Combination Of Tumor Markers Research Articles

A report of twenty cases of ovarian Brenner tumor and literature review: a case series study

BackgroundTo explore the clinical characteristics of ovarian Brenner tumors and provide some basis for the treatment regimen of ovarian Brenner tumors.MethodsA retrospective analysis of the pathology database of surgical specimens at the Huzhou Maternal and Child Health Hospital from September 2008 to February 2023 was conducted. Patients who were pathologically diagnosed with ovarian Brenner tumors were included. Clinical data of patients was collected, and their diagnostic and treatment characteristics were summarized and analyzed.ResultsA total of 20 cases were included in this study, all of which were histologically confirmed by surgical pathology. Among them, 8 cases (40%) were combined with serous, mucinous cystadenoma, or simple cyst. One case presented with a benign ovarian Brenner tumor combined with mucinous cystadenoma, underwent right adnexectomy, and relapsed 5 years later as a malignant Brenner tumor (MBT) coexisting with ovarian squamous cell carcinoma. Multiple tumor markers were elevated malignantly, with CA199 being the most significant. Treatments included unilateral adnexectomy in 7 cases, bilateral adnexectomy in 3 cases, total hysterectomy with bilateral adnexectomy in 7 cases, radical hysterectomy in 1 case, and 2 cases underwent ovarian staging surgery. MBT patients received three cycles of postoperative chemotherapy with the carboplatin-paclitaxel (TC) regimen. Follow-up: One case with concomitant cervical cancer was lost to follow-up after surgery in an external hospital; one case with concomitant ovarian cancer received no further treatment after surgery and was lost to follow-up after 2 years; one case with concomitant endometrial cancer received no further treatment after surgery, and had no recurrence after 4 years of follow-up. Regular follow-up for MBT patients continued for 5 years without recurrence. The remaining 16 cases were followed up for a period ranging from 6 months to 7 years, with no reported recurrences.ConclusionClinical manifestations and auxiliary examinations of ovarian Brenner tumors lack obvious specificity. When necessary, a combination of tumor markers and imaging examinations can aid in diagnosis. Surgical strategies should be selected according to the patient's menopausal status.Trial registrationNot applicable.

Correlation of FDG PET/CT, tumor markers and Ki-67 index with EGFR mutation or positive ALK expression in patients with non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the two most common druggable targets in non-small cell lung cancer (NSCLC). To investigate whether the EGFR mutation and ALK rearrangement could be predicted by the combination of FDG avidity, tumor markers and Ki-67 Index. A total of 168 newly diagnosed NSCLC patients who had undergone 18F-FDG PET/CT for staging were enrolled. PET/CT parameters of primary tumors including maximum standardized uptake value (pSUVmax), metabolic tumor volume (pMTV) and total lesion glycolysis (pTLG) were measured. Five serous tumor markers for lung cancer were recorded. Ki-67 labeling index was counted by immunohistochemical staining. EGFR mutation and ALK status were detected by ARMS-PCR and RT-PCR, respectively. Univariate and multivariate analyses were applied to identify the predictors of EGFR mutation and ALK positivity. EGFR mutation rate was 38.1% (64/168), which were found more frequently in female, ≤60 years old, non-smokers and adenocarcinoma patients, and were not related to lymph node involvements, distant metastases, stage and serum tumor markers. Low pSUVmax, pMTV, pTLG and Ki-67 were significantly associated with EGFR mutation. Logistic regression demonstrated that pSUVmax <6.75 and gender (female) were the independent factors affecting EGFR mutation, and the combination of them had a certain predictive value with the area under the curve of 0.784. ALK positive rate was 6.0% (10/168), all of them were adenocarcinoma patients, which were more common in non-smokers, low serum cytokeratin-19 fragment antigen (CYFRA21-1) and low Ki-67, and were not related to FDG activity. No independent factor for ALK positivity was found on Logistic regression. Low pSUVmax, rather than tumor markers or Ki-67, was correlated with EGFR mutation independently, which could be integrated with gender (female) to improve the identification for EGFR mutation in NSCLC patients.

Serum IL-24 combined with CA125 as screening and prognostic biomarkers for NSCLC.

