Serum Carbohydrate Antigen Research Articles

Assessment of long noncoding RNA CCAT1 using real time-polymerase chain reaction in colorectal cancer patients

Colorectal cancer (CRC) is linked to high mortality, mainly when discovered in its advanced stages. Several studies have pointed to the role of epigenetic factors in CRC and other cancers. Long non-coding RNAs (lncRNAs) are involved in the initiation, progression, metastasis, and modulation of the response to chemotherapeutic modalities of CRC as vital contributors to epigenetic mechanisms. Colon cancer-associated transcript-1 (CCAT1) is one of the lncRNAs that have been dysregulated in serum samples, providing a non-invasive route for diagnosing CRC patients. This study aimed to determine the role of CCAT1 expression as diagnostic and prognostic markers. We tested the associations of CCAT1 expression with serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). The study included three groups: 41 patients with colorectal cancer, 39 patients with precancerous benign colorectal diseases, and 20 normal control individuals. CEA and CA 19-9 were measured by an immunoassay automated system. The expression level of CCAT1 was assessed by a real-time polymerase chain reaction. There was a statistically significant elevation of serum CEA levels in patients with CRC compared to patients with precancerous benign colorectal diseases. Furthermore, there was no statistically significant difference in serum CA 19-9 levels between all groups (p = 0.102). Interestingly, CCAT1 expression was significantly upregulated in the blood of CRC patients compared to the precancerous benign colorectal diseases group (p = 0.009) and the control group (p<0.001). Also, expression of CCAT1 was significantly elevated in patients with precancerous benign colorectal diseases compared to the control group (p=0.004). In conclusion, measuring the expression level of CCAT1 is more advised than assessment of CEA and CA 19-9 for the early diagnosis and prognosis of colorectal cancer.

Different Tumour Marker Kinetics as Prognosticators in Patients with Adenocarcinoma of Gall Bladder Undergoing Chemotherapy: A Cohort Study

Introduction: Gallbladder Cancer (GBC) is the most common malignancy of the biliary tract worldwide. Patients do not have specific symptoms, and therefore, GBC is usually diagnosed at an advanced stage. Carbohydrate Antigen (CA)-242, CA 19-9, and Cancer Antigen 125 (CA-125) have been found to be effective in the diagnosis and prognosis of GBC. Aim: To determine the significance of tumour markers as prognosticators in adenocarcinoma of GBC with chemotherapy. Materials and Methods: The present cohort study was conducted in the Department of Biochemistry, Murshidabad Medical College and Hospital, Baharampur, West Bengal, India, between December 2021 and November 2022. Thirty patients with pathologically confirmed adenocarcinoma of the gallbladder who were treated with gemcitabine-based chemotherapy were included in the study. Differences in serum CA-125 and CA 19-9 levels before and after chemotherapy (KINETICS) were measured along with haemoglobin, serum urea, creatinine, total bilirubin and Neutrophil-Lymphocyte Ratio (NLR). Receiver Operating Characteristic (ROC) curve analysis and Kaplan-Meier analyses of CA-125, CA 19-9, and combined changes were performed to assess survival rates and their statistical relevance as prognosticators in correlation with disease progression. Results: The mean±Standard Deviation (SD) age was 52.4±5.275 years. A total of 25 (83.3%) patients were females. The associations of CA 19-9 change with other baseline variables were analysed, and there were significant associations with baseline Carbohydrate Antigen (CA19-9) levels (p-value=0.003) and metastatic changes (p-value <0.001). Patients with decreased tumour markers had significantly better Progression- Free Survival (PFS) than patients with increased tumour markers. The pre- and post-chemotherapy CA 19-9 ratio had the highest area-under-the-curve values (AUC 0.910) for predicting 6-month PFS, whereas for predicting metastatic changes, the combined pre- and post-chemotherapy marker ratio had the highest AUC 0.842. In the multivariate analysis, CA 19-9 ≥100 U/mL at diagnosis (p-value <0.001) and NLRchange ≥1.0 (p-value=0.003) were independent prognosticators of PFS, with hazard ratios of 1.007 (p-value <0.001) and 15.4 (p-value=0.003), respectively. Conclusion: CA 19-9 kinetics proved to be a reliable prognosticator of metastatic changes in patients with adenocarcinoma of the gallbladder undergoing chemotherapy. The significant decline in tumour markers that were seen throughout the follow-up phase emphasises how important it is to use these markers as primary indicators of treatment response. To validate the present study findings, larger-scale studies involving a longer follow-up period and a greater number of patients are needed.

