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To compare the value of ultrasonography (USG) score, cancer antigen 125 (CA 125), human epididymis protein 4 (HE 4) and risk of malignancy algorithm (ROMA) in differential diagnosis ovarian masses.This prospective study was conducted between May 2012 and September 2013 in a single center. Eighty-four women who had an ovarian mass on imaging and underwent surgery were included. The diagnostic performances of CA 125, HE 4, ROMA score and USG score for ovarian cancer were analyzed.There were 65 (77.3 %) women with benign ovarian tumors and 19 (22.7 %) women with malignant ovarian tumors. According to receiver operating characteristic (ROC) analysis; area under curve (AUC) was 0.874 for the USG score (p0.001), 0.794 for the CA 125 (p0.001), 0.9 for the HE 4 (p0.001), and 0.893 for the ROMA (p0.001). The USG score ≥ 3 had a sensitivity of 68.4 % and specificity of 90.7 %.The CA 125 ≥ 35 IU/l, had a sensitivity of 84.2 %, specificity of 49.2 %, the HE 4 ≥ 150 pM, had a sensitivity of 84.2 %, specificity of 98.4 % and the ROMA score had a sensitivity of 84.2 %, specificity of 75.3 % CONCLUSION: The HE 4 had higher accuracy than ROMA score, USG score and CA 125, in predicting ovarian cancer. Besides, the USG score was a simple and achievable method with acceptable performance.

Variation in ligand-binding affinity of natural plasma anti-α-galactoside antibody (anti-Gal) is a plausible reason for differing anti-cancer defense among individuals since serine- and threonine-rich peptide sequences (STPS) in the cancer-specific MUC-1 antigen are surrogate ligands for this antibody. As affinity of a natural antibody could be modulated by systemic antigens by processes including affinity maturation, we examined the contribution of the size of lipoprotein(a) [Lp(a)], an efficient autologous anti-Gal-binding macromolecule that possesses variable numbers of STPS due to genetically determined size polymorphism, towards the specific activity (activity per unit mass) of anti-Gal. Binding of purified Lp(a) to FITC-labeled anti-Gal, measured in terms of increase in fluorescence of the latter, was inhibited by LDL in proportion to Lp(a) size presumably because LDL molecules also bind noncovalently and in proportion to Lp(a) size at the O-glycosylated and STPS-rich region of Lp(a). For the same reason, circulating forms of smaller Lp(a) which carried fewer or no noncovalently attached LDL molecules were more efficient ligands for the antibody than the same number of larger ones ( P

Introduction: By quantifying the measurement uncertainty (MU), both the laboratory and the physician can have an objective estimate of the results’ quality. There is significant flexibility on how to determine the MU in laboratory medicine and different approaches have been proposed by Nordtest, Eurolab and Cofrac to obtain the data and apply them in formulas. The purpose of this study is to compare three different top-down approaches for the estimation of the MU and to suggest which of these approaches could be the most suitable choice for routine use in clinical laboratories. Materials and methods: Imprecision and bias of the methods were considered as components of the MU. The bias was obtained from certified reference calibrators (CRC), proficiency tests (PT), and inter-laboratory internal quality control scheme (IQCS) programs. The bias uncertainty, the combined and the expanded uncertainty were estimated using the Nordtest, Eurolab and Cofrac approaches. Results: Using different approaches, the expanded uncertainty estimates ranged from 18.9-40.4%, 18.2-22.8%, 9.3-20.9%, and 7.1-18.6% for cancer antigen (CA) 19-9, testosterone, alkaline phosphatase (ALP), and creatinine, respectively. Permissible values for MU and total error ranged from 16.0-46.1%, 13.1-21.6%, 10.7-26.2%, and 7.5-17.3%, respectively. Conclusion: The bias was highest using PT, followed by CRC and IQCS data, which were similar. The Cofrac approach showed the highest uncertainties, followed by Eurolab and Nordtest. However, the Eurolab approach requires additional measurements to obtain uncertainty data. In summary, the Nordtest approach using IQCS data was therefore found to be the most practical formula.

The aim of this study was to assess the prognostic and predictive value of an untargeted assessment of tumor fractions in the plasma of metastatic breast cancer patients and to compare circulating tumor DNA (ctDNA) with circulating tumor cells (CTC) and conventional tumor markers. In metastatic breast cancer patients (n = 29), tumor fractions in plasma were assessed using the untargeted mFAST-SeqS method from 127 serial blood samples. Resulting z-scores for the ctDNA were compared to tumor fractions established with the recently published ichorCNA algorithm and associated with the clinical outcome. We observed a close correlation between mFAST-SeqS z-scores and ichorCNA ctDNA quantifications. Patients with mFAST-SeqS z-scores above three (34.5%) showed significantly worse overall survival (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiologically proven progression. The baseline CTC count, carcinoembryonic antigen (CEA), and cancer antigen (CA)15-5 had no prognostic impact on the outcome of patients in the analyzed cohort. This proof of principle study demonstrates the prognostic impact of ctDNA levels detected with mFAST-SeqS as a very fast and cost-effective means to assess the ctDNA fraction without prior knowledge of the genetic landscape of the tumor. Furthermore, mFAST-SeqS-based ctDNA levels provided an early means of measuring treatment response.