Noninvasive and effective methods for early screening of non-small cell lung cancer(NSCLC) still need to be developed. At present, a reasonable conclusion is that a combination of tumor markers is a superior predictor of screening. Cytokines, as important regulators of cancer development, have great potential for the screening and prognosis of NSCLC. This study screened novel biomarkers related to the early screening and prognosis of NSCLC. In the present study, the biological significance and immunoregulation of interleukin-24(IL-24) were analyzed based on The Cancer Genome Atlas data. Next, 150 serum samples from initially treated patients with NSCLC and 70 controls were collected, and we obtained pathological sections from 60 patients with NSCLC. The ELISA and immunohistochemistryresults showed the differential expression of IL-24 and carbohydrate antigen 125(CA125). The results show that IL-24 is an important tumor suppressor in NSCLCthat helps to improve the poor prognosis of these patients. A significantly negative correlation between IL-24 and CA125 levels was also found. Notably, serum IL-24 levels were significantly negatively correlated with the TNM stage of patients with NSCLC, consistent with an important role for tumor suppressors in NSCLC. The receiver operating characteristic curve analysis showed that a combination of IL-24 and CA125 was an effective panel for discriminating patients with NSCLC from HD, and individuals with other lung diseases. Serum IL-24 and CA125 levels were identified as independent prognostic markers for NSCLC. The IL-24 and CA125 panel exhibited good performance in the screening of NSCLC.

Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P <0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P <0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P <0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study

BackgroundTo investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors.MethodsA multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP.ResultsThe mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone.ConclusionsThe serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance.Trial registrationClinical Trials, NCT03645655. Registered 20 August 2018, https://www.clinicaltrials.gov/ct2/show/NCT03645655.

Diagnostic Accuracy of Cancer in Pleural Effusion: A Combination Serum Tumor Markers and Cytology

Abstract Background: Cytological examination of body effusion has an essential role in different tumor staging and research of malignancy. Objectives: It is to study the diagnostic effect of serum tumor markers in differentiation between benign and malignant pleural effusion. Materials and Methods: A retrospective research was done on 39 patients (28 male and 11 female with an age range of 50–77 years old). All samples undergo diagnostic thoracocentesis. The cutoff values of serum tumor markers (CEA &lt; 5 ng/mL; CA125 &lt;35 U/mL; CA19-9 &lt; 37 U/mL; and CA15-3 &lt; 31 U/mL). Results: Thirty-nine cases, resulting in 26 (67%) benign pleural effusions and 13 (33%) malignant pleural effusions, mean ± SD of age was higher malignant pleural effusion than benign type. The sensitivity of cytology was 33%. Malignant pleural effusion tended to have higher serum marker tumor concentrations. A comparison association between benign and malignant pleural effusion revealed statistically significant only in CEA. Most areas under the curve had moderate values that ranged between 0.6 for CA125, CA15.3, and other combined tumor markers, except for CEA, which had a good AUC (0.799). The best efficacy of a single tumor marker is CEA with a cutoff value of 2.05 ng/mL; at this cutoff value, the sensitivity, specificity, and accuracy were 69.2%, 88.5%, and 82.1%, respectively. Conclusion: Single serum tumor markers showed moderate sensitivity and low specificity; their combination does not result in to increase level of sensitivity and specificity to a good and dependent level for diagnosis of the malignant pleural effusion. Cytology and serum tumor markers have aided role in diagnosis. Thoracoscopy and pleural biopsy remain dependent diagnostic tools for malignant pleural effusion.

Determination of Tumor Marker Screening for Lung Cancer Using ROC Curves.

