Carbohydrate Antigen Research Articles

Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer

PurposeThis study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). MethodsA cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. ResultsThe study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. ConclusionThe study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.

Novel tumor marker index using carcinoembryonic antigen and carbohydrate antigen 19-9 is a significant prognostic factor for resectable colorectal cancer

We evaluated the usefulness of a newly devised tumor marker index (TMI), namely, the geometric mean of normalized carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), in determining colorectal cancer (CRC) prognosis. This retrospective cohort study included 306 patients with stages I–III CRC who underwent elective laparoscopic resection between April 2010 and March 2020. Survival rates and risk factors of relapse-free survival (RFS) and cancer-specific survival (CSS) were analyzed using Kaplan–Meier curves and Cox proportional hazards model. High-TMI group (122 patients) had significantly lower rates (95% confidence interval [95% CI]) for 5-year RFS (89.7%, 83.9–93.5 vs. 65.8%, 56.3–73.8, p < 0.001) and CSS (94.9%, 89.4–97.6 vs. 77.3%, 67.7–84.4, p < 0.001) than low-TMI group. Multivariate analysis (hazard ratio [95% CI]) indicated ≥ T3 disease (RFS: 2.69, 1.12–6.45, p = 0.026; CSS: 7.64, 1.02–57.3, p = 0.048), stage III CRC (RFS: 3.30, 1.74–6.28, p < 0.001; CSS: 6.23, 2.04–19.0, p = 0.001), and high TMI (RFS: 2.50, 1.43–4.38, p = 0.001; CSS: 3.80, 1.63–8.87, p = 0.002) as significant RFS and CSS predictors. Area under the curve (AUC) of 5-year cancer deaths (0.739, p < 0.001) was significantly higher for TMI than for CEA or CA19-9 alone. Preoperative TMI is a useful prognostic indicator for patients with resectable CRC.

Serum Carbohydrate Antigen 19-9 and Metabolite Hypotaurine Are Predictive Markers for Early Recurrence of Pancreatic Ductal Adenocarcinoma.

A significant number of patients experience early recurrence after surgical resection for pancreatic ductal adenocarcinoma (PDAC), negating the benefit of surgery. The present study conducted clinicopathologic and metabolomic analyses to explore the factors associated with the early recurrence of PDAC. Patients who underwent pancreatectomy for PDAC at Kagawa University Hospital between 2011 and 2020 were enrolled. Tissue samples of PDAC and nonneoplastic pancreas were collected and frozen immediately after resection. Charged metabolites were quantified by capillary electrophoresis-mass spectrometry. Patients who relapsed within 1 year were defined as the early recurrence group. Frozen tumor tissue and nonneoplastic pancreas were collected from 79 patients. The clinicopathologic analysis identified 11 predictive factors, including preoperative carbohydrate antigen 19-9 levels. The metabolomic analysis revealed that only hypotaurine was a significant risk factor for early recurrence. A multivariate analysis, including clinical and metabolic factors, showed that carbohydrate antigen 19-9 and hypotaurine were independent risk factors for early recurrence ( P = 0.045 and P = 0.049, respectively). The recurrence-free survival rate 1 year after surgery with both risk factors was only 25%. Our results suggested that tumor hypotaurine is a potential metabolite associated with early recurrence. Carbohydrate antigen 19-9 and hypotaurine showed a vital utility for predicting early recurrence.

CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin

Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting β-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea.

