A nomogram based on glycomic biomarkers in serum and clinicopathological characteristics for evaluating the risk of peritoneal metastasis in gastric cancer.
ABSTRACT: Background:Peritoneal metastasis (PM) in gastric cancer (GC) remains an untreatable disease, and is difficult to diagnose preoperatively. Here, we aim to establish a novel prediction model. Methods:The clinicopathologic characteristics of a cohort that included 86 non-metastatic GC patients and 43 PMGC patients from Zhongshan Hospital were retrospectively analysed to identify PM associated variables. Additionally, mass spectrometry and glycomic analysis were applied in the same cohort to find glycomic biomarkers in serum for the diagnosis of PM. A nomogram was established based on the associations between potential risk variables and PM. Results:Overexpression of 4 N-glycans (H6N5L1E1: m/z 2620.93; H5N5F1E2: m/z 2650.98; H6N5E2, m/z 2666.96; H6N5L1E2, m/z 2940.08); weight loss???5 kg; tumour size???3 cm; signet ring cell or mucinous adenocarcinoma histology type; poor differentiation; diffuse or mixed Lauren classification; increased CA19-9, CA125, and CA724 levels; decreased lymphocyte count, haemoglobin, albumin, and pre-albumin levels were identified to be associated with PM. A nomogram that integrated with five independent risk factors (weight loss???5 kg, CA19-9???37 U/mL, CA125???35 U/mL, lymphocyte count?
Project description:<h4>Background</h4>Serum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.<h4>Methods</h4>In total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model.<h4>Results</h4>Pre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P?<?0.05), but only the change (diff-) of CA199 was related to prognosis (P?=?0.05). In the multivariable analysis, pre- (P?=?0.014) and post-CA724 (P?=?0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P?=?0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P?<?0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P?=?0.019), while pre-CA724 was not (P?=?0.082). However, AFU, AFP and CEA showed no association with survival (P?>?0.05).<h4>Conclusions</h4>CA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.
Project description:<h4>Objectives</h4>Associations between serum tumor biomarkers and human epidermal growth factor receptor 2 (HER2) overexpression among locally advanced gastric cancer patients were yet to be determined and therefore warranted investigation.<h4>Results</h4>A total of 318 patients were analyzed. The odds ratios of CA724 were 4.79 (95% CI 1.55-14.79) and 6.29 (1.40-28.19) in comparing the HER2 (2+/3+) and HER2 (3+) with the negative group, respectively (p < 0.05). A combination of the four biomarkers yielded slightly but not significantly greater areas under the curve (AUC = 0.83; 0.71-0.94) than that of serum CA724 alone (0.80; 0.68-0.91); however, an index generated from the combination had better diagnostic performance with 85.7% sensitivity, 80.4% specificity and 97.8% negative predictive value to predict the strong overexpression of HER2 (3+). CA199, CEA or CA125 alone was not associated with HER2 overexpression. Leave-one-out cross-validation found a consistent association between serum CA724 and HER2 (2+/3+) overexpression.<h4>Methods</h4>Patients undergoing radical gastrectomy from 8/2012 to 12/2013 and with pathological stage II-III gastric cancer were retrospectively analyzed. HER2 expression of the surgical samples was estimated using immunohistochemistry; serum CA724, CA199, CEA and CA125 were preoperatively tested. Internal validation was performed using the leave-one-out approach.<h4>Conclusions</h4>Serum CA724 is significantly associated with the overexpression of HER2 among locally advanced gastric cancer patients. The combination of CA724, CA199, CEA and CA125 is better than serum CA724 alone in predicting HER2 overexpression. External validation and further investigation of the biological mechanisms of these associations are required.
Project description:Background The present study was designed to verify the accuracy of the noninvasive biomarkers enolase/Cr, CA125, and CA19-9 as a clinical diagnostic tool for the detection of endometriosis. Methods A cross-sectional study was performed at Rasool-e-Akram Hospital affiliated to Iran University of Medical Sciences, Tehran, Iran, from April 2015 to April 2018. Eighty-six women were scheduled to undergo laparoscopy due to chronic pelvic pain, infertility, pelvic mass, and abnormal uterine bleeding. Serum and urine samples of all patients were collected preoperatively. Serum levels of CA125 and CA19-9, and urine levels of enolase-1 were measured. Serum levels of CA125 and CA19-9 were determined by the electrochemiluminescence method (ECL). Urinary enolase-1 was measured by the ELISA method. Result Serum levels of CA125 and CA19-9 were significantly higher in the endometriosis group than in controls (p < 0.001, p = 0.004, respectively). Levels of enolase I and enolase/Cr were higher in patients with endometriosis, but the differences were not statistically significant. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combined enolase/Cr, CA125, and CA19-9 were 65%, 66.6%, 71%, and 60.1%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of combined enolase/Cr, CA125, and CA19-9 was 1.94 and 0.52, respectively. The area under the ROC curve for enolase/Cr + CA125 + CA19 ? 9 was 0.675 (95% confidence interval 0.573-0.710). Conclusion The present study revealed that concurrent measurement of enolase-1, CA125, and CA19-9 might be a valuable noninvasive test for the identification of endometriosis.