A survival nomogram involving nutritional-inflammatory indicators for cervical cancer patients receiving adjuvant radiotherapy.

Objective: The combined impact of nutritional and inflammatory status on survival of cervical cancer patients remained unclear. This study aimed to construct a survival nomogram involving both nutritional and inflammatory indicators and evaluate their potential correlation. Methods: This retrospective study included 325 cervical cancer patients who received adjuvant radiotherapy between September 2010 and September 2020. Baseline nutritional indicators such as body mass index (BMI), controlling nutritional status (CONUT) and serum albumin were assessed. Inflammatory indicators of platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), systemic immune inflammation index (SII) and system inflammation response index (SIRI) were evaluated respectively. The LASSO regression and Cox regression models were applied for variable selection and nomogram building. The predictive accuracy and superiority of prognostic model were assessed by area under curve (AUC), C-index, decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Results: Patients with high inflammatory indicators (PLR, NLR and SII) and poor nutritional status (CONUT scores > 2) suffered poorer prognosis compared to these with well nutritional status and lower inflammation levels. Our study unveiled a positive correlation between malnutrition and hyperinflammation. Even after accounting for baseline inflammatory level, malnutrition remained a significant risk factor for patients. Notably, the inflammatory level and nutritional status were further modulated by the clinical features of patients. Patients with poorer nutritional status exhibited higher levels of PLR, NLR, SII and SIRI, particularly for those in advanced clinical stages and with non-squamous cell carcinoma. In addition, our study found elevated levels of circulating basophil and serum carbohydrate antigen 125 (CA125) were associated with the poor prognosis. The prognostic nomogram which incorporated the nutritional-inflammatory indicators of PLR and CONUT showed a favorable performance with the AUC value of 0.76 at 5-year survival prediction. The DCA, IDI and NRI consistently demonstrated the favorable superiority of the model. Moreover, the nomogram-based risk stratification system could effectively classify patients into three mortality risks subgroups. Conclusions: Poorer nutritional and high inflammatory status collectively contributed to the poorer prognosis. The prognostic nomogram which incorporated nutritional-inflammatory indicators significantly improved the prediction of long-term outcomes of cervical cancer patients undergoing adjuvant radiotherapy.

Distinct clinical characteristics in stage III rectal cancer among different age groups and treatment outcomes after neoadjuvant chemoradiotherapy.

There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem. We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies. This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old). There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633-4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720-5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102-4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145-4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113-2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150-3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745-4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282-3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS (p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS (p = 0.006, p = 0.018, p = 0.006, respectively). In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma.

Primary hepatic carcinoma (PHC) has an insidious onset and is usually diagnosed in the middle and late stages. Although transcatheter arterial chemoembolization (TACE) is the preferred option for treating middle- and advanced-stage PHC, it has limited efficacy in killing tumor cells and poor long-term efficacy. TACE plus percutaneous microwave coagulation therapy (PMCT) is more effective than interventional therapy alone and can improve survival time. However, there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC. To investigate the effect of PMCT + TACE on serum tumor markers and the prognosis of middle-late PHC. This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People's Hospital between March 2018 and February 2021. Patients were divided into a single group (treated with TACE, n = 75) and a combined group (treated with TACE + PMCT, n = 75). Before and after treatment, the clinical efficacy and serum tumor marker levels [carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA)] of both groups were observed. The 1-year survival rates and prognostic factors of the two groups were analyzed. The combined group had 21 and 35 cases of complete remission (CR) and partial remission (PR), respectively. The single group had 13 and 25 cases of CR and PR, respectively. After 4 wk of treatment, the serum CA19-9, CEA, and AFP levels in the single and combined groups decreased, with the decrease in the combined group being more significant (P < 0.05). The 1-year survival rate of the combined group (80.00%) was higher than that of the single group (60.00%) (P < 0.05). The average survival time within 1 year in the combined group was 299.38 ± 61.13 d, longer than that in the single group (214.41 ± 72.97 d, P < 0.05). COX analysis revealed that tumor diameter, tumor number, and the treatment method were prognostic factors for patients with middle-late PHC (P < 0.05). TACE + PMCT is effective in treating patients with mid-late PHC. It reduces the levels of tumor markers, prolongs survival, and improves prognosis.