Aim Receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre- and post-treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis. Methods The study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method. Results We have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre- and post-treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post-intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre-intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post-treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival. Conclusion High post-treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival.

Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

The aim of the study was to evaluate the role of human epididymal secretory protein (HE4), cancer antigen 125 (CA125), and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosing benign pelvic masses in premenopausal women.Serum was collected from 391 premenopausal women with benign pelvic mass prior to surgery and from 45 healthy individuals. Serum HE4 and CA125 levels and ROMA scores were evaluated separately.Among the 391 women with benign pelvic mass, 2.3% (9/391) had elevated HE4 levels (70 pmol/L), while 37.1% (145/391) had elevated CA125 levels (35 U/mL) (p0001). Endometriosis provided false-positive results for CA125 levels in more than half of the cases but resulted in no significant change for HE4 level. In 13 gravid women with a mass, 30.8% (4/13) and 38.5% (5/13) had elevated HE4 and CA125 levels, respectively; however, the difference was not significant (p0.05). Moreover, serum levels and patient percentages for CA125 elevation significantly increased with increase in mass diameter, whereas those for HE4 did not.CA125 elevation showed random results for benign pelvic masses, while HE4 elevation showed a higher specificity. Thus, serum HE4 testing is a better approach than CA125 testing for diagnosing benign pelvic masses in premenopausal women.

Objectives: Although low-dose computed tomography has been confirmed to have meaningful diagnostic utility, lung cancer is still the leading cause of cancer-related deaths for both genders worldwide. Thus, a novel panel with a stronger diagnostic performance for lung cancer is needed. This study aimed to investigate the efficacy of a new panel in lung cancer diagnosis. Materials and Methods: The serum levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and seven autoantibodies were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. The 316 candidates enrolled in this study were randomly assigned into two groups for the training and validation of a diagnostic panel. Results: An optimal panel with four biomarkers (CEA, CA125, Annexin A1-Ab, and Alpha enolase-Ab) was established, with an area under the receiver operator characteristic (ROC) curve (AUC) of 0.897, a sensitivity of 86.5%, a specificity of 82.3%, a positive predictive value (PPV) of 88.3%, a negative predictive value (NPV) of 79.7%, and a diagnostic accuracy of 84.8% for the training group. The panel was validated, with an AUC of 0.856 and a sensitivity of 87.5% for the validation group. Furthermore, the new panel performed significantly better in lung cancer screening than did CEA and CA125 in all of the cohorts (p< .05). Conclusion: The diagnostic performance of CEA and CA125 was significantly enhanced through their combination with two autoantibodies (Annexin A1-Ab, and Alpha enolase-Ab). Optimization of the measured autoantibodies is critical for generating a panel to detect lung cancer in patients.

BACKGROUND Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. METHODS In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. RESULTS All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without (P

Background: Distinguishing between malignant and benign ovarian masses is necessary to refer patients to centers with experience in the surgical. Objectives: The aim of this study was to analyze the diagnostic value of the tumor markers, including risk of malignancy index (RMI), human epididymis protein 4 (HE4), cancer antigen125 (CA125), and risk of ovarian malignancy algorithm (ROMA) in ovarian mass. Methods: One hundred patients with ovarian masses were assessed for the tumor markers ROMA, HE4, RMI, and CA125. The sensitivity and specificity of each parameter were calculated, using receiver-operating characteristic curves (ROCs) according to the area under the curve (AUC) for each method. Results: The median CA125, HE4, RMI, and ROMA serum levels had significant difference between malignant and benign masses in the overall assessment (P < 0.001). The AUCs were 0.83 (CA125), 0.88 (HE4), 0.85 (RMI), and 0.92 (ROMA) for benign vs. malignant masses in all the patients. The comparison of ROC curves was carried out, using a pairwise comparison method, and no differences were found among 4 methods. Conclusions: The results based on the AUC markers of CA125, HE4, RMI, and ROMA revealed that the accuracy trend of ROMA was higher than that of CA125, HE4, and RMI in all the patients and each group of pre- and post-menopausal patients.

Cancer antigen 125 (also known as carbohydrate antigen 125 or CA 125) is an antigen first identified by Bast et al. Although much research has been done to understand the molecular structure of CA 125, its function remains a source of much speculation. At present, CA 125 is most commonly used in the diagnosis of epithelial non-mucinous ovarian cancers, and in monitoring their response to treatment. Following surgical resection, CA 125 levels are expected to half within 10 days and it is therefore a useful tool for assessing response to treatment as well. We present a case of incidental finding of rasied CA125, followed by the literature review to discuss a better understanding of the factors that lead to CA 125 production, its mechanisms of action, and the nature and functions of its subspecies may help in improving its use as a standalone diagnostic tool.