Project description:The aim of the present study was to investigate the association between serum carbohydrate antigen (CA)19-9 and CA125 levels, and human epidermal growth factor receptor 2 (HER2) expression in patients with gastric cancer, as well as to identify any correlation between them and the risk of recurrence and metastasis. A total of 256 patients were enrolled in the present study, and 219 patients were followed-up to investigate recurrence and metastasis of gastric cancer. Immunohistochemistry was used to detect HER-2 in gastric adenocarcinoma and paracancerous tissues. The positive rate of CA19-9 and CA125 in stages III/IV was higher compared with that in stages I/II. The positive rate of HER2 in distinct stages of gastric cancer was not statistically different. Serum CA19-9 and CA125 were not associated with the positive expression of HER2. The recurrence and metastasis of CA19-9, CA125 and HER2-positive gastric cancer were increased compared with those experienced by CA19-9, CA125 and HER2-negative patients. Age, stage and preoperative tumor markers were associated with 3-year prognosis of gastric cancer. HER2 [odds ratio (OR)=2.55] and CA19-9 (OR=1.22) were independent prognostic factors in patients with gastric cancer. CA19-9, CA125 and HER2 may be used to predict the recurrence or metastasis of gastric cancer. The combined detection may be able to improve the sensitivity and efficiency of predicting the recurrence or metastasis of gastric cancer. Preoperative positive serum for CA19-9 and CA125 were associated with poor prognosis in patients with gastric cancer. CA19-9 and HER2 were independent prognostic factors of gastric cancer.
Project description:PURPOSE:Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1, and REG3A are present before clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. EXPERIMENTAL DESIGN:This nested case-control study within the UKCTOCS included 118 single and 143 serial serum samples from 154 postmenopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched noncancer controls. Samples were split randomly into independent training and test sets. CA19-9, CA125, CEACAM1, and REG3A were measured using ELISA and/or CLIA. Performance of markers to detect cancers at different times before diagnosis and for prognosis was evaluated. RESULTS:At 95% specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up to 2 years before diagnosis. Combining CA19-9 and CA125 improved sensitivity as CA125 was elevated (>30 U/mL) in approximately 20% of CA19-9-negative cases. CEACAM1 and REG3A were late markers adding little in combined models. Average lead times of 20 to 23 months were estimated for test-positive cases. Prediagnostic levels of CA19-9 and CA125 were associated with poor overall survival (HR, 2.69 and 3.15, respectively). CONCLUSIONS:CA19-9 and CA125 have encouraging sensitivity for detecting preclinical pancreatic cancer, and both markers can be used as prognostic tools. This work challenges the prevailing view that CA19-9 is upregulated late in the course of pancreatic cancer development.
Project description:Aims:Interstitial lung disease (ILD) is the most common type of pulmonary involvement of extraglandular complication in patients with primary Sjögren's syndrome (pSS), but the diagnosis of pSS-associated ILD (pSS-ILD) is still challenging. This study aimed to investigate the levels of serum tumor markers in pSS patients with or without ILD (pSS-non-ILD) and explore its diagnostic value for pSS-ILD. Methods:A total of 168 pSS-ILD patients and age- and sex-matched 538 pSS-non-ILD were recruited. The levels of peripheral tumor markers, including carbohydrate antigen (CA)153, CA125, CA19-9, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), ?-human chorionic gonadotropin, alpha fetoprotein, CA724, and complexed prostate specific antigen, the clinical manifestations, and general laboratory indicators were measured and collected. Results:Compared with pSS-non-ILD, pSS-ILD patients had higher levels of disease activity indicators, such as EULAR Sjögren's syndrome disease activity index, ESR, and CRP, and elevated serum levels of tumor markers: NSE, CEA, CA125, and CA153. The serum levels of CA153 [odds ratio (OR)?=?4.521, 95% confidence interval (CI)?=?[1.871, 10.928)] and CEA [OR?=?2.879, 95% CI?=?(1.305, 6.353)] were significantly correlated with the onset of SS-ILD. CA153 was the only tumor marker with area under receiver operating characteristic curve (AUC) over 0.7 [AUC?=?0.743, 95% CI?=?(0.70, 0.79)]. Conclusion:Tumor markers increased in serum of pSS-ILD patients. Higher CA153 levels are significantly correlated to the increased risk of ILD in patients with pSS and may be directly involved in the pathogenesis of pSS-ILD. Serum CA153 had the best diagnostic value in those tumor markers for pSS-ILD without malignancy.