The Clinical Implications of Serum Carbohydrate Antigen 19-9 Levels in Patients with Nontuberculous Mycobacteria Pulmonary Disease.

Serum carbohydrate antigen 19-9 (CA19-9) levels can increase in nontuberculous mycobacteria pulmonary disease (NTM-PD), and the levels correlate with disease activity. We compared the clinical characteristics of NTM-PD patients with and without elevated CA19-9 levels and evaluated its association with antibiotic response in a retrospective study of NTM-PD patients diagnosed between January 1994 and December 2020. We analyzed 1112 patients who had serum CA19-9 measured: 322 with elevated CA19-9 and 790 with normal CA19-9. The erythrocyte sedimentation rate and C-reactive protein levels were significantly higher in the elevated CA19-9 group (p < 0.001 and p = 0.029, respectively). The 1-year culture conversion rate after antibiotics did not differ between the elevated (n = 206) and normal (n = 377) CA19-9 groups (80% vs. 72%, p = 0.055). Analysis of a subset of 434 patients revealed that current smoking, bronchiectasis, acid-fast bacilli smear positivity, and the M. abscessus strain significantly reduced microbiological cure rates. Serum CA 19-9 levels did not have a significant association with microbiological cure in a multivariate analysis. These findings suggest that the role of serum CA19-9 in predicting antibiotic treatment outcomes is limited, and that elevated CA19-9 does not necessarily indicate a poor outcome.

Analysis of risk factors associated with distant metastasis detected at laparotomy in patients with radiologically resectable pancreatic ductal adenocarcinoma

AbstractPurposeThis study aimed to evaluate the preoperative risk factors in patients with radiologically resectable pancreatic ductal adenocarcinomas (PDACs), deemed to be unresectable intraoperatively.MethodsData on patients radiologically diagnosed with resectable PDACs and subsequently underwent pancreatectomy between January 2020 and December 2021 were retrospectively collected. Preoperative risk factors were also analysed.ResultsFifty‐three patients with resectable PDAC who underwent laparotomy for curative intent were divided into the no‐metastases (n = 32) and distant metastases (n = 21) groups. Univariate analysis identified factors associated with distant metastases found intraoperatively, such as significant weight loss (odds ratio [OR] 5.29, P = .02), tumour size &gt;35 mm (OR 4.15, P = .017), tumours located at the body and tail of the pancreas (OR 6, P = .041), superior mesenteric vein (SMV) abutment from the tumour (OR 7.5, P = .02), serum carbohydrate antigen 19‐9 &gt; 385 IU/mL (OR 3.58, P = .031) and serum carcinoembryonic antigen (CEA) levels &gt;9 IU/mL. However, multivariate analysis showed that only significant weight loss (adjusted OR 27.19, P = .011), SMV abutment from the tumour (adjusted OR 52.64, P = .01) and serum CEA levels &gt;9 IU/mL were associated with distant metastases found intraoperatively.ConclusionSignificant weight loss, SMV abutment and serum CEA levels of &gt;9 IU/mL were intraoperatively associated with distant metastases. Staging laparoscopy and positron emission tomography–computed tomography may reduce unnecessary laparotomies and change clinical management in these patients.

Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis.

Obstructive sleep apnea syndrome (OSAS) combined with heart failure (HF) has become a serious disease that threatens human health. Therapeutic interventions targeting OSAS have been shown to improve outcomes in patients with HF, so the identification of severe OSAS in HF is critical. Carbohydrate antigen 125 (CA125) is associated with inflammation and volume overload. The levels of CA125 are elevated in the serum of patients with HF and might be further elevated in patients with HF and OSAS. The aim of this study was to measure CA125 levels in patients with HF with and without OSAS and to analyze affecting factors. In this single-center retrospective cohort study, a total of 95 patients diagnosed with HF hospitalized in Zhongda Hospital from April 2021 to April 2022 were recruited, including 55 patients with OSAS and 40 patients without OSAS. Participants with a history of central sleep apnea syndrome, severe chronic obstructive pulmonary disease, tumors, severe infection, or who were pregnant were excluded. The histories of the participants were recorded, and laboratory examinations were performed. Binary logistic regression analysis was performed to determine the relationship between serum CA125 levels and OSAS in patients with HF. The serum CA125 levels were higher in the HF + OSAS group than in the HF group (29.60 vs. 9.68 U/mL, P<0.001). According to the univariate analysis, CA125 (>35 U/mL) was significantly related to pleural effusion, acute HF, apnea-hypopnea index (AHI), left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Finally, the AHI demonstrated statistical significance in multiple analyses (OR 1.070, 95% CI: 1.019-1.124, P=0.006). Spearman rank correlation coefficient analysis showed that CA125 was positively correlated with AHI, and Ln(CA125) (Ln is the natural logarithm based on e) gradually increased with increasing AHI (r=0.551, P<0.0001). The levels of CA125 were further increased in patients with HF and OSAS, and CA125 (>35 U/mL) was positively correlated with AHI. As a biomarker associated with inflammation and congestion, serum CA125 may have certain value in the diagnosis of patients with HF combined with OSAS.

Diagnostic value of the combination of circulating serum miRNAs and CA125 in endometriosis.

Circulating microRNAs (miRNAs) can serve as noninvasive biomarkers for endometriosis, but their diagnostic and prognostic values require investigation. This study evaluated the potential of 6 miRNAs in diagnosing endometriosis and predicting fertility. The study included patients with endometriosis (stages I-IV) and controls admitted to Sun Yat-Sen Memorial Hospital between May 2013 and March 2014. The serum expression levels of 6 miRNAs (miR-199a, miR-145*, miR-122, miR-9*, miR-141*, and miR-542-3p) were determined using qRT-PCR. Receiver operating characteristics curves were used to determine the diagnostic accuracy. The study included 155 patients with endometriosis and 77 controls. The model combining miR-199a, miR-122, miR-145*, and miR-141* with the carbohydrate antigen 125 (CA125) exhibited 81.8% sensitivity and 92.6% specificity and an area under the curve of 0.939 for diagnosing endometriosis. When combining miR-199a, miR-122, miR-145*, miR-542-3p, and CA125, the receiver operating characteristics curve showed an area under the curve of 0.759 and 79.6% sensitivity and 73.5% specificity for stage I/II versus III/IV endometriosis. Circulating miRNA levels were associated with pelvic adhesions (miR-199a, P < .05), lesion distribution (miR-9*, miR-145*, and miR-141*; all P < .05), and the presence of deep infiltrating endometriosis (miR-199a and miR-122; both P < .001). The expression levels of miR-199a, miR-122, and miR-542-3p decreased with an increasing endometriosis fertility index. The model combining circulating miRNAs (miR-199a, miR-122, miR-145*, and miR-141*) and CA125 is promising for diagnosing endometriosis and its severity. miR-199a, miR-122, and miR-542-3p were associated with the endometriosis fertility index and might be used to predict fertility preoperatively, but these results require confirmation.

The real-world study of the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer in China

Objective: Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods: A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results: The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion: This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

Association of elevated serum carbohydrate antigen 19-9 levels with extensive interstitial lung disease in patients with systemic sclerosis: A cross-sectional study.