Objective To identify the power of tumor markers for predicting ovarian cancer according to menopausal status. Methods The medical records of 876 women with ovarian cysts were retrospectively reviewed. Cancer antigen 125 (CA 125), human epididymis protein 4 (HE4), and Risk of Ovarian Malignancy Algorithm (ROMA) were analyzed. Sensitivity, specificity, and the receiver operating characteristic (ROC) curve analyses of these tumor markers were evaluated. Results The sensitivity of ROMA was 66.7% and the specificity was 86.8% to detect ovarian malignancy. The patients were divided into 2 groups according to menopausal status: premenopause (n=532, 60.7%) and postmenopause (n=344, 39.3%). For diagnostic accuracy, ROMA was lower than HE4 in premenopausal women (82.7% vs. 91.4%) and lower than CA 125 in postmenopausal women (86.9% vs. 88.7%). The ROC curve analysis revealed that the power of ROMA was not significantly better than that of HE4 in premenopausal women (area under the curve [AUC], 0.731 vs. 0.732, p=0.832), and it was also not significantly better than that of CA 125 in postmenopausal women (AUC, 0.871 vs. 0.888, p=0.440). Conclusion The discrimination power of tumor markers for ovarian cancer was different according to menopausal status. In predicting ovarian malignancy, ROMA was neither superior to HE4 in premenopausal women nor superior to CA 125 in postmenopausal women.

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)���positive and HPV���negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue���saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV���positive and HPV���negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer���testis antigens, 5 cancer���retina antigens and 8 oncogenes) and 29 HPV���antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV���positive and 209 HPV���negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c���myc, LAGE���1, MAGE���A1, ���A3, ���A4, NY���ESO���1, SpanX���a1 and p53. AR to MAGE���A3, MAGE���A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ���10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue���sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV���positive and HPV���negative HNSCC. �� In Copyright http://rightsstatements.org/vocab/InC/1.0/, What's new? Head and neck squamous cell carcinoma remains a deadly disease but new immunotherapeutic approaches are underexplored. Here the authors tested for antibody responses against human antigens to characterize the expression of such antigens in tumors positive or negative for human papillomavirus (HPV). Antibody responses were significantly different in prevalence and pattern based on HPV���status in a large patient cohort. The authors urge independent confirmation of their results but point out that multiplex serology of tumor antigens could be a promising strategy to identify immunotherapeutic targets based on HPV status., publishedVersion

Objectives: The global obesity epidemic has great impact on the prevalence of low-grade endometrial carcinoma. The preoperative tumor serum marker cancer antigen 125 (CA-125) might contribute to improved identification of high-risk patients within this group. The study aimed to investigate the prognostic value of CA-125 in relation to established preoperative prognosticators, with a focus on identifying patients with poor outcome in low-grade endometrial carcinoma (EC) patients. Methods: Prospective multicenter cohort study including all consecutive patients surgically treated for endometrial carcinoma in nine collaborating hospitals from September 2011 until December 2013. All preoperative histopathological diagnoses were reviewed in a blinded manner. Associations between CA-125 and clinicopathological features were determined. Univariable and multivariable analysis by Cox regression were used. Separate analyses were performed for preoperatively designated low-grade and high-grade endometrial carcinoma patients. Results: A total of 333 patients were analyzed. CA-125 was associated with poor prognostic features including advanced International Federation of Gynecology and Obstetrics (FIGO) stage. In multivariable analysis, age, preoperative tumor and CA-125 were significantly associated with disease-free survival (DFS); preoperative grade, tumor type, FIGO and CA-125 were significantly associated with disease-specific survival (DSS). Low-grade EC patients with elevated CA-125 revealed a DFS of 80.6% and DSS of 87.1%, compared to 92.1% and 97.2% in low-grade EC patients with normal CA-125. Conclusion: Preoperative elevated CA-125 was associated with poor prognostic features and independently associated with DFS and DSS. Particularly patients with low-grade EC and elevated CA-125 represent a group with poor outcome and should be considered as high-risk endometrial carcinoma.

Background/aims The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. Materials and methods The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. Results 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. Conclusion Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Tumor markers are molecules or substances produced by malignant tumors or the surrounding tissues that enter the circulation in detectable amounts. The majority of biomarkers are tumor-associated rather than tumor-specific and show elevated levels in multiple cancers. Tumor markers thus can be helpful for differential diagnosis but are not themselves diagnostic. In the field of gynecologic malignancies, biomarkers of ovarian cancer have been eagerly investigated owing to the difficulty in screening. Despite large efforts to develop novel biomarkers, cancer antigen 125 (CA125) has been the only biomarker clinically used, and no other marker has been able to outperform CA125. Noncoding RNAs, metabolites, and circulating tumor DNAs have recently emerged as cancer biomarkers and are being applied to clinical practice. Genomic biomarkers with predictive values are now used to select therapeutic drugs, especially molecular-targeted drugs. In this chapter, we describe ovarian cancer biomarkers in detail. In addition, biomarkers of uterine cancer and cervical cancer are summarized.