Lung cancer ranks first among malignant tumors worldwide and is a leading cause of cancer-related mortality in both men and women. Combining tumor marker testing is a strategy to screen individuals at high risk of pulmonary cancer and minimize pulmonary cancer mortality. Therefore, tumor marker screening is crucial. In this study, we analyzed combinations of tumor markers for lung cancer screening using receiver operating characteristic (ROC) curve analysis. A retrospective descriptive study was conducted on patients diagnosed with lung cancer, as well as healthy and benign lung diseases, using data from the China Huludao Central Hospital database between January 2016 and July 2022. The t-test and ROC curve were utilized to assess the effectiveness of individual tumor marker and the combination of multiple tumor markers. Tumor markers are molecular products metabolized and secreted by tumor tissues, characterized by cells or body fluids. They serve as indicators of tumor stage and grading, monitor treatment response, and predict recurrence. In this study, 267 healthy participants, 385 patients with benign lesions, and 296 patients with lung cancer underwent tumor marker screening. The sensitivity of five tumor markers-CEA, CYFRA21-1, NSE, pro-GRP, and CA125-was found to be <55%. This study revealed that a single tumor marker had limited value in lung cancer screening. However, combining two or more markers yielded varying area under the curves (AUC), with no significant impact on screening accuracy. The combination of CEA + CA125 demonstrated the highest accuracy for lung cancer screening in healthy participants. At a cutoff of 0.447 for CEA + CA125, the combination showed a sensitivity of 0.676 and specificity of 0.846 for lung cancer screening. Conversely, for patients with benign lung lesions, the optimal combination was CEA + NSE, with a cutoff of 0.393, yielding a sensitivity of 0.645 and specificity of 0.766 for lung cancer screening. The five tumor markers-CEA, CA125, CY211, NSE, GRP-show promising results in screening healthy individuals and patients with lung cancer. However, only CEA, NSE, and GRP effectively differentiate patients with benign lung lesions from those with lung cancer. A single tumor marker has limited utility in detecting and screening for lung cancer and should be combined with other tumor markers. CEA + CA125 emerges as a superior tumor marker for distinguishing healthy individuals from those with lung cancer, whereas the CEA + NSE combination is more effective in identifying tumor markers in patients with benign lung lesions and lung cancer.

Improvement of differential diagnosis of lung cancer by use of multiple protein tumor marker combinations.

Differential diagnosis of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in hospitalized patients is crucial for appropriate treatment choice. To investigate the relevance of serum tumor markers (STMs) and their combinations for the differentiation of NSCLC and SCLC subtypes. Between 2000 and 2003, 10 established STMs were assessed retrospectively in 311 patients with NSCLC, 128 with SCLC prior systemic first-line therapy and 51 controls with benign lung diseases (BLD), by automatized electrochemiluminescence immunoassay technology. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic efficacy of both individual and multiple STMs with corresponding sensitivities at 90% specificity. Standards for Reporting of Diagnostic Accuracy (STARD guidelines) were followed. CYFRA 21-1 (cytokeratin-19 fragment), CEA (carcinoembryonic antigen) and NSE (neuron specific enolase) were significantly higher in all lung cancers vs BLD, reaching AUCs of 0.81 (95% CI 0.76-0.87), 0.78 (0.73-0.84), and 0.88 (0.84-0.93), respectively. By the three marker combination, the discrimination between benign and all malignant cases was improved resulting in an AUC of 0.93 (95% CI 0.90-0.96). In NSCLC vs. BLD, CYFRA 21-1, CEA and NSE were best discriminative STMs, with AUCs of 0.86 (95% CI 0.81-0.91), 0.80 (0.74-0.85), and 0.85 (0.79-0.91). The three marker combination also improved the AUC: 0.92; 95% CI 0.89-0.96). In SCLC vs. BLD, ProGRP (pro-gastrin-releasing peptide) and NSE were best discriminative STMs, with AUCs of 0.89 (95% CI 0.84-0.94) and 0.96 (0.93-0.98), respectively, and slightly improved AUC of 0.97 (95% CI 0.95-0.99) when in combination. Finally, discrimination between SCLC and NSCLC was possible by ProGRP (AUC 0.86; 95% CI 0.81-0.91), NSE (AUC 0.83; 0.78-0.88) and CYFRA 21-1 (AUC 0.69; 0.64-0.75) and by the combination of the 3 STMs (AUC 0.93; 0.91-0.96), with a sensitivity of 88% at 90% specificity. The results confirm the power of STM combinations for the differential diagnosis of lung cancer from benign lesions and between histological lung cancer subtypes.

Value of combined serum CEA, CA72-4, and CA19-9 marker detection in diagnosis of colorectal cancer.