To assess the usefulness of carbohydrate antigen 19-9 (CA19-9) as a biomarker for systemic sclerosis-associated interstitial lung disease (SSc-ILD), using serum samples and clinical parameters of patients with SSc. Patients with SSc admitted to Tokyo Women's Medical University Hospital between 2010 and 2021 and those who underwent chest computed tomography (CT) were included. Patients were diagnosed with ILD based on chest CT findings, and SSc-ILD was categorized as either a limited or extensive disease based on chest CT and pulmonary function test findings. Serum CA19-9 levels were measured in 56 patients with SSc and in 32 healthy individuals. Additionally, we evaluated the difference in serum CA19-9 levels between the groups, the correlation with ILD area and pulmonary function, and discriminative performance to diagnose extensive ILD. Of the 56 patients with SSc, 40 (71.4%) had ILD, and 17 (30.4%) were classified as having extensive disease. Serum CA19-9 levels were significantly elevated in patients with extensive disease compared to those with limited disease (median [interquartile range]: 25.7 U/mL [10.1-50.8] vs. 8.8 U/mL [4.5-17.6], p = .02) and correlated with ILD area (r = .30, p = .02). There was no significant correlation between serum CA19-9 level and pulmonary function. The cutoff of CA19-9 for the diagnosis of the extensive disease was determined to be 19.8 U/mL, with a sensitivity of 64% and specificity of 82% and an area under the curve of 0.74 (95% confidence interval 0.58-0.90). The serum CA19-9 level may be a useful marker for identifying patients with SSc-ILD with extensive disease.

The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer.

This study aimed to explore the value of color Doppler ultrasonography combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in differential diagnosis of gastric stromal tumor (GST) and gastric cancer (GC). An analysis of the clinical data of 180 patients with clinically suspected gastric space occupying lesions. According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97). Color Doppler ultrasonography, serum tumor markers CEA and CA19-9 were compared. The research results showed that serum CEA and CA19-9 levels were lower in patients with GST group than those with GC group (both P < 0.001). With postoperative pathology as the gold standard, detection rates of GST and GC by combination of color Doppler ultrasound (CDUS), serum CEA, and CA19-9 were higher than those of each index alone (both P < 0.001). There was no difference between detection rates of GST and GC by combination of CDUS, serum CEA, and CA19-9 (P = 0.058). Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which may provide a reliable reference basis for clinical diagnosis and treatment.

Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma

BackgroundChanges in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. MethodsThis was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. ResultsAmong 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. ConclusionIn patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.

Association of CA-125 with markers of congestion, and effect of empagliflozin on CA-125 in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalisation and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on carbohydrate antigen 125 (CA-125) are uncertain. CA-125 has a potential role in HFrEF in the assessment of congestion, guiding decongestive therapies, and predicting outcome. Purpose This exploratory biomarker substudy of the SUGAR-DM-HF trial investigated the relationship of CA-125 levels with markers of congestion, and the effect of the SGLT2 inhibitor empagliflozin on serum CA-125 levels. Methods We conducted a multicentre, randomised, double-blind, placebo-controlled trial investigating the effects of empagliflozin in patients with New York Heart Association functional class II-IV, left ventricular ejection fraction (LVEF) ≤40%, and type 2 diabetes or prediabetes.[1] Patients were randomly assigned 1:1 to empagliflozin 10mg daily or placebo. Blood biomarker samples were collected at baseline, weeks 12 and 36. Other measures of congestion assessed included cardiovascular magnetic resonance (CMR), kidney magnetic resonance imaging (MRI), transthoracic echocardiography (TTE), lung ultrasound (LUS), and bioelectrical impedance analysis (BIA). Results Among 105 patients [mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% (9.8%)], median [IQR] CA-125 was 11.2 [8.9-17.6] U/mL. At baseline, those with higher CA-125 had a longer duration of diabetes, higher heart rate, lower LVEF, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP), were more likely to have a pleural effusion and be on a loop diuretic, but serum creatinine was similar. At baseline, CA-125 levels weakly correlated with NT-proBNP, the presence of a pleural effusion, number of B-lines, inferior vena cava (IVC) diameter, tricuspid regurgitation velocity, E/e’ average, apparent extracellular volume (aECV) of the right whole kidney,[2] and total body water (FIGURE 1). CA-125 levels were not significantly different between groups at week 12 or 36 (FIGURE 2). The beneficial effect of empagliflozin on reducing left ventricular end-systolic volume index (LVESVi) was not modified by baseline CA-125 (p interaction = 0.93). Change in CA-125 was not associated with change in the co-primary outcomes (LVESVi and left ventricular global longitudinal strain) at week 36, nor with change in NT-proBNP or change in body weight at week 12 or 36. Conclusion Among patients with HFrEF, CA-125 levels were not strongly associated with markers of congestion assessed with CMR, kidney MRI, TTE, LUS and BIA. CA-125 levels were not different between groups at week 12 or 36, although this trial was not powered for this outcome.Correlation heatmap (Spearman’s rho).Change in CA-125 levels.

