CA72-4 derived from synovial cells inhibits monosodium urate-induced macrophage M1 polarization by activating the TIGIT/SHP-1 axis through binding to Siglec-15

Objective To investigate the clinical significance of combined detection of serum carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA) in the early diagnosis of colorectal cancer. Methods The clinical data of 76 patients with colorectal cancer were collected. The levels of CEA and CA199 in serum of 76 patients with colorectal cancer were examined by chemiluminescence method; the diagnostic sensitivity, specificity and detection rates in the diagosis of colorectal cancer were compared between the CEA or CA199 alone method and the double indexes combination detection method; detection levels of CEA and CA199 in patients in different phases of colorectal cancer were compared; detection levels of CEA and CA199 in patients with intraepithelial neoplasia, carcinoma in situ and invasive carcinoma were compared. Results Compared with CEA and CA199 alone method, the sensitivity and detection rate of CEA and CA199 combination method were significantly higher (P 0.05). The detection rate of CEA alone method was significantly higher than that of CA199 alone method, and the difference was significant (P 0.05). However, there was a significant difference in CA199 level between patients with stage Ⅰ, Ⅱ, Ⅲ and Ⅳ colorectal cancer (P>0.05). The level of CA199 has linear correlation with the stage of cancer. There was no significant difference in CEA levels among patients with intraepithelial neoplasia, carcinoma in situ or invasive carcinoma (P>0.05), but there were significant differences in CA199 levels among patients with intraepithelial neoplasia, carcinoma in situ or invasion of cancer, and level of CA199 in patients with intraepithelial neoplasia was in the normal range. Conclusions Combined detection of tumor markers CEA and CA199 has higher detection rate and better sensitivity than single detection method, level of CA199 marker is related to tumor progression in a certain degree, CEA can even make response in the stage of tumor atypical hyperplasia, so the combination of the two markers of colorectal cancer has significance in early monitoring and early diagnosis of colorectal cancer, which is worthy of clinical promotion and reference. Key words: Carbohydrate antigen 199; Carcinoembryonic antigen; Combined detection; Colorectal cancer; Diagnosis

The present study investigated the associations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels with clinicopathological variables and survival outcomes in Libyan patients with pancreatic ductal adenocarcinoma (PDAC). The clinicopathological variables of 123 patients with PDAC registered at the National Cancer Institute in Misurata, Libya, between 2010 and 2018 were retrospectively analyzed. Blood samples from these patients were analyzed for serum CEA and CA19-9 levels before treatment by electrochemiluminescence immunoassay (double antibody sandwich ELISA) on a Roche cobas e 602 modules. The relationships between CA19-9 and CEA serum levels with clinicopathologic variables and survival outcomes were analyzed using the Kaplan-Meier method, log-rank test and Cox regression analyzes. Cut-off values for serum CEA and CA19-9 levels were 5 ng/ml and 400 U/ml, respectively. The median serum levels of all patients with PDAC for CEA and CA19-9 were 8 ng/ml (1.1-377 ng/ml) and 389 U/ml (1-10,050 U/ml), respectively. Tumors with higher serum CEA and CA19-9 levels were found in 63 and 48% of patients, respectively. Higher CEA and CA19-9 serum levels were significantly associated with more indicators of a malignant phenotype, including a surgically unresectable tumor, unevaluable lymph nodes, advanced stages and distant metastases. Regarding survival, patients with higher serum levels of the biomarkers CEA and CA19-9 had shorter overall survival rates (P<0.016 and (P<0.014, log-rank, respectively) and lower disease-free survival rates (P<0.002 and P<0.0001, log-rank, respectively). The present study demonstrated significant clinical and prognostic value of serum levels of biomarkers CEA and CA19-9 for Libyan patients with PDAC. Moreover, patients with PDAC with higher serum CEA and CA19-9 levels had more aggressive tumors, higher rates of disease recurrence and shorter overall survival rates and thus required more vigilant follow-up. Further multinational studies with larger PDAC cohorts are warranted to confirm these findings in terms of improved clinical decision making, more effective management and improved survival.

Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer

Gastric cancer (GC) is a common malignant tumor of the digestive system with a high degree of malignancy. It usually develops insidiously without any specific symptoms in the early stages. As one of the diseases caused by abnormal gene changes, GC has abnormal expression of various oncogenes and products during its development. Tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and carbohydrate antigen 724 (CA724) are not expressed or lowly expressed in normal people, but significantly increased after carcinogenesis. Monitoring the changes in the levels of tumor markers such as CEA, CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors. To investigate the expression of CEA, CA199 and CA724 in GC and their correlation with clinical features, hoping to provide more effective markers for the early preventive diagnosis of GC. Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group, and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group. The serum CEA, CA199, and CA724 levels were compared between the two groups, and the serum CEA, CA199, and CA724 levels were compared in patients with GC at different TNM stages, and the differences in the positive rates of CEA, CA199, and CA724 alone and in combination in detecting TNM stages of GC and GC were compared. In addition, the relationship between the levels of tumor markers CEA, CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed. The relationship between the serum levels of CEA, CA199 and CA724 and the survival period of GC patients was analyzed by Pearson. The serum levels of CEA, CA199 and CA724 in GC group were significantly higher than those in control group (P < 0.05). With the increase of TNM stage, the serum CEA, CA199 and CA724 expression levels in GC patients increased significantly, and the differences between groups were statistically significant (P < 0.05). The positive rate of the CA724 single test was higher than that of CEA and CA199 single test (P < 0.05). The positive rate of the three combined tests was 95.40% (83/87), which was higher than that of CEA, CA199 and CA724 single tests. The difference was statistically significant (P < 0.05). The combined detection positive rates of CEA, CA199, and CA724 in stages I, II, III, and IV of GC were 89.66%, 93.10%, 98.85%, and 100.00% respectively, all of which were higher than the individual detection rates of CEA, CA199, and CA724. The differences were statistically significant (P < 0.05). There was no significant difference in serum CEA, CA199 and CA724 levels between GC patients with different genders, smoking history and alcohol history (P > 0.05). However, the serum CEA, CA199 and CA724 levels were significantly higher in GC patients aged ≥ 45 years, TNM stage III-IV, with lymph node metastasis and tumor diameter ≥ 5 cm than in GC patients aged < 45 years, TNM stage I-II, without lymph node metastasis and tumor diameter < 5 cm (P < 0.05). The expression levels of serum tumor markers CEA, CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage. The levels of CEA, CA199 and CA724 are related to age, TNM stage, lymph node metastasis and tumor diameter. The combined detection of CEA, CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.

AimThe present study aimed to examine the capability of p- signal transducer and activator of transcription (STAT)3 and interleukin-17 (IL-17), along with two known tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), for disease prognosis. Moreover, the associations among biomarkers and clinicopathological parameters were evaluated to uncover the potential mechanisms responsible for their correlations with lung adenocarcinoma (LAD) prognosis. MethodsFive LAD-related parameters were used in the study: CEA, CA125, STAT3, p-STAT3, and IL-17. Spearman and chi-square correlation tests were used to explore the relationships between some clinicopathological variables and parameter expression levels and the associations among these five parameters. ResultsThe disease-specific survival decreased with the positive expression of CEA, CA125, p-STAT3, and IL-17, with no significant difference in the expression level of STAT3. Combinations of p-STAT3 and IL-17, CEA and p-STAT3, CEA and IL-17, CA125 and p-STAT3, and CA125 and IL-17 had higher predictive values in LAD prognosis. The correlation analyses indicated the synergic activities of STAT3, p-STAT3, and IL-17 and the coordinated expression of CEA, CA125, p-STAT3, and IL-17. The tumor-node-metastasis (TNM) stage significantly correlated with the levels of CA125 and p-STAT3. ConclusionsElevated levels of CEA, CA125, p-STAT3, and IL-17 alone and/or combinations of p-STAT3 and IL-17, CEA and p-STAT3, CEA and IL-17, CA125 and p-STAT3, and CA125 and IL-17 were recommended as the prognostic predictors of unfavorable clinical outcomes in patients with postoperative LAD. Also, p-STAT3 and IL-17 combined with CA125 and CEA helped in predicting the overall survival of patients with LAD and informing the TNM stage.