Intrahepatic duct (IHD) stones are among the most important risk factors for cholangiocarcinoma (CCC). Approximately 10% of patients with IHD stones develop CCC; however, there are limited studies regarding the effect of IHD stone removal on CCC development. To investigate the association between IHD stone removal and CCC development. We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020. CCC occurred in 36 of the 397 enrolled patients. In univariate analysis, chronic hepatitis B infection (11.1% vs 3.0%, P = 0.03), carbohydrate antigen 19-9 (CA19-9, 176.00 vs 11.96 II/mL, P = 0.010), stone located in left or both lobes (86.1% vs 70.1%, P = 0.042), focal atrophy (52.8% vs 26.9%, P = 0.001), duct stricture (47.2% vs 24.9%, P = 0.004), and removal status of IHD stone (33.3% vs 63.2%, P < 0.001) were significantly different between IHD stone patients with and without CCC. In the multivariate analysis, CA19-9 > upper normal limit, carcinoembryonic antigen > upper normal limit, stones located in the left or both lobes, focal atrophy, and complete removal of IHD stones without recurrence were independent factors influencing CCC development. However, the type of removal method was not associated with CCC risk. Complete removal of IHD stones without recurrence could reduce CCC risk.

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

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

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial.

The prognostic value of the Systemic Inflammation Response Index (SIRI) in advanced pancreatic cancer is recognized, but its correlation with patients´ nutritional status and outcomes remains unexplored. To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer. The PANTHEIA-Spanish Society of Medical Oncology (SEOM) study is a multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional initiative, promoted by the SEOM Real World-Evidence work group. This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI. The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers. Patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023, were included. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained within 15 days before initiation chemotherapy. This study evaluated associations between overall survival (OS), SIRI and weight loss. A total of 50 patients were included. 66% of these patients were male and the median age was 66 years. Metastasis sites: 36% liver, 12% peritoneal carcinomatosis, 10% lung, and 42% multiple locations. Regarding the first line palliative chemotherapy treatments: 50% received gemcitabine plus nab-paclitaxel; 28%, modified fluorouracil, leucovorin, irinotecan and oxaliplatin, and 16% were administered gemcitabine. 42% had a weight loss > 5% in the three months (mo) preceding diagnosis. 21 patients with a SIRI ≥ 2.3 × 103/L exhibited a trend towards a lower median OS compared to those with a SIRI < 2.3 × 103/L (4 vs 18 mo; P < 0.000). Among 21 patients with > 5% weight loss before diagnosis, the median OS was 6 mo, in contrast to 19 mo for those who did not experience such weight loss (P = 0.003). Patients with a weight loss > 5% showed higher SIRI levels. This difference was statistically significant (P < 0.000). For patients with a SIRI < 2.3 × 103/L, those who did not lose > 5% of their weight had an OS of 20 mo, compared to 11 mo for those who did (P < 0.001). No association was found between carbohydrate antigen 19-9 levels ≥ 1000 U/mL and weight loss. A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss. An elevated SIRI is suggested as a predictor of survival, emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Evaluation of some oncomarkers and cytokines in vinyl chloride workers

Currently, there is a serious problem of the risk of developing oncopathology in chemical enterprises. Numerous workers in the chemical industry, including vinyl chloride and polyvinyl chloride (VC and PVC), are exposed to a complex of chemical compounds that, among other things, have carcinogenic effects and affect many body systems. The immune system has the ability to recognize malignant cells with subsequent activation and hyperactivation of immune responses, including cytokine production. To date, the details of cytokine control and, moreover, the ways of manipulating the antitumor immune response remain insufficiently studied.&#x0D; The study aims to evaluate changes in serum concentrations of certain cancer markers, cytokines and their relationships in highly trained vinyl chloride production workers.&#x0D; The authors have determined serum concentrations of cancer markers (CA 19-9; CEA) and interleukins (IL-1β, IL-2, IL-4, IL-8, TNF-α, INF-γ) using the method of solid-phase enzyme immunoassay.&#x0D; As a result of the study, the researchers found that the highest concentrations of carbohydrate antigen (CA 19-9) are characteristic of trained workers, and when analyzing their level of embryonic cancer antigen (CEA), its tendency to increase attracts attention, which significantly increases the likelihood of cancer pathology in workers. Also, in most workers of this production, we observed hyperproduction of IL-4, IL-8, TNF-α, INF-γ against the background of a decrease in IL-1β and IL-2. At the same time, an increase in the concentration of CA 19-9 was accompanied by a decrease in the levels of IL-8 and INF-γ, which may lead to the preservation of cancer risks.&#x0D; Thus, the assessment of changes in the content of markers of oncopathology, inflammatory mediators and their relationships among workers in the production of VC and PVC indicates and confirms the role of violations of the mechanisms of immunoregulation underlying the formation of various pathologies, including oncological ones. Further study of the mechanisms of cytokine regulation of the antitumor immune response will contribute to improving the methods of early diagnosis and prevention of disorders in the body of workers at carcinogenic enterprises.&#x0D; Ethics. The study was conducted in compliance with Ethical standards in accordance with the Helsinki Declaration of the World Medical Association.