Dynamic monitoring of serum CEA and CA19-9 predicts the prognosis of postoperative stage II colon cancer

BackgroundWe sought to investigate the prognostic significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) dynamics for stage II colon cancer patients undergoing radical resection. MethodsThis study retrospectively analyzed 1517 stage II colon cancer patients admitted to the Harbin Medical University Cancer Hospital from January 2011 to December 2016. To observe the relationship between tumor markers dynamic monitoring and survival, we calculated cut-off values for ΔCEA and ΔCA19-9. Group according to the cut-off values and compare the differences in survival between subgroups. ResultsPreoperative CA199 (HR = 3.122), postoperative CEA (HR = 2.941) and histological type (HR = 2.855) were independent prognostic factors in multivariate Cox proportional hazards models. The 5-year overall survival (OS) in the patients with normal preoperative CEA and CA19-9 was significantly better than the patients with elevated preoperative CEA or CA19-9 and the patients with elevated preoperative CEA and CA19-9 (92.6 % vs. 87.6 % vs. 81.0 %, P < 0.05). 469 patients with normal pre- and post-operative CEA had the highest 5-year OS (93.5 %, P < 0.05). Among the 177 patients with elevated pre- and post-operative CEA, the 5-year OS rate was only 81.8 % (P < 0.05). The cut-off values for Δ CEA and Δ CA19-9 in stage II colon cancer patients with elevated preoperative tumor markers were 2.625 ng/ml and 7.835 U/ml, respectively. The Kaplan-Meier curves showed that Δ CEA≥2.625 ng/ml and Δ CA19-9≥7.835 U/mL were associated with better outcome (87.8 % vs. 79.6 %, P < 0.05; 85.8 % vs. 79.1 %, P > 0.05). At the same time, we found that adjuvant chemotherapy significantly improved 5-year OS in patients with elevated preoperative CEA or CA19-9 (91.0 % vs. 80.9 % and 89.6 % vs. 80.2 %, P < 0.05). ConclusionsPersistent postoperative elevation of CEA/CA19-9 is associated with a poor prognosis. CEA and CA19–9 may be high-risk factors for postoperative adjuvant therapy in stage II colon cancer patients. For stage II colon cancer patients with elevated preoperative CEA, patients with Δ CEA<2.625 ng/ml have poor survival and can improve prognosis by receiving adjuvant therapy.

FTO, PIK3CB serve as potential markers to complement CEA and CA15-3 for the diagnosis of breast cancer.

