• Hepatocellular carcinoma
• diagnostic model
• microvascular invasion

• Humans
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/surgery
• Liver Neoplasms/pathology
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Liver Neoplasms/surgery
• Male
• Female
• Middle Aged
• Neoplasm Invasiveness/diagnosis
• Neoplasm Invasiveness/pathology
• Risk Factors
• Microvessels/pathology
• Biomarkers, Tumor/blood
• ROC Curve
• Aged
• alpha-Fetoproteins/analysis
• Retrospective Studies
• Adult
• Prothrombin/analysis
• Protein Precursors/blood
• Liver/pathology
• Liver/blood supply
• Biomarkers

Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer and was the third leading cause of cancer-related deaths worldwide in 2020.

To evaluate the diagnostic potential of key tumor markers in serum, bile, and fecal samples for detecting HCC.

Blood, bile, and fecal samples were collected from patients (n = 265) with HCC and cholecystitis from Guangxi Medical University’s First Affiliated Hospital. Immunohistochemistry was performed on 69 HCC samples, and 16S ribosomal RNA sequencing was conducted on 166 fecal samples. Tumor marker cut-off values in bile and feces were determined using the Youden index, while serum biomarkers followed hospital standards. Diagnostic performance was evaluated using receiver operating characteristic analysis.

The areas under the curve (AUCs) for distinguishing HCC were 0.898, 0.904, and 0.859 for serum alpha-fetoprotein (AFP), prothrombin induced by vitamin K absence-II (PIVKA-II), and bile AFP, respectively. Serum AFP had the highest diagnostic value (80%) for early-stage HCC. Combination analysis found that bile AFP and serum PIVKA-II achieved the highest AUC of 0.965 (P < 0.001), suggesting that bile AFP may serve as a valuable complementary biomarker, particularly in cases where serum AFP is not significantly elevated. Additionally, bile AFP was positively correlated with Actinomyces, which plays a significant role in promoting tumorigenesis; and was negatively correlated with Faecalibacterium, which was associated with robust anticancer immune responses (P < 0.05). These findings suggest the potential role of gut microbiota in modulating AFP levels and HCC progression.

Bile AFP improved the sensitivity of HCC detection, with the combination of bile AFP and PIVKA-II demonstrating the highest AUC for HCC diagnosis. AFP is associated with poorer clinical outcomes.

• Hepatocellular carcinoma
• Alpha-fetoprotein
• Prothrombin induced by vitamin K absence-II
• Bile biomarkers
• Serum biomarkers
• Diagnosis
• Receiver operating characteristic analysis
• Gut-liver axis

• endometrial cancer
• hepatic steatosis index
• nonalcoholic fatty liver disease

• Cytokeratin 19
• Hepatocellular carcinoma (HCC)
• Nomogram model
• Optimal cut-off value
• Prognosis

• Humans
• Keratin-19/metabolism
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/metabolism
• Liver Neoplasms/diagnosis
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/diagnosis
• Male
• Female
• Middle Aged
• Prognosis
• Nomograms
• Biomarkers, Tumor/metabolism
• Adult
• ROC Curve
• Aged
• Disease-Free Survival
• Retrospective Studies

• GXMUYSF202407 High-level Innovation Team and Outstanding Scholar Program in Guangxi Colleges and Universities, Youth Science Foundation of Guangxi Medical University
• 82260573/81960450 National Natural Science Foundation of China
• GKE-ZZ202215 Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor, Ministry of Education/Guangxi, Independent Research Project
• AA18221001, AB18050020 Guangxi Key Research and Development Program

• depth of tumor invasion
• epithelial ovarian cancer
• human epididymal protein 4
• postoperative recurrence and metastasis

• Humans
• Female
• Carcinoma, Ovarian Epithelial/pathology
• Carcinoma, Ovarian Epithelial/metabolism
• Carcinoma, Ovarian Epithelial/surgery
• WAP Four-Disulfide Core Domain Protein 2/analysis
• WAP Four-Disulfide Core Domain Protein 2/metabolism
• Middle Aged
• Neoplasm Recurrence, Local/metabolism
• Neoplasm Recurrence, Local/pathology
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/surgery
• Prognosis
• Neoplasm Invasiveness
• Adult
• Biomarkers, Tumor/metabolism
• Aged
• Neoplasm Metastasis

• cancer of unknown primary
• nomogram
• prognosis
• spinal metastasis
• survival prediction

• National Key Research and Development Project of China
• The Shanghai Science and Technology Committee
• The Logistics Support Department of PLA
• Youth Doctor Assistance Program Funds of Shanghai Changzheng Hospital (Minglei Yang)

• autoantibodies
• early cancer detection
• exosomes
• liquid biopsies
• mucin biomarker

• R01 CA206444 NCI NIH HHS
• U01 CA200466 NCI NIH HHS
• R01 CA247471 NCI NIH HHS
• R44 DK117472 NIDDK NIH HHS
• P01 CA217798 NCI NIH HHS
• R01 CA195586 NCI NIH HHS
• U01 CA213862 NCI NIH HHS
• R01 CA218545 NCI NIH HHS
• R01 CA241752 NCI NIH HHS
• U01 CA210240 NCI NIH HHS
• I01 BX004676 BLRD VA

Cancer antigen 125 (CA125) is clinically used to monitor response to therapy in ovarian cancer and has been proposed for use in detecting ovarian cancer. This population-based study examines how demographic characteristics, gynecologic/reproductive history, chronic non-malignant medical conditions, history of non-ovarian cancer, lifestyle practices, and biomarkers of inflammation correlate with serum CA125 in both premenopausal and postmenopausal women without ovarian cancer across the United States.