Carbohydrate antigen 125: a useful marker of congestion, fibrosis, and prognosis in heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a disease associated with high morbidity and mortality, for which it is difficult to identify patients with the poorest prognosis in routine clinical practice. Carbohydrate antigen 125 (CA 125) has been shown to be a potential marker of congestion and prognosis in HF. We sought to better characterize HFpEF patients with high CA 125 levels by using a multimodal approach. We prospectively enrolled 139 HFpEF patients (78±8years; 60% females) and 25 controls matched for age and sex (77±5years; 60% females). They underwent two-dimensional echocardiography, cardiac magnetic resonance with late gadolinium enhancement [including extracellular volume (ECV) measurement], and serum measurements of CA 125 level. The primary endpoint of the study was a composite of all-cause mortality or first HF hospitalization. The prognostic impact of CA 125 was determined using Cox proportional hazard models. Median CA 125 levels were significantly higher in HFpEF patients compared with controls [CA 125: 23.5 (14.5-44.7) vs. 14.6 (10.3-21.0) U/mL, P=0.004]. CA 125 levels were positively correlated with a congestion marker [N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, Pearson's r=0.37, P<0.001] and markers of cardiac fibrosis estimated by both ECV (Pearson's r=0.26, P=0.003) and fibroblast growth factor 23 levels (Pearson's r=0.50, P<0.001). Over a median follow-up of 49 (22-64) months, 97 HFpEF patients reached the composite endpoint. Even after adjustment for the Meta-Analysis Global Group in Chronic risk score, a CA 125 level ≥35U/mL was still a significant predictor of the composite endpoint [hazard ratio (HR): 1.58 (1.04-2.41), P=0.032] and more particularly of HF hospitalization [HR: 1.81 (1.13-2.92), P=0.014]. In contrast, NT-proBNP levels were not an independent predictor. CA 125 levels were significantly higher in HFpEF patients compared with controls matched for age and sex and were associated with markers of congestion and cardiac fibrosis. CA 125 levels were a strong and independent predictor of HF hospitalization in HFpEF patients. These data suggest a potential value of CA 125 as a biomarker for staging and risk prediction in HFpEF.

A case of hereditary breast and ovarian cancer syndrome of initially presented as cancer of unknown primary with lymph node metastases unveiled by genetic analysis

Cancer of unknown primary (CUP) is a heterogeneous disease concept involving various malignant tumors. Understanding its pathophysiology is often difficult, together with its treatment. Here, we present a case of CUP with abdominal lymph node enlargement and elevated carbohydrate antigen 125 levels. It initially resembled a favorable prognosis type similar to ovarian cancer, but metastases were observed in cervical lymph nodes, indicating a somewhat atypical CUP compared to the typical ovarian cancer-like CUP. We identified a germline Breast Cancer 1 (BRCA1) p.L63* variant through a family history inquiry and BRCA analysis, indicating hereditary breast and ovarian cancer syndrome. The patient achieved near-complete remission with platinum-based therapy followed by poly (ADP-ribose) polymerase (PARP) inhibitor. The variant has shown sensitivity in both clinical and pathogenic reports in the ClinVar database of the National Institutes of Health. No clinical studies reported on the efficacy of PARP inhibitors specific to this variant, but our case demonstrated the sensitivity of platinum-based therapy followed by PARP inhibitor. Reports of CUP in hereditary breast and ovarian cancer syndrome are very rare, with only a single report in the literature.