Endometriosis is one of the most common reproductive diseases of women, with some important biochemical changes in the serum. Curcumin was reported to have anti‐endometriosis, anti‐inflammatory and antioxidant activity. This study explores the changes of serum levels of Cancer Antigen 125 (CA125), leptin, resistin, homocysteine, and total antioxidant capacity (TAC) in a rat model of endometriosis and the effect of curcumin treatment on these factors. Fifty female Sprague‐Dawley rats (220–250 gr body weight) were randomly divided into control (received 0.3 mL of the vehicle), sham(stress of surgery + 0.3 mL of the vehicle) and three endometriosis groups as danazol treatment (7.2 mg/kg BW, IP), curcumin treatment (48 mg/kg BW, IP) and test (received 0.3 mL of the vehicle). Endometriosis was induced by surgically auto‐transplantation of uterine tissue to the abdominal wall and intestinal mesentery. The animals were treated for 4 weeks. On the last day, the blood sample was collected by heart puncture, and the above‐mentioned factors were measured in the sera. Leptin in the curcumin treatment group was markedly higher than all of the studied groups, except the danazol group, while there were no significant differences between other groups (P 0.05). The serum levels of TAC in the control group were significantly higher than all of the studied groups (P

BackgroundCarbohydrate antigen-125 (CA125) is an ovarian cancer marker, but recent work has examined its role in risk stratification in heart failure. A recent meta-analysis examined its prognostic value in heart failure generally. However, there has been no systematic evaluation of its role specifically in acute heart failure (AHF).MethodsPubMed and EMBASE databases were searched until 11 May 2018 for studies that evaluated the prognostic value of CA125 in AHF.ResultsA total of 129 and 179 entries were retrieved from PubMed and EMBASE. Sixteen studies (15 cohort studies, 1 randomised trial) including 8401 subjects with AHF (mean age 71 years old, 52% male, mean follow-up 13 months, range of patients 525.1±598.2) were included. High CA125 levels were associated with a 68% increase in all-cause mortality (8 studies, HRs: 1.68, 95% CI 1.36 to 2.07; p2: 74%) and 77% increase in heart failure-related readmissions (5 studies, HRs: 1.77, 95% CI 1.22 to 2.59; p2: 73%). CA125 levels were higher in patients with fluid overload symptoms and signs compared with those without them, with a mean difference of 54.8 U/mL (5 studies, SE: 13.2 U/mL; p2: 78%).ConclusionOur meta-analysis found that high CA125 levels are associated with AHF symptoms, heart failure-related hospital readmissions and all-cause mortality. Therefore, CA125 emerges as a useful risk stratification tool for identifying high-risk patients with more severe fluid overload, as well as for monitoring following an AHF episode.

BackgroundThe satisfactory prognostic indicator of gastric cancer (GC) patients after surgery is still lacking. Perioperative plasma extracellular vesicular programmed cell death ligand-1 (ePD-L1) has been demonstrated as a potential prognosis biomarker in many types of cancers. The prognostic value of postoperative plasma ePD-L1 has not been characterized.MethodsWe evaluated the prognostic value of preoperative, postoperative and change in plasma ePD-L1, as well as plasma soluble PD-L1, in short-term survival of GC patients after surgery. The Kaplan-Meier survival model and Cox proportional hazards models for both univariate and multivariate analyzes were used. And the comparison between postoperative ePD-L1 and conventional serum biomarkers (carcinoembryonic antigen (CEA), cancer antigen 19–9 (CA19-9) and CA72-4) in prognostic of GC patients was made.ResultsThe prognostic value of postoperative ePD-L1 is superior to that of preoperative ePD-L1 on GC patients after resection, and also superior to that of conventional serum biomarkers (CEA, CA19-9 and CA72-4). The levels of postoperative ePD-L1 and ePD-L1 change are independent prognostic factors for overall survival and recurrence free survival of GC patients. High plasma level of postoperative ePD-L1 correlates significantly with poor survival, while high change in ePD-L1 level brings the significant survival benefit.ConclusionsThe level of plasma postoperative ePD-L1 could be considered as a candidate prognostic biomarker of GC patients after resection.

A 65-year-old woman with a previous history of bilateral salpingo-oophorectomy had peritoneal cysts, increasing in size over 15 years and an increasing cancer antigen 19–9 (CA 19–9) level. The size of the cysts eventually reached 86 mm and 70 mm. As malignant transformation of endometriosis was suspected, we performed peritoneal cystectomy and hysterectomy. Histopathology revealed seromucinous borderline tumours (SMBTs) derived from endometriosis. One month after surgery, her CA 19-9 level had decreased. It is rare for SMBT to occur after bilateral salpingo-oophorectomy; surgical management is the best treatment at present.

BACKGROUND AND OBJECTIVES The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM. METHODS Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan. RESULTS There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023). CONCLUSIONS The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc.