Project description:Helicobacter pylori infection is a major cause of several cancers such as gastric, pancreatic and lung. The relationship between H. pylori and tumour markers continues to remain unclear. The primary goal of this study is to clarify the associations between H. pylori infection and six tumour markers (ie, carcinoembryonic antigen (CEA), cancer antigen (CA) 153, CA199, CA724, CA125 and alpha-fetoprotein (AFP)). The secondary goal is to provide understanding for further research about H. pylori infection and gastrointestinal cancer.Observational retrospective study.The study was performed in Beijing, China, where enrolled subjects had all passed health examinations during the period of 2012-2016. Subjects were categorised into H. pylori (+) and H. pylori (-) group according to their infection status and the measured six biomarkers. We used logistic regression models and generalised linear models to explore the associations between H. pylori infection and six tumour markers (ie, CEA, CA153, CA199, CA724, CA125 and AFP).A total of 14?689 subjects were included and 6493 (44.2%) subjects were infected by H. pylori. The subjects had a mean age (1SD) of 45 (18) years. There were 4530 (31.0%) female subjects.After adjusting for the confounding factors, infections with H. pylori were found to be significantly associated with abnormal ratios in CEA, AFP and CA724 of H. pylori (+) to H. pylori (-) groups. Significant positive correlation was found between H. pylori infection and CEA values (adjusted ?=0.056; 95%?CI 0.005 to 0.107; p=0.033).In this observational retrospective study, we observed the H. pylori infections in a Chinese population and found higher CEA level in H. pylori-infected subjects and abnormal ratios in CEA, AFP and CA724 in infected subjects to uninfected subjects. These findings may provide a basis for future exploration with H. pylori and tumour markers.
Project description:Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 (211 At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that 211 At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test ?-particle radioimmunotherapy with 211 At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of 211 At-trastuzumab (1 MBq) was a more efficient means of delivery of 211 At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of 211 At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA double-strand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered 211 At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with 211 At-trastuzumab may offer a new treatment option for HER2-positive PMGC.
Project description:<b>Background</b>: Peritoneal metastasis (PM) is the most common cause of death in gastric cancer (GC) patients. However, diagnosis of PM is still difficult in clinical practice. This study aimed to explore the diagnostic and prognostic value of digital rectal examination (DRE) in GC. <b>Methods</b>: 247 GC patients with PM confirmed by operation were included. The diagnostic yield of DRE compared with computed tomography (CT) was calculated. In another group of 1330 cases receiving radical gastrectomy, 38 cases with DRE (+) postoperatively were analyzed to identify risk factors. A nomogram was constructed to predict postoperative DRE (+). <b>Results</b>: The specificity, positive predictive value and positive likelihood ratio of DRE in diagnosis of PM was 99.8%, 91.2% and 58.4, higher than CT (97.6%, 64.9% and 10.4). Though the sensitivity of DRE (12.6%) was lower than CT (24.7%), 17 of 31 patients with DRE (+) could not be found by CT. Moreover, the overall survival of confirmed PM patients with DRE (+) (PM-DRE (+)) was much lower than PM-DRE (-) patients (P<0.001). In addition, the nomogram to predict postoperative DRE (+) had a bootstrap-corrected concordance index of 0.73 and was well calibrated. <b>Conclusions</b>: GC patients with DRE (+) could be regarded as a special subtype of stage IV ones with poorer prognosis. Supply of palliative care and chemotherapy rather than unnecessary operation might be a better alternative for these patients. DRE was an effective supplement for CT and should be generally recommended for GC patients.
Project description:Objective: The aim of this study is to evaluate whether radiomics imaging signatures based on computed tomography (CT) could predict peritoneal metastasis (PM) in gastric cancer (GC) and to develop a nomogram for preoperative prediction of PM status. Methods: We collected CT images of pathological T4 gastric cancer in 955 consecutive patients of two cancer centers to analyze the radiomics features retrospectively and then developed and validated the prediction model built from 292 quantitative image features in the training cohort and two validation cohorts. Lasso regression model was applied for selecting feature and constructing radiomics signature. Predicting model was developed by multivariable logistic regression analysis. Radiomics nomogram was developed by the incorporation of radiomics signature and clinical T and N stage. Calibration, discrimination, and clinical usefulness were used to evaluate the performance of the nomogram. Results: In training and validation cohorts, PM status was associated with the radiomics signature significantly. It was found that the radiomics signature was an independent predictor for peritoneal metastasis in multivariable logistic analysis. For training and internal and external validation cohorts, the area under the receiver operating characteristic curves (AUCs) of radiomics signature for predicting PM were 0.751 (95%CI, 0.703-0.799), 0.802 (95%CI, 0.691-0.912), and 0.745 (95%CI, 0.683-0.806), respectively. Furthermore, for training and internal and external validation cohorts, the AUCs of radiomics nomogram for predicting PM were 0.792 (95%CI, 0.748-0.836), 0.870 (95%CI, 0.795-0.946), and 0.815 (95%CI, 0.763-0.867), respectively. Conclusions: CT-based radiomics signature could predict peritoneal metastasis, and the radiomics nomogram can make a meaningful contribution for predicting PM status in GC patient preoperatively.