Stability of ten serum tumor markers after one year of storage at-18°C.

The storage of serum tumor markers (STM) at-18 °C for one year has been a legal requirement in France since 1999, but has been abolished in 2022. This raises the question of the relevance of maintaining these biobanks in terms of conditions of storage. These should only be implemented after validation; in order to maintain the integrity of the biological sample and must be controlled over time according to the laboratory's procedures. The aim of the study was to assess the suitability of storing 10 STMs by evaluating their stability after one year of storage at-18 °C. A new immuno-enzymatic assay (A+1) was conducted on samples that had been stored at-18 °C for one year after an initial assay (A)of one of the following STMs: carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), total (TPSA), and free (FPSA) prostate-specific antigen, calcitonin (CT), thyroglobulin (TG), and neuro-specific enolase (NSE). The results were confronted to four different permissible error sources. In total, 1148 A+1 assays were performed. A strong correlation between A+1 and A values was found for all analytes, but with a statistically significant reduction in the mean A+1 concentration compared to the mean A concentration in 7/10 STMs. The bias induced by conservation seems to be technically unsustainable if we rely on the repositories closest to the current analytical performances. These results support the discontinuation of mandatory STM biobank storage at-18 °C, which requires considerable technical time and organizational effort.

Simultaneous determination of α-fetoprotein and carbohydrate antigens 125 and 19–9 in potential- and spectrum-resolved dual-mode electrochemiluminescence

Herein, a 3-channel band-bass filter (BPF) turntable was proposed to perform electrochemiluminescence (ECL) multiplexing immunoassay (MIA) in the spectrum- and potential-resolved determinations in a normal ECL analyzer. The simultaneous quantification of α-fetoprotein (AFP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19–9 (CA19-9) was achieved in one cathodic potential scan run. Stopped the BPF turntable at the indicator channel, AFP was determined in the potential range from 0 to –0.8 V by using perylene tetracarboxylic acid@ carboxylic carbon nanotubes (Ep = –0.43 ∼ –0.45 V) as the ECL tag, with the limit of detection (LOD) of 0.53 fg mL−1. During the potential scanned from –0.8 to –1.6 V then back –0.8 V, the BPF turntable was rotated to perform the spectrum-resolved ECL MIA for CA125 and CA19-9, with nanocrystals of CdSe (λmax = 550 nm) and CdTe (λmax = 750 nm) as the ECL tags, respectively. A simple accumulative algorithm was used to obtain stable ECL intensity for spectrum measurement and enhance the sensitivity in ECL MIA. The LODs for CA125 and CA19-9 were 0.058 and 0.11 mU mL−1, respectively, which are close to those in the single immunoassays. The combination of the specially designed BPF turntable and single photomultiplier tube detector offers high sensitivity in the spectrum-resolved ECL biosensors.

Long-term sustained clinical remission of peritoneal metastatic pancreatic ductal adenocarcinoma after sequential chemoradiation therapy: a case report