Epithelial ovarian cancer (EOC) remains the deadliest form of gynecological cancers. Optimal tumor debulking, no matter the primary or the interval, is the most important prognostic factor for EOC, so there is an urgent demand for biomarkers to predict surgical outcome. The aim of this study was to investigate whether serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) could predict surgical outcome of EOC. The levels of preoperative serum HE4 and CA125 were determined by electrochemiluminescence (ECLIA) in 82 EOC patients, comprising 39 subjected to primary debulking surgery (PDS) and 43 with extensive stage III or IV disease to neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Among 39 patients subjected to primary debulking surgery, HE4 was superior to CA125 in predicting surgical outcome (area under curve [AUC] 0.758 vs. 0.633). At a cutoff of 353.22 pmol/L, HE4 reached 77.4 % in sensitivity and 75 % in specificity. The prediction of surgical outcome of interval debulking surgery based on preoperative HE4 and CA125 values was performed in 43 patients who received NACT-IDS. The difference of AUC between HE4 and CA125 (0.793 vs. 0.663) indicating that HE4 was the better biomarker to predict surgical outcome of IDS. A pre-IDS HE4 value of 154.3 pmol/L is the optimal cutoff to identify patients who would not benefit from IDS with a sensitivity of 92.9 % and a specificity of 69 %. The change (>70 %) of HE4 before and after neoadjuvant chemotherapy could predict optimal interval debulking surgery. Serum HE4 was superior to CA125 in predicting surgical outcome of primary debulking surgery and interval debulking surgery. The change (absolute value or percentage) of HE4 in neoadjuvant chemotherapy could predict the outcome of interval debulking surgery.

We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p

Objectives This study aimed to evaluate the diagnostic and prognostic value of pleural effusion levels of soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) in lung cancer patients with malignant pleural effusion (MPE). Methods Pleural effusion samples were collected from 78 patients with MPE, and from 48 patients with benign pleural effusion (BPE). Pleural effusion sRCAS1 concentrations were measured by enzyme-linked immunosorbent assay. Results MPE has significantly higher sRCAS1 levels than that of BPE (P

Tumor markers are often heterogeneous substances that may be present in elevated concentrations in the serum of cancer patients. Typically measured by immunoassay, they contribute to clinical management, particularly in screening, case-finding, prognostic assessment, and post-treatment monitoring. Data both from external quality assessment (EQA) schemes and clinical studies demonstrate significant variation in tumor marker results obtained for the same specimen using different methods. Between-method between-laboratory coefficients of variation (CV) reported by EQA schemes generally reflect the complexity of the measurand, ranging from5% for the structurally relatively simple α-fetoprotein (AFP) to25% for the complex mucinous cancer antigen 19-9 (CA19-9). Improving the standardization of tumor marker measurements is particularly important for three reasons. The primary use of tumor markers is in monitoring cancer patients over long periods of time. Clinical interpretation of trends may consequently be affected if results are obtained in different laboratories using different methods or if a laboratory has to change method. Differences in results may have major implications for adoption of area-wide decision cut-offs and make implementation of these difficult. Method-related differences also make it difficult to compare clinical studies. Improving comparability of tumor marker results requires broad international agreement about which molecular forms of the measurand have clinical utility, identifying and adopting pure molecular forms as calibrants, and defining antibody specificities for their optimal detection. These aims have been achieved to varying extents for the most frequently measured serum tumor markers as described in this paper.

The aim of the review is to summarize the modern views on etiopathogenesis and treatment of ovarian cancer, as well as to search for ways for a more personalized approach to the management of patients with this oncological disease. Despite the limited number of patients participating in clinical trials of ovarian cancer, there are obvious results of gradual evolution in its diagnosis and treatment. Studies of etiopathogenesis led to a better understanding of the ovarian cancer genesis mechanisms, whereas evolution in treatment was marked by combination of secondary cytoreductive surgery with the most effective chemotherapeutic drugs and biological agents. The introduction of biomarkers, particularly CA125 (cancer antigen 125), in the diagnostic algorithm for both primary and recurrent ovarian cancer has opened up new horizons for the application of effective methods of treatment at the disease earliest stages. However, in the landmark study of G.J. Rustin et al. there was no a statistically significant difference in disease-free and overall survival among female patients with immediate treatment of recurrent ovarian cancer based only on elevated CA125 and female patients in whom chemotherapy was initiated after the clinical symptoms manifestation. Conducting clinical trials in small cohorts of patients with certain ovarian cancer histotype will help to select one or another effective combination of chemotherapy and/or biological agents administered not only intravenously, but also intraperitoneally, and thereby provide the personalized approach to the treatment of this disease.

Current analytical methods, either point-of-care or centralized detection, are not able to meet recent demands of patient-friendly testing and increased reliability of results. Here, we describe a two-point separation on-demand diagnostic strategy based on a paper-based mass spectrometry immunoassay platform that adopts stable and cleavable ionic probes as mass reporter; these probes make possible sensitive, interruptible, storable, and restorable on-demand detection. In addition, a new touch paper spray method was developed for on-chip, sensitive, and cost-effective analyte detection. This concept is successfully demonstrated via (i) the detection of Plasmodium falciparum histidine-rich protein 2 antigen and (ii) multiplexed and simultaneous detection of cancer antigen 125 and carcinoembryonic antigen.