The aim of this study was to examine whether the combination of serum tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen [CA]72-4, CA19-9) improves sensitivity and accuracy in the diagnosis of colorectal cancer and precancerous lesion tubular adenoma. An automatic electrochemiluminescence immunoassay with matched kits (ECLIA) was performed on a Roche Cobas e411 analyzer to determine the levels of serum CEA, CA72-4, and CA19-9 in 35 patients with early colorectal cancer, 87 patients with tubular adenoma, and 58healthy people undergoing colonoscopy after positive fecal immunochemical test (FIT) in a colorectal cancer screening program 2021 January to April. The values of these three tumor markers in the diagnosis of colorectal cancer and tubular adenoma were analyzed. 180 patients (92 female and 88 male) were included into the study. We compared serum CEA, CA72-4 and CA19-9 markers among 3 groups: healthy people (mean age 64,0 ±8,6), patients with tubular adenoma (mean age 62,7 ± 6,4) and colorectal cancer (mean age 59,2 ±6,2). The levels of serum CEA, CA72-4, and CA19-9 were higher in the colorectal cancer group than in the tubular adenoma group and healthy subjects, and these differences were significant (p < 0.05). The combination of CEA, CA72-4, and CA19-9had a higher diagnostic value for colorectal cancer compared to single markers, and the positive detection rate was 54.3%. The diagnostic power when using all three markers was the best, and applied for colorectal cancer and tubular adenoma. The combination of CA72-4, CEA, and CA19-9 markers increases the sensitivity and accuracy in the diagnosis of colorectal cancer and can thus be considered an important tool for early colorectal diagnosis.

A comparative study of tumor markers and dynamic contrast-enhanced CT and their combined evaluation in the diagnosis of renal cancer patients

The objectives of this study were to investigate the diagnostic efficacy of dynamic contrast-enhanced Computed Tomography (CT) and tumor markers and their combined evaluation in renal cancer patients. A total of eighty male patients with solid renal lesions were selected from our hospital and categorized into two groups based on pathological examination findings: renal cancer group and benign lesion group. A comparison was made between the findings of dynamic contrast-enhanced CT and tumor markers and the diagnostic efficacy of either mono or combined evaluation were compared. Receiver operating characteristic curves were plotted to better analyze and compare different diagnostic techniques. The serum concentrations of carcinoembryonic antigen (CEA), Cytokeratin 19 fragment (CYFRA21-1), midkine (MK) and matrix metalloproteinase 9 (MMP-9) in renal cancer patients were significantly higher than those with benign lesions (p &lt; 0.05). The Receiver Operating Characteristic (ROC) curve analysis demonstrated that the combination of dynamic contrast-enhanced CT and tumor markers had the highest area under the curve. This difference was statistically significant (p &lt; 0.05). The analysis of the overall model quality results revealed that the model values for both single and combination indicators exceeded 0.5, with the combined indicators having the highest value of (0.84). The diagnostic efficacy of dynamic contrast-enhanced CT combined with tumor markers for renal cancer is significantly higher than either the dynamic contrast-enhanced CT or tumor markers alone. The combination of dynamic contrast-enhanced CT and tumor markers has a significant therapeutic benefit in diagnosing renal cancer. We envisage that, this approach can offer valuable guidance for the clinical diagnosis and treatment of renal cancer.

Effectiveness of D-dimer in predicting distant metastasis in colorectal cancer.

Patients with cancer often present with a hypercoagulable state, which is closely associated with tumor progression. The purpose of this study was to assess the diagnostic efficacy of D-dimer in predicting distant metastasis in colorectal cancer (CRC). This study included 529 patients diagnosed with CRC at our hospital between January 2020 and December 2022. Plasma coagulation indicators and tumor markers were collected prior to treatment and their diagnostic efficacy for predicting CRC metastasis was assessed by receiver operating characteristic (ROC) curves. Independent risk factors for evaluating tumor metastasis were obtained by multivariate logistic regression analysis. The level of D-dimer in the metastatic group was significantly higher than that in the non-metastatic group (P<0.001). The results of the multiple logistic regression analysis indicated that lower level of prealbumin and platelet, and higher level of glucose, CEA and D-dimer were independent risk factors for distant metastasis in patients with CRC (P<0.05, respectively). The combination of prealbumin, glucose, D-dimer, platelet and tumor markers (PRE2) was found to be significantly more effective in predicting metastasis of CRC when compared to the combination of tumor marker alone (PRE1, P<0.001). Plasma D-dimer may be a novel tumor marker for screening metastases of CRC.