Patients with peritoneal metastatic pancreatic ductal adenocarcinoma (pmPDAC) with high-level serum carbohydrate antigens (CAs) always suffer extremely dismal prognosis, with a median survival of several months. Herein, we reported a case of pmPDAC with high serum CAs who had long-term clinical remission with normalization of CAs after chemoradiation. In November 2019, a 64-year-old male patient was admitted to our center with a solid mass measuring 2.8 × 2.5 × 2.0 cm in the body of the pancreas near the celiac trunk. Positron emission tomography-computed tomography (PET-CT) revealed an standardized uptake value max (SUVmax) of 4.2. The serum CA 242 level exceeded 150.0 U/mL (normal range: 0–20 U/mL), and CA 19-9 was elevated at 975.2 U/mL (normal range: 0–34 U/mL). During laparotomy, the tumor was found to encircle the celiac trunk over 180°, with several small peritoneal nodules in the lesser omental cavity. Pathological examination confirmed the diagnosis of pmPDAC. Next-generation sequencing revealed RAS G12V, EGFR mutation (-), low tumor mutation burden (TMB), and microsatellite stability (MSS). The patient underwent 6 cycles of the AG regimen (gemcitabine plus nab-paclitaxel), resulting in significant tumor shrinkage and a sharp decline in CAs. Partial remission was achieved. However, due to intolerant neurotoxicity, the AG regimen was discontinued. Subsequently, synchronous oral fluorouracil (S1) and radiation therapy were administered. Five months after radiation treatment, all CAs normalized. Oral S1 was continued for an additional 3 months. Eventually, all anti-cancer drugs were stopped. Computed tomography scans indicated that the tumor still surrounded the celiac trunk and common hepatic artery. After a thorough discussion, a wait-and-see strategy was adopted. Remarkably, 32 months after stopping anti-cancer medication, the patient remains in good health, with sustained normalization of CAs. At the last follow-up, he had lived for 50 months, and the normalization of the CAs was sustained for 36 months. Although he still suffers the risk of disease progression, it is a successful case of state-of-the-art chemoradiation for a dismal pmPDAC patient.

Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study.

Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.

Carbohydrate antigen 125-guided pre-TAVI medical optimization: impact on quality of life and clinical outcomes

Introduction and objectivesCarbohydrate antigen 125 (CA125), a biomarker associated with fluid overload, has proven useful in managing diuretic therapy in heart failure. We aimed to evaluate the impact of diuretic optimization guided by CA125 before transcatheter aortic valve implantation (TAVI) on outcomes. MethodsThis prospective interventional study enrolled patients scheduled for TAVI, in whom baseline CA125 was measured 2 weeks before TAVI. Patients with CA125 ≥ 20 U/mL underwent diuretic up-titration before TAVI. Three groups were included: group I) baseline CA125 <20 U/mL; IIa) CA125 ≥ 20 U/mL that decreased after treatment, and IIb) CA125 ≥ 20 U/mL that did not decrease. The primary outcome was changes in the Kansas City Cardiomyopathy Questionnaire at 3 and 12 months. The secondary endpoint was clinical events. ResultsThe study included 184 patients (115 group I, 46 IIa, and 23 IIb). Groups I and IIa exhibited early and sustained improvements in the Kansas City Cardiomyopathy Questionnaire (group I: 18.9 points [95%CI, 15.7-22.1; P <.001] at 90 days, and 18.1 [95%CI, 14.9-21.4, P <.001] at 1 year; group IIa: 21.1 points [95%CI, 15.4-26.7; P <.001] and 19.5 [95%CI, 13.9-25.1; P <.001] respectively). In contrast, in group IIb there was no significant improvement at 90 days (P=.12), with improvement being significant only at 1 year (17.8 points, 95%CI, 5.9-29.6; P=.003). Over a median follow-up of 20.7 months, there were 63 (27.83%) deaths or heart failure admissions. Multivariate analysis showed a lower risk of events in group I vs IIb (HR, 0.28; 95%CI, 0.14-0.58; P <.001), and IIa vs IIb (HR, 0.24; 95%CI, 0.11-0.55; P <.001). ConclusionsPatients with persistently high CA125 despite diuretic therapy pre-TAVI showed slower functional recovery and poorer clinical outcomes after TAVI.

Clinicopathological Impact of High Preoperative CA19-9 in Early-stage Colorectal Cancer: A Single-center Retrospective Cohort Study.