Objective To evaluate the value of individual and combined measurement of human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125) in the diagnosis of ovarian cancer. Methods A clinical case-control study was performed in which the levels of serum HE4 and CA-125 of subjects with malignant, borderline, benign ovarian tumors and healthy women were measured before surgery. An immunohistochemistry method was used to measure the expression of HE4 in different tissues. Statistical analysis was performed to determine the relationship between the level of HE4 and the pathologic type as well as the stage of the ovarian tumors. Results The level of HE4 in the serum was significantly elevated in the malignant ovarian cancer group compared with other groups. Women with benign ovarian tumors and non-neoplastic lesions, and healthy women were designated as references. When the level of HE4 in the serum was 58.66 pmol/L, the sensitivity and specificity of HE4 in diagnosing malignant ovarian tumors was 82.35% and 96.03%, respectively. The level of HE4 was negatively correlated with the differentiation extent of the tumors whereas positively correlated to the clinical staging. In the groups of malignant and borderline tumors, the levels of HE4 were higher than the other groups. The expression of HE4 was significant higher in the serous types of ovarian tumors than that of the mucous types (P Conclusion HE4 can be used as a novel clinical biomarker for predicting malignant ovarian tumors and its expression was closely related with the clinical pathological features of malignant ovarian tumors.

A two-step dual-label TRFIA was developed for the simultaneous detection of human epididymis protein-4 and cancer antigen 125 in a single run. The performance of this assay was first evaluated using clinical serum samples, and then compared with commercialized kits. The sensitivity of this assay for cancer antigen 125 detection was 0.5 U/mL (dynamic range, 0-1400 U/L), and the sensitivity for human epididymis protein-4 detection was 1 pM (dynamic range, 1-900 pM). High correlation coefficients (R) were obtained between the present dual-label TRFIA and commercially available kits (R = 0.99). The present dual-label TRFIA has high sensitivity, specificity, and accuracy in clinical sample analysis. It is a good alternative to the single-label diagnostic methods.

Aim: We primarily aimed to compare the levels of serum and cervicovaginal cancer antigen 125 (CA 125) in women with and without endometrial carcinoma in order to reveal whether cervicovaginal CA 125 could be used as a non-invasive method. Methods: A preliminary case-control study was designed. The study group consisted of patients who were operated for endometrial adenocarcinoma or endometrial intraepithelial neoplasia. The control group consisted of patients who underwent surgery for benign gynecological diseases. Serum and cervicovaginal secretions were immediately collected before surgery to compare levels of CA 125. Results: The mean cervicovaginal CA 125 levels in patients with endometrial cancer and controls were 1,598.1 ± 1,691.1 versus 947.0 ± 1,282.7 U/ml, respectively (p = 0.016). Whereas area under receiver operating characteristic curve was 0.62 for serum CA 125, it was 0.68 for cervicovaginal CA 125. The optimal threshold of CA 125 in cervicovaginal secretion was calculated to be 575 U/ml, which detected endometrial precancer or cancer with sensitivity of 78% and specificity of 57%. The positive and negative predictive values for this threshold were 38.7 and 88.2%, respectively. Conclusion: In conclusion, detection of CA 125 in cervicovaginal secretion has a potential role for the non-invasive screening of endometrial precancers and cancers.

In this study, a combined detection assay for determination of cancer antigen 15-3 (CA15-3) and copper level in breast cancer serum was developed by use of gold nanorod (GNR)-based plasmonic sensor. Rapid detection of tumor marker (CA15-3) can be accomplished through a simple transduction of optical signal induced by immune-reaction between CA15-3 and GNR@CA15-3 antibody. On the other hand, the copper-induced change of localized surface plasmon resonance of GNRs results in a direct readout of optical signal. Therefore, practical application for combined determination of CA15-3 and copper levels of human serum samples of breast cancer was performed. The results are close agreement with those given by the hospital or other standard approach, confirming this assay with high accuracy. The combined detection strategy provides potential applications for early diagnosing and monitoring the progress of malignant tumor.

Ovarian hemangiomas are usually of the cavernous type, and are rarely encountered. A 73-year-old woman presented with lower abdominal discomfort. Subsequent physical examination depicted a palpable mass in the lower abdomen. Abdominopelvic computed tomography (CT) revealed a well-circumscribed mass with thin septa measuring 12.1 × 9.0 cm in the right ovary. Levels of the tumor markers cancer antigen (CA)-125 and CA 19-9 were within the normal range. At laparoscopy, the tumor was found to be confined to the right ovary and to have a smooth surface. The final histopathological result was ovarian cavernous hemangioma. Microscopically, the mass consisted of multiple, dilated, blood-filled vascular channels separated by loose connective tissue, and all were lined by a single layer of flattened endothelium. The authors present a case of ovarian cavernous hemangioma presenting as a large growing mass in a postmenopausal woman and review previously published literature.

Aim We investigated whether plasma levels of lysophosphatidic acid (LPA) could serve as a diagnostic indicator for assessing disease progression in ovarian cancer (OC) patients. Material and Methods In this study, we enrolled 98 patients with OC, 70 patients with benign ovarian tumors and 75 healthy controls. Plasma levels of LPA and cancer antigen 125 (CA-125) were measured in all study subjects. The diagnostic values of LPA and CA-125 plasma levels were evaluated and an updated meta-analysis was performed to examine the association between LPA plasma levels and OC progression. Statistical analyses were performed with spss 18.0 and R 3.1.0 software. Results In our case–control study, OC patients showed significantly higher plasma LPA levels compared to patients with benign tumors and healthy controls (all P