Objective To explore the mechanism of ubiquitin specific peptidase 21 (USP21) increasing the stability of forkhead box protein M1 (FOXM1) and promoting M2 polarization of macrophages in endometriosis (EM). Methods Eutopic endometrial stromal cells (EESC) collected from patients and normal endometrial stromal cells (NESC) from routine health examiners were cultured in vitro, and the expression levels of USP21 and FOXM1 were detected using RT-qPCR and Western blot. EESCs were co-cultured with macrophages. M1 polarization markers of interleukin 6 (IL-6) and CXC chemokine ligand 10 (CXCL10) and M2 polarization markers of CD206 and fibronectin 1 (FN1) were tested using RT-qPCR. M2 marker CD206 was further detected by flow cytometry. IL-6, tumor necrosis factor-alpha (TNF-α), IL-10, and transforming growth factor-beta (TGF-β) levels in cell supernatant were detected by ELISA. Co-immunoprecipitation was used to assess the interaction between USP21 and FOXM1, and the ubiquitination level of FOXM1. FOXM1 protein stability was detected through cycloheximide (CHX) assay. Results USP21 and FOXM1 expression levels in the EESC group were significantly increased compared with those in the NESC group; compared with the NESC + M0 group, the EESC + M0 group showed no significant difference in the expression of M1 polarization markers (IL-6 and CXCL10), but increased expression of M2 polarization markers (CD206 and FN1), along with notably increased number of M2 macrophages; there was no significant difference in IL-6 and TNF-α levels, but increased levels of IL-10 and TGF-β in the cell supernatant. The above findings indicated that the deubiquitinase USP21 was highly expressed in EM, promoting M2 polarization of macrophages. Knocking down USP21 or FOXM1 can inhibit M2 polarization of EM macrophages. USP21 interacted with FOXM1 in EESC, leading to a decrease in FOXM1 ubiquitination level and an increase in FOXM1 protein stability. Overexpression of FOXM1 reversed the inhibitory effect of knocking down USP21 on M2 polarization of EM macrophages. Conclusion The deubiquitinase USP21 interacts with FOXM1 to increase the stability of FOXM1 and promote M2 polarization of EM macrophages.

Carbohydrate Antigen 125 (CA125) has emerged as a potential biomarker in patients with heart failure (HF). This meta-analysis comprehensively evaluates the association between CA125 levels and clinical outcomes across HF populations. We conducted this study based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). We systematically searched PubMed, Scopus, Web of Science, and Embase libraries up to April 2025. We selected the original English-language investigations that reported the association between CA125 levels and clinical outcomes in cases with HF. The random-effects model and Hartung-Knapp-Sidik-Jonkman method were used to pool effect sizes and report summary statistics. The current review was registered in PROSPERO (CRD420251023141). A total of 20,458 cases were included from 29 studies, with an average age of 70.3 years, and 36.1% of cases were women. The average cut-off level was 37.78 U/mL, and 35 U/mL was mainly used as the CA125 cut-off level. A meta-analysis of nine studies that reported the risk of experiencing endpoint events (death or HF-related hospitalization) showed significantly higher risk (HR 2.23, 95% CI 1.69-2.93; p < 0.01; I2 = 75.0%) among the patients with higher CA125 levels compared to those with lower levels. The increased risk remained significant across the acute heart failure (AHF) (HR based on two studies: 1.88, 95% CI 1.54-2.30; p < 0.01; I2 = 39.6%) and chronic heart failure (CHF) (HR based on seven studies: 2.52, 95% CI 1.69-3.77; p < 0.01; I2 = 77.4%) subgroups. Furthermore, a correlation meta-analysis of 13 studies revealed a significant direct correlation between CA125 and pro-BNP levels (r = 0.42; 95% CI 0.30 to 0.54; p < 0.01; I2 = 96.9%). The current review findings revealed CA125 as a significant prognostic factor of mortality and hospitalization risks in HF population. Furthermore, CA125 could be a non-invasive and operator-independent tool for evaluating disease severity and monitoring response to therapy. We suggested CA125 for monitoring various treatments in individuals with HF, specifically diuretic therapy. Further prospective studies are needed to determine the optimal cut-off for CA125 levels in HF.

PurposeCarcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are tumor-associated antigens. An increased serum level of CEA and CA19-9 separately has been reported in diabetes. In this study, we examined the composite effect of elevated serum levels of both CEA and CA19-9 on subjects with type 2 diabetes and prediabetes.Patients and MethodsA total of 3568 adults who attended a health examination were enrolled into this cross-sectional study. Subjects were grouped into four groups according to the median serum CEA and CA19-9 levels.ResultsSubjects with high CEA and high CA19-9 levels had the highest proportions of diabetes (43.9%) and prediabetes (33.04%). There was a statistically significant trend in the proportion of diabetes across the four groups (P < 0.001). Multivariable logistic regression analysis revealed higher risks of type 2 diabetes in subjects with high CEA and low CA19-9 levels (odds ratio [OR] = 2.10, 95% confidence interval [CI]: 1.39–3.18, P < 0.001) and in those with high CA19-9 and low CEA levels (OR = 2.18, 95% CI: 1.42–3.34, P < 0.001) than in those with low CEA and low CA19-9 levels; among these four groups, the highest risk of type 2 diabetes was observed in subjects with high CEA and high CA19-9 levels (OR = 2.65, 95% CI: 1.81–3.88, P < 0.001). The risk of prediabetes was significantly higher only in subjects with high CEA and high CA19-9 levels compared to those with low CEA and low CA19-9 levels (OR = 1.32, 95% CI: 1.08–1.61, P = 0.006).ConclusionCEA and CA19-9 had a synergistic ability to increase the risk of type 2 diabetes and prediabetes.

Increased expression of cell adhesion molecule CD44v6, integrin-β1, carbohydrate antigen 199 (CA199), and carcinoembryonic antigen (CEA) are closely associated with the progression and metastasis of numerous cancers. In this study, peripheral blood mononuclear cell (PBMC) and serum samples were collected from 37 pancreatic cancer patients and 12 healthy people. A novel triplex TaqMan real-time reverse transcription polymerase chain reaction assay was used to measure the expression levels of CD44v6 and integrin-β1 gene in PBMCs, while chemiluminescence and enzyme-linked immunosorbent assay were used to measure the levels of CA199 and CEA expression in serum. The results showed that both the levels of CD44v6 and integrin-β1 expression had significant correlation with clinical stage, lymph node, and liver metastasis of pancreatic cancer (P < 0.05). Age, tumor size, tumor differentiation, clinical stage, lymph nodes, and liver metastasis were significantly associated with the levels of CA199 and CEA expression (P < 0.05). The levels of CD44v6, integrin-β1, CA199, and CEA expression in the patients prior cryosurgery and chemotherapy were significantly higher than those in the control group (P < 0.05), whereas no significant difference was found between the patients 1 month post cryosurgery and control group (P > 0.05). The expression levels of CD44v6, integrin-β1, CA199, and CEA in the patients 1 month post cryosurgery were significantly lower than those in the patients prior cryosurgery (P < 0.05). Interestingly, no significant difference was found for the CD44v6, integrin-β1, CA199, and CEA levels between the patients prior and post-chemotherapy (P > 0.05). The higher expression of CD44v6, integrin-β1, CA199, and CEA are closely related to the progression and metastasis of pancreatic cancer and may play a important role in the curative evaluation of cryosurgery of pancreatic cancer.