This study examined the clinical significance of very high preoperative carbohydrate antigen 19-9 (CA19-9) levels in patients with early-stage colorectal cancer (CRC). We retrospectively analyzed the clinicopathological data of patients who underwent curative resection for primary CRC (c-Stage I-III) between 2004 and 2022 in our facility. The patients were classified into three groups according to the preoperative CA19-9 level: normal (≤37.0 U/ml), high (>37.0 to ≤100.0 U/ml), and very high (>100.0 U/ml). Of 971 patients, 885 (91.1%), 67 (6.9%), and 19 (2.0%) had normal, high, and very high CA19-9 levels, respectively. Overall survival (very high vs. normal: p<0.0001, very high vs. high: p=0.01) and recurrence-free survival (very high vs. normal: p<0.0001, very high vs. high: p=0.18) were significantly worse in the very high group. On multivariate analysis including TNM stage, very high preoperative CA19-9 levels were independently associated with worse overall (odds ratio=4.54; 95% confidence interval=2.03-10.16; p=0.0002) and recurrence-free survival (odds ratio=3.49; 95% confidence interval=1.82-6.69; p=0.0002). High preoperative CA19-9 levels were associated with poor survival in early-stage CRC. Careful intraoperative observation and close follow-up might be necessary.

Can preoperative Carbohydrate Antigen 19-9 predict metastatic pancreatic cancer? Results of a systematic review and meta-analysis

BackgroundTo investigate the relationship between preoperative Carbohydrate Antigen19-9(CA19-9)and pancreatic cancer occult metastasis. MethodsSystematic search of MEDLINE, CENTRAL, Web of Science and bibliographic reference lists were conducted. All comparative observational studies investigating the predictive ability of preoperative CA 19-9 in patients with pancreatic cancer were considered. Mean CA-19-9 value in the pancreatic cancer patients with and without metastasis were evaluated. Best cut-off value of CA 19-9 for metastasis was determined using ROC analysis. ResultsTen comparative observational studies reporting a total of 1431 pancreatic cancer patients with (n = 496) and without (n = 935) metastasis were included. Subsequent meta-analysis demonstrated that mean preoperative CA 19-9 level was significantly higher in patients with metastases compared to those without (MD: 904.4; 95 % CI, 642.08–1166.74, P < 0.0001). The between-study heterogeneity was significant (I2: 99 %, P < 0.00001). ROC analysis yielded a cut-off CA 19-9 level of 336 with a sensitivity and specificity for predicting metastasis of 90 % and 80 %, respectively (AUC = 0.90). ConclusionsCA 19-9 level is significantly higher in patients with metastatic pancreatic cancer. A preoperative CA 19-9 value of 336 should be considered as an acceptable cut-off value to design prospective studies.

Siah2 inhibitor and the metabolic antagonist Oxamate retard colon cancer progression and downregulate PD1 expression.

Solid tumors such as colon cancer are characterized by rapid and sustained cell proliferation, which ultimately results in hypoxia, induction of hypoxia-inducible factor-1α (HIF-1α), and activation of glycolysis to promote tumor survival and immune evasion. We hypothesized that a combinatorial approach of menadione (MEN) as an indirect HIF-1α inhibitor and sodium oxamate (OX) as a glycolysis inhibitor may be a promising treatment strategy for colon cancer. We investigated the potential efficacy of this combination for promoting an antitumor immune response and suppressing tumor growth in a rat model of colon cancer. Colon cancer was induced by once-weekly subcutaneous injection of 20 mg/kg dimethylhydrazine (DMH) for 16 weeks. Control rats received the vehicle and then no further treatment (negative control) or MEN plus OX for 4 weeks (drug control). Dimethylhydrazine-treated rats were then randomly allocated to four groups: DMH alone group and other groups treated with MEN, OX, and a combination of (MEN and OX) for 4 weeks. Serum samples were assayed for the tumor marker carbohydrate antigen (CA19.9), while expression levels of HIF-1α, caspase-3, PHD3, LDH, and PD1 were evaluated in colon tissue samples by immunoassay and qRT-PCR. Additionally, Ki-67 and Siah2 expression levels were examined by immunohistochemistry. The combination of MEN plus OX demonstrated a greater inhibitory effect on the expression levels of HIF-1α, Siah2, LDH, Ki-67, and PD1, and greater enhancement of caspase-3 and PHD3 expression in colon cancer tissues than either drug alone. Simultaneous targeting of hypoxia and glycolysis pathways by a combination of MEN and OX could be a promising therapy for inhibiting colon cancer cell growth and promoting antitumor immunity [1].