Background: Adnexal masses present a diagnostic and therapeutic dilemma across age-groups. This study aimed to evaluate the performance of cancer antigen-125 (CA-125) in distinguishing between benign and malignant adnexal masses.Methods: This was a prospective, observational, single tertiary-care center study, done in North India from January, 2011 till December, 2012. Serum CA-125 levels was obtained preoperatively in consecutive patients presenting with ultrasonography confirmed adnexal masses. The cut-off value between benign and malignant was taken as 35 IU/ml. Histopathological diagnosis was obtained in all patients.Results: A total of 126 patients presented with adnexal masses, of which 100 were enrolled (mean age: 37.5±14.4 years, range: 18-80 years). Most of the masses were benign 81% (malignant=19%). Dermoid cyst (25.9%) and endometriomas (21%) were the most common benign masses. Serous (21%) and mucinous cystadeno-carcinoma (15.8%) were the most common malignant masses, more often seen in elderly, married, parous and post-menopausal patients. Mean CA-125 levels were significantly higher in malignant masses (257.30 [105.68-408.92] versus 19.26 [16.53-22.00], p

Background: The tumor abnormal protein (TAP) test is used to screen for many cancers, but its use for breast cancer has not been studied. Methods: Tests for carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and TAP were administered to 261 women with operable benign breast disease and 348 with breast cancer. The cutoff value used for TAP was the mean + 3 standard deviations for benign breast disease patients (275.64 μm2). Sensitivities and specificities of single biomarker tests and combined tests were compared. The combined tests were defined as positive if any single biomarker was positive, and negative otherwise. Results: The single biomarker test sensitivities were similar: CEA, 7.18%; CA125, 4.89%; CA15-3, 7.47%; and TAP, 4.89%. For the combinations TAP + CEA + CA125, TAP + CEA + CA15-3, TAP + CA125 + CA15-3, and TAP + CEA + CA125 + CA15-3, the sensitivities were 16.67%, 17.82%, 16.38%, and 21.84%, respectively, and the specificities were 93.49%, 97.70%, 93.87%, and 92.72%. Conclusions: The 4-test combination showed the highest sensitivity (21.84%) and may be auxiliary used in early screening. TAP + CEA + CA15-3 showed high specificity (97.70%) and so could be used for confirming breast cancer.

With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

Women diagnosed with late-stage ovarian cancer suffer a very high rate of mortality. Accordingly, it is imperative to detect and diagnose the disease as early as possible in its development. Achievement of this aim implies relatively large scale screening of women at an age of clinically significance through assay of biomarkers for disease present in blood or serum. Biosensor detection offers an attractive technology for the automated detection of such species. Among several biomarkers that have been identified that are present in patients with ovarian cancer, the only one that is commonly tested for in clinical use is cancer antigen 125, which is considered to be poor biomarker for the disease. Here, we describe alternative biomarkers which overcome many of the problems associated with cancer antigen 125 such as increased sensitivity and specificity especially in the early stages of the disease and which could be employed successfully in a biosensor format. In particular, we discuss the chemistry of probes for the biomarkers, heat shock protein 10 and lysophosphatidic acid. The challenges presented by the fabrication of biosensor devices for the detection of the cancer, and the limited number of biosensors that have been developed for this purpose are discussed.

© 2018 John Wiley & Sons Ltd To understand Cancer Antigen 125 (CA125) testing in primary care in relation to a national guideline, we conducted a retrospective observational study including CA125 data from a well-defined region in the UK, from 2003 to 2014. 51,033 CA125 tests from 30,737 women were stratified by month and year of testing, location of test request and patient age. Absolute numbers and rates of testing, rates and proportions of positive and negative tests, and frequencies of single and repeat tests were calculated. Negative binomial and logistic regression were used to test the effect of the guideline's introduction. Primary care testing spiked in the three months following the release of the guideline. However, there was no difference in the increase in testing observed across age groups. The proportion of positive tests decreased over time despite both the rates of positive and negative tests increasing. Retesting and repeat testing were associated with the initial CA125 value with no significant difference between women whose first test was 30–35 and >35 IU/L. Large studies using linked data are required to investigate the impact of increasing CA125 testing on onward intervention and patient outcomes. CA125 guidelines should be refined to avoid over-investigation in low risk age-groups.

Aim To investigate the prognostic value of serum cancer antigen 125 (CA125) levels during chemotherapy in relapsed epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients who relapse beyond 12 months from those who relapse within 12 months. Methods About 93 relapsed EOC patients who received cytoreductive surgery and adjuvant chemotherapy at Obstetrics and Gynecology Hospital of Fudan University between January 2003 and March 2015 were selected. Univariate regression analysis was used to determine the significant prognostic factors. The Kaplan-Meier method was used to calculate the overall survival (OS) rate. Results The CA125 decrease ratio of more than 97.6% after the fourth chemotherapy cycle was significantly associated with relapse time (P = 0.044). The sensitivity was 70.0%, and the specificity was 76.9%. Moreover, in all relapsed patients, the group with the CA125 decrease ratio after the fourth chemotherapy cycle of more than 97.6% had a significantly better OS than any other group (P = 0.0019). Conclusion The CA125 decrease ratio of less than 97.6% after the fourth chemotherapy cycle can be a predictive factor for relapse within 12 months. Patients without a significant decrease in CA125 after four cycles of chemotherapy should have a more frequent follow-up and more active re-examination.