The diagnostic efficacy of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) is limited in breast cancer (BC), highlighting the necessity of exploring novel biomarkers to improve for BC diagnosis. Therefore, we assessed the diagnostic value of fat mass and obesity-associated protein (FTO), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit β (PIK3CB) as a potential complementary biomarker to CEA and CA153 in breast cancer by measuring serum FTO,PIK3CB levels. FTO, PIK3CB, CEA and CA15-3 levels were measured in 112 BC patients and 64 healthy controls using enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Spearman's rank correlation analysis was conducted to assess the correlation between the levels of the 2 markers. The relationships between FTO, PIK3CB, CEA, CA15-3 and clinical characteristics were evaluated. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic value of FTO, PIK3CB, CEA and CA15-3 of BC. Serum FTO, PIK3CB, CEA and CA15-3 levels were significantly increased in BC. There was no correlation between FTO, PIK3CB and CEA, CA15-3. FTO and PIK3CB demonstrated significant diagnostic performance for breast cancer, with FTO achieving a specificity of 90.63%. The diagnostic performance of 2-four biomarker combinations was significantly superior to individual CEA or CA153, with a combined panel of 4 biomarkers yielding an area under the curve (AUC) of 0.918, sensitivity of 81.25% and specificity of 85.94%. In early-stage breast cancer (I + II), the combination of FTO, PIK3CB, CEA and CA153 yielded an AUC of 0.895, sensitivity of 77.22% and specificity of 85.71%. FTO and PIK3CB can be served as potential biomarkers to complement CEA and CA15-3 for BC diagnosis. Combining FTO, PIK3CB, CEA and CA15-3 improves the diagnostic efficiency of breast cancer.

High expression of RAB7A is associated with poor prognosis of gastric cancer by promoting tumor invasion

To explore the expression level of Ras-related protein 7A (RAB7A) in gastric cancer and its prognostic implications. Based on data from public databases and a cohort of 104 patients undergoing radical gastrectomy for gastric cancer in our hospital, we analyzed RAB7A expression level in gastric cancer and adjacent tissues and its association with clinicopathological parameters and prognosis of the patients. Bioinformatic analysis was performed to predict the pathways of RAB7A to affect gastric cancer invasion. In gastric cancer MGC803 cells with lentivirus-mediated interference or overexpression of RAB7A, the changes in extracellular matrix (ECM) degradation and cell migration and invasion were analyzed using immunoblotting, wound healing assay and Transwell experiments. The data from public cancer databases and clinical samples showed a significantly higher expression of RAB7A in gastric cancer tissues than in normal or adjacent tissues (P<0.01) with a close correlation with a poorer patient survival (P<0.01) and a positive correlation with serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P<0.001). Univariate and multivariate Cox regression analyses suggested that a high RAB7A expression was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR: 2.882; 95% CI: 1.459-5.693). ROC curve analysis showed that at the cut-off value of 2.625, RAB7A expression level had a sensitivity of 84.62% and a specificity of 71.15% for predicting postoperative 5-year mortality of the patients. Bioinformatic analysis suggested that RAB7A was involved in ECM degradation and activation of PI3K/AKT signaling in gastric cancer. MGC803 cells with RAB7A overexpression showed activation of the PI3K/AKT signaling pathway (P<0.01) with enhanced expressions of MMP-2 and MMP-9 (P<0.01) and cell migration and invasion capacities (P<0.01). RAB7A is highly expressed in gastric cancer tissues and affects the patients' prognosis possibly by activating the PI3K/AKT signaling pathway and enhancing ECM degradation to promote tumor invasion.

Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with colorectal carcinoma.

To investigate the expression levels and diagnostic value of glial cell line-derived neurotrophic factor (GDNF), carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) in patients with colorectal carcinoma (CRC). 50 CRC patients at our hospital from Feb. 2020 to Feb. 2021 were chosen as the malignant group, another 50 patients with benign colonic diseases were chosen as the benign group, and 50 healthy people who came to our hospital for physical examination during the same period were considered as the control group. Fasting peripheral venous blood was taken from all research subjects in the morning and tested by a fully-automated electrochemiluminometer to determine the GDNF, CEA and CA199 levels. The sensitivity and specificity of the combined detection of the three indexes for CRC were analyzed, and the receiver operating characteristic (ROC) curve was plotted to record the area under the curve (AUC). The malignant group had remarkably higher CEA and CA199 levels (P<0.001) and a lower GDNF level (P<0.001) when compared with the benign and control groups. The sensitivity, specificity, positive predictive value and negative predictive value of the combined detection were 96.0%, 94.0%, 88.9% and 97.9%, respectively. Under combined detection, AUC (95% CI) = 0.950 (0.909-0.991), standard error = 0.021, and P<0.001. The combined diagnosis of serum GDNF, CEA and CA199 is a reliable method to improve the diagnostic accuracy of CRC, and this strategy can effectively reduce the missed diagnosis rate and has high application value in clinic.