Predictive efficacy of combined tumor markers and gastrin for recurrence after endoscopic submucosal dissection in early gastric cancer patients.

This study aims to evaluate the predictive value of tumor markers combined with gastrin for tumor recurrence after endoscopic submucosal dissection (ESD) in patients with early gastric cancer. The clinicopathological data of 169 patients with early gastric cancer treated with ESD between March 2019 and January 2021 were retrospectively analyzed. The patients were divided into a relapse group (n=45) and a non-recurrence group (n=124). Clinical data such as carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), gastrin 17, pepsinogen I and pepsinogen II, as well as tumor size and degree of infiltration were examined to construct a recurrence prediction model using lasso regression. The comprehensive model showed superior predictive power (AUC=0.958, C-index=0.966) over biomarker-only models (AUC=0.925), indicating a significant improvement in the prediction of recurrence risk. Decision curve analysis confirmed the clinical utility of the model with a maximum net benefit of 73.37%. Key indicators such as CEA, CA19-9, AFP, gastrin 17 and pepsinogens I and II were statistically significant in predicting recurrence with P values < 0.01. The comprehensive model combining tumor markers with clinical data provides a more accurate and clinically valuable tool for predicting recurrence in early gastric cancer patients after ESD. This approach facilitates personalized risk assessment and may significantly improve prognostic management, emphasizing the importance of a multifaceted strategy in the management of early gastric cancer.

Clinical Value of Seven Autoantibodies Against Tumor-Associated Antigens and Tumor Markers in Lung Cancer Patients: A Retrospective Analysis from a Single Institution.

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.

Comparative role of tumor marker CA 242 and CA 19.9 in various pancreatic lesions

The pancreas has important endocrine and exocrine function and diseases of it causes significant morbidity and mortality. Diseases of the pancreas thus remain a continuing source of frustration in modern medicine. Clinical parameters have their limitations in diagnosing such lesions. Radiological evaluation also helps in diagnosing these lesions but to a certain extent. A good tumor marker is the answer to these problems. There are two tumor markers CA 242 and CA 19.9 which will not only help in early diagnosis of various pancreatic lesions, but also in differentiating them into neoplastic &amp; non-neoplastic lesions. 100 patients of various pancreatic lesions were evaluated prospectively having USG confirmed pancreatic lesions, unexplained pancreatitis, pancreatic mass or pancreatic cystic lesion or worrisome clinical, imaging (CECT/USG) or laboratory findings.Serum tumor marker CA 242 is more specific (100%) than CA 19.9(75%) and CA 19.9(71.9%) is more sensitive than CA 242(70.1%) in patients of various pancreatic lesions. While combined serum tumor marker CA 19.9 and CA 242 was more sensitive (70.5%) and specific (100%) than CA 19.9 and CA 242 alone. For detection of various pancreatic lesions by serum tumor marker CA 19.9 and CA 242, the sensitivity, specificity and positive predictive value increases if markers are used in combination (serum tumor marker CA 19.9 and CA 242).

Discovery and preliminary validation of a new panel of personalized ovarian cancer biomarkers for individualized detection of recurrence

Background: Following first-line treatment, over 80% of advanced ovarian cancer cases suffer recurrence. Treatment of patients with recurrence based on CA125 has not resulted in improvements in outcome postulating that we need biomarkers for earlier detection. A tumor-specific array of serum proteins with advanced proteomic methods could identify personalized marker signatures that detect relapse at a point where early intervention may improve outcome. Methods: For our discovery phase, we employed the proximity extension assay (PEA) to simultaneously measure 1,104 proteins in 120 longitudinal serum samples (30 ovarian cancer patients). For our validation phase, we used PEAs to concurrently measure 644 proteins (including 21 previously identified candidates, plus CA125 and HE4) in 234 independent, longitudinal serum samples (39 ovarian cancer patients). Results: We discovered 23 candidate personalized markers (plus CA125 and HE4), in which personalized combinations were informative of recurrence in 92% of patients. In our validation study, 21 candidates were each informative of recurrence in 3-35% of patients. Patient-centric analysis of 644 proteins generated a refined panel of 33 personalized tumor markers (included 18 validated candidates). The panel offered 91% sensitivity for identifying individualized marker combinations that were informative of recurrence. Conclusion: Tracking individualized combinations of tumor markers may offer high sensitivity for detecting recurrence early and aid in prompt clinical referral to imaging and treatment interventions.