The aim of this study is to assess the diagnostic value of lysophosphatidic acid (LPA) in epithelial ovarian cancer (EOC) patients in comparison with CA125. The study included 41 women with EOC and 41 women with benign ovarian tumor. Serum CA-125 and LPA levels were measured and correlated with histopathological examination results. Ovarian cancer patients have increased LPA and cancer antigen CA-125 levels compared to patients with benign ovarian tumor (LPA: ovarian cancer vs. benign ovarian tumor: 2.43 ± 1.69 vs. 0.6 ± 0.71 μmol/L; CA-125: ovarian cancer vs. benign ovarian tumor: 604.55 ± 865.84 vs. 86.71 ± 194.87 U/mL), which showed statistically significant differences (both P

A novel screening method for protein aptamer selection was developed in this study. Aptamers with high affinity and specificity to the surface recombinant antigen of Helicobacter pylori (HP-Ag) and to tumor markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 19-9(CA19-9) were screened using trypsin enhanced screening method. Briefly, the target proteins above were immobilized onto 96-well polystyrene plates and incubated with a single-stranded DNA (ssDNA) library for aptamer selection. Then, trypsin was introduced to digest the proteins and obtain ssDNA that bound to the target proteins with high specificity. The concentration of ssDNA that shed from protein-ssDNA complexes was detected. After sequencing, the enrichment of target-specific aptamers was monitored and the affinity of each aptamer was analyzed. Urea, which has been reported in other article, was used to compare with trypsin. The results revealed that trypsin was more effective than urea for protein aptamer selection. The protocol used in this study provided a novel method for generating aptamers.

Background Preoperative differentiation between benign and malignant masses can be challenging. The aim of this research was to evaluate the performance of a modified multivariate index assay (MIA) in detecting ovarian cancer and to compare the effectiveness of gynecologist assessment, cancer antigen (CA) 125, and MIA for identifying ovarian masses with high suspicion of malignancy. Results This prospective observational study included 150 women with ovarian masses who underwent surgery in the Maternity Teaching Hospital from December 2014 to May 2016. Preoperative estimation of modified MIA, assessment by a gynecologist, and CA 125 level correlated with the surgical histopathology. A modified MIA was implemented because of lack of access to the software typically used. Among 150 enrolled women there were 30 cases of malignancy, including 8 cases (26%) of early-stage ovarian cancer and 22 cases (74%) of late-stage cancer. MIA showed high specificity (96.7%) in detecting cancer and a sensitivity of 70%, with a positive predictive value of 84% and a negative predictive value of 92.8%. No significant differences were detected between the MIA results and the histopathology results (P = 0.267). For early-stage ovarian cancer, the sensitivity of MIA was 100% compared with 75% for CA 125 alone. Conclusion MIA seems to be effective for evaluation of ovarian tumors with higher specificity and positive predictive value than CA 125 while maintaining high negative predictive value and with only a slightly lower overall sensitivity. For evaluation of early-stage ovarian cancer, MIA showed a much higher sensitivity that markedly outperformed CA 125 alone. This modified MIA strategy may be particularly useful in low resource setting.

Background Cancer antigen (CA) 125 (CA-125) is used in ovarian cancer detection and monitoring, whose serum level has a positive correlation with tumor stage. The aim of this study was to obtain a prediction metastasis equation in a group of patients with ovarian cancer based on Ca-125. Methods A 2-group comparative observational study was conducted at a single oncologic institution (SOLCA) in Cuenca-Ecuador. All patients who were diagnosed with ovarian cancer between January 1996 and December 2016 were included in the current study. Group 1 (G1) patients with the I and II International Federation of Gynecology and Obstetrics (FIGO) stage and Metastasis Group (MG), with III and IV stage, were subdivided. A logistic regression equation was performed to predict metastasis based on Logarithm of serum Ca-125 levels. Results We included 85 cases in G1 and 64 patients in MG, with 47.8 ± 15 years (G1) and 57.5 ± 13.6 years (MG) of age (P

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.

Although considerable progress has been made in the field of cancer chemotherapy, there remains a significant unmet medical need, with a requirement to move away from traditional cytotoxics and explore novel, smarter chemotherapeutic approaches. One such example of the smart chemotherapy approach is antibody-drug conjugates (ADCs), which consist of an antibody that binds selectively to a cancer antigen linked to a cytotoxic agent. When developing an ADC, it may be necessary to produce a variety of constructs to fully assess the optimal configuration for the molecule. By testing ADCs prepared using a range of cytotoxic agents, linkers, or different antibodies, it is possible to fully assess the optimal approach for this treatment modality before advancing to the clinic. Since the development and approval of first-generation ADCs, significant improvements in development technology have occurred. Here, we consider the advances made within the field of ADCs, focusing on the development of EDO-B278 and EDO-B776, both of which have demonstrated efficacy in preclinical testing. Although some limitations remain in this field of development, the potential reduction in toxicity offered by ADCs justifies the investment in research to find workable solutions that could ultimately provide patients with superior outcomes.