, USA
| | - Nianqiang Wu
- Department of Mechanical and Aerospace Engineering
- West Virginia University
- Morgantown, USA
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50
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Gloss BS, Samimi G. Epigenetic biomarkers in epithelial ovarian cancer. Cancer Lett 2014; 342:257-63. [DOI: 10.1016/j.canlet.2011.12.036] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Revised: 12/08/2011] [Accepted: 12/12/2011] [Indexed: 12/31/2022]
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