BackgroundTranscatheter aortic valve implantation (TAVI) is a minimally invasive, emerging therapy in surgically high risk, or inoperable patients. Parameters used for risk classification have some deficiencies in the selection of patients. The objective of this study is to evaluate the impact of TAVI on carbohydrate antigen 125 (CA125) and N-Terminal pro Brain-type Natriuretic Peptide (NT-proBNP) as biomarkers that have been used frequently in recent years, and also the relationship of these biomarkers to prognosis.Methods & ResultsTranscatheter aortic valve implantation was practiced on 31 patients in this study. Then, CA125 and NT-proBNP levels studied in patients prior to and after the TAVI were evaluated. The patients were also grouped in accordance with their left ventricular ejection fraction (LVEF) and CA125 levels (LVEF ≥ 40% and < 40%; CA125 ≤ 35 U/L and > 35 U/L). The TAVI operation was successfully performed in all patients. There was no in-hospital mortality and substantial improvement in functional capacity was detected at follow ups. In addition, a statistically significant decrease was detected in post-TAVI CA125 and NT-proBNP levels of all patients (CA125 83.8 ± 18.1 U/L vs. 64.3 ± 14.2 U/L, P = 0.008; NT-proBNP: 4633.6 ± 627.6 pg/mL vs. 2866.3 ± 536.8 pg/mL, P < 0.001). In groups divided according to the CA125 levels, there was also statistically significant post-TAVI decline in CA125 levels. Within CA125 > 35 U/L and LVEF < 40% groups, the permanent need for a pacemaker was required in one (3.2%) patient and mortality was observed in two (6.4%) patients after TAVI at follow up.ConclusionsThe results show that TAVI can be performed effectively and reliably in patients with high baseline levels of CA125 and NT-proBNP. These biomarkers are reduced substantially with TAVI, while high biomarker levels are associated with undesired events, and certainly, these biomarkers can be used for risk classifications in patient selection for TAVI.

BackgroundElevated plasma carbohydrate antigen-125 (CA-125) levels are strongly associated with new-onset atrial fibrillation (AF) and heart failure, but the relationship between plasma CA-125 level and AF recurrence following radiofrequency catheter ablation (RFCA) remains poorly investigated. We aimed to assess whether elevated CA-125 levels are related to long-term AF recurrence following RFCA.MethodsPreoperative CA-125 levels were determined in AF patients undergoing initial RFCA. Multivariate-adjusted Cox models were constructed to determine the relationship between CA-125 levels and AF recurrence. Multivariate logistic regression analyses were performed to determine predictors of AF recurrence.ResultsOf the 353 enrolled patients, 85 patients (24.1%) had AF recurrence at the 12-month follow-up. These patients had significantly higher baseline CA-125 levels than those without AF recurrence [(18.71 ± 12.63) vs. (11.27 ± 5.40) U/mL, P < 0.001]. The incidence of AF recurrence across quartiles 1–4 of CA-125 was 11.5%, 13.3%, 21.6% and 50.0%, respectively (P-trend < 0.001). The adjusted hazard ratios (aHRs) for AF recurrence across quartiles 1–4 of CA-125 were 1.00 (reference), 1.085 (95% CI, 0.468–2.520), 1.866 (95% CI, 0.867–4.019), and 4.246 (95% CI, 2.113–8.533), respectively (P-trend < 0.001). A similar effect was obtained when CA-125 was studied as continuous data (aHR per unit increase in LnCA-125, 3.225, 95% CI, 2.258–4.606; P < 0.001). When a predefined CA-125 cut-off of 13.75 U/mL was established, patients with CA-125 ≥ 13.75 U/mL had a higher risk of recurrent AF than those with CA-125 < 13.75 U/mL (aHR, 3.540, 95% CI, 2.268–5.525, P < 0.001). Multivariate analysis revealed CA-125, high-sensitivity C-reactive protein, and left atrium anteroposterior diameter as independent risk factors for AF recurrence.ConclusionsElevated preoperative CA-125 levels are related to a higher risk of AF recurrence and can independently predict AF recurrence following RFCA.

Ovarian cancer is one of the common female malignant tumors. The early diagnosis and treatment of ovarian cancer has been a research hotspot. Therefore, we aimed to investigate the correlations between the levels of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), D-dimer (DDI), and fibrinogen degradation product (FDP) in patients with type II epithelial ovarian cancer.From January 2018 to January 2019, a total of 952 patients who underwent initial surgery for epithelial ovarian cancer were enrolled in this study. Peripheral venous blood was taken before operation, and the levels of CA125, HE4, DDI, and FDP were tested. The correlations between the levels of CA125, HE4, DDI, and FDP and other clinical indicators (such as presence or absence of chemotherapy, surgical conditions) were analyzed.The level of DDI or FDP was statistically associated with age, chemotherapy, Figo staging, surgical procedure, HE4 level, and CA125 level, respectively. Moreover, the Figo staging was statistically correlated with the levels of HE4 and CA125. Besides, we found the levels of CA125 and HE4 were positively correlated with the levels of DDI and FDP.The levels of CA125 and HE4 are the traditional detection indexes for patients with type II epithelial ovarian cancer, and these 2 indicators reflected the degree of disease and prognosis. The levels of DDI and FDP were closely related to the levels of CA125 and HE4 in type II epithelial ovarian cancer, and they also helped to assess the prognosis of epithelial ovarian cancer. Further larger-scale prospective cohort studies are warranted to determine these associations in the future.