Effect of Paxillin Expression and Phosphorylation on Colorectal Cancer Prognosis and Metastasis.

Colorectal cancer (CRC) is the third most common cancer worldwide, and metastasis is strongly associated with poor prognosis in patients with CRC. We have previously found that the expression and phosphorylation of paxillin (PXN) play an important role in the metastatic potential of breast cancer. This study examined the potential role of PXN in CRC metastasis. Resected tumor specimens from 92 patients with CRC were subjected to immunohistochemical analysis of PXN levels. Three human CRC cell lines, HCT116, LoVo, and SW480 were used for scratch and transwell invasion assays to examine the effects of PXN over-expression. RNA sequencing was performed to obtain the expression profiles under PXN over-expression. High levels of PXN were significantly correlated with advanced stage, higher carcinoembryonic antigen and carbohydrate antigen 19-9 levels, and poorer overall survival. The migration ability of CRC cells was enhanced by exogenous PXN over-expression, but this enhancement was not observed in cells harboring exogenously mutated PXN at Tyr31 or Tyr88 phosphorylation sites. In PXN-over-expressing cells, TNF-α signaling via NF-[Formula: see text]B was positively enriched. PXN expression and phosphorylation at Tyr31 or Tyr88 may influence the migration and invasion of CRC cells. PXN expression and phosphorylation at Tyr31 or Tyr88 are promising targets for evaluating prognosis and treating CRC.

Integration of pretreatment tumor markers in a nomogram model for prognostic prediction of FIGO stage I endometrial cancer: A multi-institutional cohort study.

Traditionally, the prognosis of patients with FIGO stage I endometrial cancer is determined by clinicopathological risk factors. In this study, we assessed the potential contribution of pretreatment carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) levels to estimating the prognosis of these patients and aimed to develop and validate a prognostic nomogram. This retrospective study included patients with FIGO stage I endometrial cancer who underwent treatment between January 2009 and December 2021 in the four institutes of Chang Gung Memorial Hospital. To identify optimal cutoff values of CEA and CA-125 for predicting survival, receiver operating characteristic (ROC) curves were generated, the Kaplan-Meier method was used to estimate survival, and a Cox regression model was used to analyze the independent prognostic factors. Finally, a nomogram and calibration curve were constructed to predict patient survival probability. Of the 1559 patients evaluated, the optimal cutoff values of CEA and CA-125 were 1.44 ng/mL (area under the ROC curve [AUC] 0.601) and 39.77 U/mL (AUC 0.503), respectively. Multivariate Cox regression analysis showed that pretreatment CEA (hazard ratio [HR] 2.11, 95% confidence interval [95% CI] 1.35-3.28), CA-125 (HR 2.07, 95% CI 1.31-3.27), age >70 years (HR 12.54, 95% CI 5.05-31.11), myometrial invasion >50% (HR 1.69, 95% CI 1.03-2.73), non-endometrioid histology (HR 1.83, 95% CI 1.14-2.95), high-grade tumor (HR 2.41, 95% CI 1.46-3.97), and lymphovascular space invasion (HR 2.32, 95% CI 1.26-4.25) were significant variables associated with overall survival. These factors were used to construct the nomogram model, which showed good concordance and accuracy. Integration of pretreatment CEA and CA-125 in a prognostic nomogram is feasible. Our prediction model has the potential to assist clinicians in guiding appropriate clinical practice.