Diagnostic value of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in serum, bile, and feces in hepatocellular carcinoma.

BACKGROUND

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.

AIM

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

METHODS

Blood, bile, and fecal samples were collected from patients ( = 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.

RESULTS

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 ( < 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 , which plays a significant role in promoting tumorigenesis; and was negatively correlated with , which was associated with robust anticancer immune responses ( < 0.05). These findings suggest the potential role of gut microbiota in modulating AFP levels and HCC progression.

CONCLUSION

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.