Objective: To investigate the clinical value of neutrophil-lymphocyte ratio (NLR), fibrinogen (FIB), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis and prognosis of colorectal cancer. Methods: A case-control study design was used to select 155 patients with colorectal cancer[98 males and 57 females, aged (63.12±13.99)years old], 90 patients with colorectal polyps[62 males and 28 females, aged (56.86±12.74)years old] and 150 healthy subjects[93 males and 57 females, aged (57.02±10.91)years old] from the First Affiliated Hospital of Nanjing Medical University from October 2017 to March 2018. Blood routine tests were detected by instrument method, FIB was detected by Clauss method, and CEA and CA19-9 were detected by electrochemiluminescence method. The levels of the NLR, FIB, CEA and CA19-9 in the 3 groups were compared. The diagnostic efficacy of NLR, FIB, CEA and CA19-9 of colorectal cancer was compared according to the ROC curve. The relationship between the level of NLR, FIB, CEA and CA19-9 and their clinicopathological features in colorectal cancer patients was assessed. According to the median levels of NLR, FIB, CEA and CA19-9, 112 follow-up of colorectal cancer patients could be divided into the high-value group and the low-value group. Kaplan-Meier, log-rank test and Cox regression analysis were used to analyze the relationship between the levels of the four indicators and the prognosis of colorectal cancer. Results: The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were 2.11(1.52, 2.86), 3.21(2.58, 3.86)g/L, 3.93(2.27, 8.78)μg/L, 15.11(9.10, 25.73)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were 1.74(1.39, 2.17), 2.54(2.26, 3.03)g/L, 1.99(1.18, 2.70)μg/L, 9.83(6.13, 15.68)U/ml. The levels of NLR, FIB, CEA and CA19-9 in healthy control group were 1.68(1.33, 2.28), 2.56(2.30, 2.82)g/L, 1.85(1.28, 2.59)μg/L, 10.03(6.86, 13.26)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were significantly higher than those in colorectal polyp group (Z values were 3.568, 5.913, 6.880 and 4.022,P values were all<0.05) and healthy control group(Z values were 3.916, 7.381, 9.131 and 5.251,P values were all<0.05). The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were not remarkably different from those in healthy control group (Z values were 0.217, 0.179, 0.320 and 0.061,P values were all>0.05). The diagnostic performance of CEA was the best in single test, followed by FIB, CA19-9 and NLR. The sensitivity of combined NLR+FIB+CEA or NLR+FIB+CEA+CA19-9 was the highest with 72.3%. NLR and FIB levels were associated with tumor sites (Z values were 3.587 and 7.089,P values were both<0.05). FIB and CEA levels were correlated with the depth of tumor invasion (Z values were 3.250 and 3.245, P values were both <0.05). NLR, FIB, CEA and CA19-9 levels were both associated with lymph node metastasis (Z values were 2.010, 3.276, 3.312 and 2.921, P values were all<0.05). The prognosis of patients in the high-value NLR, FIB, CEA and CA19-9 groups was significantly worse than that in the low-value group (χ2 values were 5.744, 6.048, 4.389 and 6.942,P values were all<0.05).Cox multivariate regression analysis showed lymph node metastasis, NLR >2.15 and CA19-9 >15.47 U/ml are independent factors affecting the prognosis of colorectal cancer. Conclusion: NLR, FIB, CEA and CA19-9 can be applied in the auxiliary diagnosis and prognosis of colorectal cancer.

Inflammation But Not Biliary Obstruction Is Associated With Carbohydrate Antigen 19-9 Levels in Patients With Primary Sclerosing Cholangitis

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.