Practical application of the CA-62 tumor marker in the initial diagnosis of oncological disease of epithelial origin: assistance to the doctor in interpreting the results

Aim. Demonstration the possibility of practical application of the highly sensitive tumor marker CA-62 in the initial diagnosis in asymptomatic patients with suspected cancer and/or the presence of pathological changes in instrumental studies, as well as describe the criteria for interpreting the results to help the doctor make a decision.&#x0D; Materials and methods. The article used the results and conclusions of blind clinical trials conducted to detect early stages of breast cancer (BC), prostate cancer (PC), colorectal cancer (CRC) and non-small cell lung cancer using the CA-62 tumor marker and other tumor markers. Statistical analysis was performed using the MedCalc program (MedCalc Software Ltd, Belgium). Diagnostic efficiency was assessed in terms of sensitivity, specificity, test accuracy, PPV and NPV, ROC analysis. The significance level was taken as p0.001.&#x0D; Results. The use of the standard cut-off value of 5000 U/ml of the CA-62 tumor marker makes it possible to achieve 97% sensitivity with 95% specificity in stage I BC. The combination of tumor markers CA-62 and CA 15-3 allows achieving 100% specificity in differentiation of BC and benign breast hyperplasia. The use of the CA-62 marker (6500 U/ml) in the gray zone of PSA 2.510 ng/ml improves the accuracy of detecting PC in biopsy from 35 to 93.1% with 90% sensitivity and 97% specificity. The use of a combination of tumor markers (CA-625000 U/ml, CYFRA 21-12.5 ng/ml and CEA5 ng/ml) will allow the doctor to improve the efficiency of differentiating lung cancer from chronic obstructive pulmonary disease. The combined use of markers (CEA3.5 ng/ml) and (CA-625000 U/ml) achieves 100% specificity with 97% sensitivity in detecting early stages of CRC.&#x0D; Conclusion. The article shows the possibilities of using the CA-62 marker, as well as new algorithms for the detection and differentiation of early stages of BC, PC, non-small cell lung cancer and CRC and benign neoplasms using the CA-62 marker in primary diagnosis. The use of the CA-62 tumor marker or its combination with other diagnostic methods can be a useful strategy for a comprehensive assessment of the risk of malignant neoplasms and increasing the diagnostic sensitivity of detecting early stages of cancer.

Identifying tumor markers-stratified subtypes (CA-125/CA19-9/carcinoembryonic antigen) in cervical adenocarcinoma.

There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma. A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA-IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models. Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes). Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.

The Diagnosis of Malignant Pleural Effusion Using Tumor-Marker Combinations: A Cost-Effectiveness Analysis Based on a Stacking Model.

By incorporating the cost of multiple tumor-marker tests, this work aims to comprehensively evaluate the financial burden of patients and the accuracy of machine learning models in diagnosing malignant pleural effusion (MPE) using tumor-marker combinations. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, CA125, and CA15-3 were collected from pleural effusion (PE) and peripheral blood (PB) of 319 patients with pleural effusion. A stacked ensemble (stacking) model based on five machine learning models was utilized to evaluate the diagnostic accuracy of tumor markers. We evaluated the discriminatory accuracy of various tumor-marker combinations using the area under the curve (AUC), sensitivity, and specificity. To evaluate the cost-effectiveness of different tumor-marker combinations, a comprehensive score (C-score) with a tuning parameter w was proposed. In most scenarios, the stacking model outperformed the five individual machine learning models in terms of AUC. Among the eight tumor markers, the CEA in PE (PE.CEA) showed the best AUC of 0.902. Among all tumor-marker combinations, the PE.CA19-9 + PE.CA15-3 + PE.CEA + PB.CEA combination (C9 combination) achieved the highest AUC of 0.946. When w puts more weight on the cost, the highest C-score was achieved with the single PE.CEA marker. As w puts over 0.8 weight on AUC, the C-score favored diagnostic models with more expensive tumor-marker combinations. Specifically, when w was set to 0.99, the C9 combination achieved the best C-score. The stacking diagnostic model using PE.CEA is a relatively accurate and affordable choice in diagnosing MPE for patients without medical insurance or in a low economic level. The stacking model using the combination PE.CA19-9 + PE.CA15-3 + PE.CEA + PB.CEA is the most accurate diagnostic model and the best choice for patients without an economic burden. From a cost-effectiveness perspective, the stacking diagnostic model with PE.CA19-9 + PE.CA15-3 + PE.CEA combination is particularly recommended, as it gains the best trade-off between the low cost and high effectiveness.