The clinical significance and diagnostic value of serum Dickkopf1 and CKAP4 levels in patients with gastric cancer: a prospective study.

Gastric cancer is diagnosed at an advanced stage in most patients, and the prognosis is poor. Novel biochemical markers of high diagnostic value for the detection of the disease are therefore important. Dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) have been extensively studied as biomarkers in cancer patients. Serum DKK1 and CKAP4 levels in 58 patients with gastric cancer and 41 healthy controls were examined using an ELISA kit in this prospective study. The patients were subdivided into groups based on pathological TNM staging and histological grades. Serum levels of both proteins in the patients with gastric cancer were measured preoperatively, 10 and 30 days after surgery. Serum DKK1 and CKAP4 levels were significantly higher in the gastric cancer group compared to the healthy controls (p<0.05). Serum levels of both proteins increased in line with the pathological stage and histological grade of the gastric cancer. Serum CKAP4 and DKK1 levels decreased after surgical resection. Both serum levels also decreased significantly on day 30 after surgery compared to day 10 (p<0.05). Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) positivity rates were below 20% in the gastric cancer group, while the diagnostic value (sensitivity and specificity) of serum CKAP-4 and DKK1 exceeded 80%. DKK1 and CKAP4 are biomarkers of high diagnostic value that can be used to diagnose and predict the severity of gastric cancer. These proteins can also be employed for disease monitoring after surgical resection. The diagnostic value of these proteins is higher than that of biomarkers such as CEA and CA19-9, which are routinely used in clinical practice.

Beta2-Microglobulin as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram.

Accurate prognosis is crucial for improving hepatocellular carcinoma (HCC) patients, clinical management, and outcomes post-liver resection. However, the lack of reliable prognostic indicators poses a significant challenge. This study aimed to develop a user-friendly nomogram to predict HCC patients' post-resection prognosis. We retrospectively analyzed the data from 1091 HCC patients, randomly split into training (n=767) and validation (n=324) cohorts. Receiver operating characteristic (ROC) curves determined the optimal cut-off value for alpha1-microglobulin (α1MG) and Beta2-microglobulin (β2MG). Kaplan-Meier analysis assessed microglobulin's impact on survival, followed by Cox regression to identify prognostic factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), calibration curves, area under the ROC curve (AUC), and decision curve analysis (DCA), and were compared with the BCLC staging system, Edmondson grade, or BCLC stage plus Edmondson grade. Patients with high β2MG (≥2.395mg/L) had worse overall survival (OS). The nomogram integrated β2MG, BCLC stage, Edmondson grade, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA199) levels. C-index for training and validation cohorts (0.712 and 0.709) outperformed the BCLC stage (0.660 and 0.657), Edmondson grade (0.579 and 0.564), and the combination of BCLC stage with Edmondson grade (0.681 and 0.668), improving prognosis prediction. Calibration curves demonstrated good agreement between predicted and observed survival. AUC values exceeded 0.700 over time, highlighting the nomogram's discriminative ability. DCA revealed superior overall net income compared to other systems, emphasizing its clinical utility. Our β2MG-based nomogram accurately predicts HCC patients' post-resection prognosis, aiding intervention and follow-up planning. Significantly, our nomogram surpasses existing prognostic indicators, including BCLC stage, Edmondson grade, and the combination of BCLC stage with Edmondson grade, by demonstrating superior predictive performance.