Participants were identified from the National Health and Nutrition Examination Survey 2001–2002. Linear and logistic regression models were applied.

Higher CA125 levels were found to correlate with younger age, Non-Hispanic White race/ethnicity, and lower body mass index. In premenopausal women (N = 1157), current smoking was associated with lower CA125 (− 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5–10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. In postmenopausal women (N = 1116), coronary artery disease (CAD) history was associated with higher CA125 (28.27%, p = 0.047) by multivariable linear regression; history of CAD (OR = 5.00, p = 0.011), history of breastfeeding (OR = 2.46, p = 0.026), and increased CRP level (OR = 1.41, p = 0.042) were more likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression.

Results suggest CA125 is lower in premenopausal women who are current smokers and OCP users of moderately longer duration but higher in those with non-ovarian cancer. CA125 is higher in those postmenopausal women with CAD, history of breastfeeding and elevated CRP level. These associations can inform clinical interpretation of individual patients’ CA125 levels.

The online version contains supplementary material available at 10.1186/s12885-022-09637-7.

• CA125
• Epidemiology
• Ovarian cancer

• CA125
• Hilar cholangiocarcinoma
• Prognosis

The association between the serum levels of cancer antigen 125 (CA125; also termed MUC16) and the prognosis of patients with hepatocellular carcinoma (HCC) has not been widely reported to date. The aim of the present study was to determine the association between preoperative serum CA125 levels and prognosis of patients with hepatitis B virus (HBV)-related HCC after hepatectomy. The study included 306 patients with HBV-related HCC who underwent liver resection and were classified into four subgroups based on their baseline CA125 and α-fetoprotein (AFP) levels. The perioperative clinical data were compared and analyzed. Kaplan-Meier and Cox regression analyses were performed to determine the associations between patient clinicopathological characteristics and survival. The results revealed that the median follow-up time was 35 months. Patients with low preoperative serum CA125 levels presented with improved 3-year disease-free survival (DFS) (79.3 vs. 75.7%; P=0.278) and overall survival (OS) (84.4 vs. 77.1%; P=0.001) rates compared with those among patients with high preoperative serum CA125 levels. High preoperative serum CA125 levels were a risk factor associated with short DFS and OS rates in all patients. In patients with baseline AFP levels >100 ng/ml, low preoperative serum CA125 levels were significantly associated with prolonged DFS and OS rates (log-rank test P=0.002 and P=0.005, respectively). In patients with AFP levels ≤100 ng/ml, no significant differences were observed in DFS or OS rates between the high and low preoperative serum CA125 groups. Patients with high preoperative serum CA125 and AFP levels exhibited the worst prognosis (low DFS and OS rates). In conclusion, high baseline CA125 levels may be associated with a poor prognosis in patients with HBV-related HCC.

• HBV-related HCC
• cancer antigen 125
• hepatectomy
• α-fetoprotein

Patients with hepatitis B virus (HBV) infection are at high risk of hepatocellular carcinoma (HCC). This study aimed to evaluate the expression of microRNA-324-3p (miR-324-3p) in HBV-related HCC and explore the clinical significance of serum miR-324-3p and other available biomarkers in the diagnosis and prognosis of HBV-related HCC.

Expression of miR-324-3p in HBV infection–related cells and patients was estimated using quantitative real-time polymerase chain reaction (PCR). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of serum miR-324-3p, alpha-fetoprotein (AFP), and protein induced by vitamin K absence/antagonist II (PIVKA-II) in the differentiation of HBV-related HCC from healthy controls and chronic hepatitis B patients (CHB). The relationship between serum miR-324-3p and patients’ clinical features was assessed using the chi-square test, and the value of miR-324-3p to predict overall survival prognosis was evaluated using Kaplan-Meier methods and Cox regression assay in patients with HBV-related HCC.

HBV-related HCC cells had significantly increased miR-324-3p compared with normal and HBV-unrelated HCC cells, and serum miR-324-3p in HCC patients with HBV infection was also higher than that in healthy controls and CHB. Serum miR-324-3p had relatively high diagnostic accuracy for the screening of HCC cases with HBV infection, and the combination of miR-324-3p, AFP, and PIVKA-II showed improved diagnostic performance. Additionally, high-serum miR-324-2p in HBV-related HCC patients was associated with cirrhosis, tumor size, clinical stage, and poor overall survival prognosis.

High-serum miR-324-3p may be involved in the progression of HBV-related hepatitis to HCC and may serve as a candidate biomarker for the diagnosis and prognosis of HBV-related HCC.

• diagnosis
• hepatitis B virus
• hepatocellular carcinoma
• microRNA-324-3p
• prognosis