Combinations of plasma cfDNA concentration, integrity and tumor markers are promising biomarkers for early diagnosis of non-small cell lung cancer

BackgroundCirculating cell-free DNA (cfDNA) concentration and integrity as noninvasive biomarkers play an important role in cancer diagnosis, prognosis and therapy monitoring. However, few studies have been conducted on the combination of plasma cfDNA concentration, integrity and tumor markers (CEA, CA125, NSE and CYFRA21-1) for cancer detection. Thus, the purpose of this study was to investigate the diagnostic value of combining plasma cfDNA concentration, integrity and tumor markers in early detection of non-small cell lung cancer (NSCLC). MethodsPlasma cfDNA concentration from 50 healthy controls and 84 NSCLC patients were assessed by quantitative real-time PCR of ALU repeated sequence. Plasma cfDNA integrity was calculated as the ratio of long to short fragments (ALU115/60). ResultsPlasma cfDNA concentration (ALU60 and ALU115) and integrity ALU115/60 were significantly higher in NSCLC patients with stage III/IV than in healthy controls (p = 0.0002, p < 0.0001, and p = 0.0093, respectively). The receiver operating characteristic (ROC) curve for discriminating NSCLC patients from healthy controls had an area under the curve (AUC) of 0.936 (95 % CI, 0.939–0.996). Moreover, the combination of plasma cfDNA concentration, integrity and tumor markers (CEA, CA125, NSE and CYFRA21-1) had higher diagnostic performance than either plasma cfDNA concentration alone, integrity alone or tumor markers alone, with sensitivity, specificity and AUC value of 94.05%, 90.00% and 0.968, respectively. These results demonstrated that the combination of plasma cfDNA concentration, integrity and tumor markers could significantly improve the diagnostic accuracy of NSCLC. ConclusionCombination of plasma cfDNA concentration, integrity and tumor markers is a promising biomarker for early diagnosis of NSCLC.

Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality.

The effect of a single tumor marker on the prognosis of gastric cancer patients is not ideal. This study explored a novel prognostic assessment method for gastric cancer (GC) patients using a combination of three important tumor markers (CEA, CA72-4, and CA19-9). Data from 1966 GC patients who underwent curative gastrectomy at Sun Yat-Sen University Cancer Center (Guangzhou, China) were included. Hazard ratios (HR) for all factors for overall survival (OS) were analyzed by Cox regression. A nomogram and calibration curve were used to establish the survival prediction model. The prediction accuracy was evaluated with the concordance index (C-index). All patients were divided into four groups (C0-C3) according to the number of elevated tumor markers. The 5-year OS rates of the patients in preoperative groups C0-C3 were 83.8% (81.3-86.4%), 72.8% (68.5-77.4%), 58.9% (50.4-68.9%), and 18.5% (4.0-33.0%), respectively, and those in postoperative groups C0-C3 were 82.1% (79.4-84.8%), 76.1% (72.2-80.3%), 57.6% (48.4-68.5%), and 16.8% (5.1-28.5%), respectively, with significant differences between each C0-C3 subgroup in both preoperative and postoperative cohorts. Multivariate analysis showed that preoperative (HR: 6.001, 95% CI: 3.523-10.221) and postoperative (HR: 8.149, 95% CI: 4.962-13.528) elevated tumor markers were independent risk factors for GC patients. The C-index for the combined use of tumor markers was 0.65-0.66, which was higher than that for using a single tumor marker (0.53-0.56). The combined use of tumor markers significantly improved the prognostic value compared with using a single tumor marker. The survival prediction model including the combined tumor markers was accurate and effective.