Chinese Study Finds Serum MicroRNA Classifier Better Than Alpha-Fetoprotein for Early Detection of Hepatocellular Carcinoma


Key Points

  • The miRNA classifier was more accurate than alpha-fetoprotein in detecting preclinical hepatocellular carcinoma.
  • The classifier was more accurate in detecting small and early-stage hepatocellular carcinoma.

In a study reported in The Lancet Oncology, Lin et al developed a serum microRNA classifier that was more accurate than alpha-fetoprotein in detecting preclinical hepatocellular carcinoma.

Study Details

The study involved healthy controls, inactive hepatitis B surface antigen carriers, individuals with chronic hepatitis B, individuals with hepatitis B-induced liver cirrhosis, and patients with diagnosed hepatocellular carcinoma from four hospitals in China. There were 257 participants in the training cohort, and 352 and 139 participants in two independent validation cohorts; in a third validation cohort, 27 patients with hepatocellular carcinoma and 135 matched controls were included in a nested case-control study.

The identified micro RNA classifier contained seven differentially expressed micro RNAs (miR-29a, miR-29c, miR-133a, miR-143, miR-145, miR-192, and miR-505). It was compared with alpha-fetoprotein at a cutoff of 20 ng/mL (alpha-fetoprotein–20) using receiver operating characteristic area under the curve (AUC).

Preclinical, Small, and Early-Stage Disease

The micro RNA classifier was more accurate in distinguishing hepatocellular carcinoma from controls in the two validation cohorts (AUCs = 0.817 vs 0.709 and 0.884 vs 0.796, both P < .05) but not in the training cohort (AUCs = 0.825 vs 0.814, P = .72). Across all four cohorts, micro RNA classifier sensitivity for hepatocellular carcinoma (range = 70.4%–85.7% vs 40.7%–69.4%) but not specificity (range = 80.0%–91.1% vs 84.9%–100%) was greater than alpha-fetoprotein–20.

In the nested case-control study, the sensitivity of the micro RNA classifier vs alpha-fetoprotein–20 for hepatocellular carcinoma was 29.6% vs 7.4% at 12 months before clinical diagnosis, 48.1% vs 11.1% at 9 months, 48.1% vs 18.5% at 6 months, and 55.6% vs 22.2% at 3 months (all P < .05).

The micro RNA classifier was more accurate than alpha-fetoprotein–20 in identifying small (AUC = 0.833 vs 0.727, P = .0018) and early-stage hepatocellular carcinoma (AUC = 0.824 vs 0.754, P = .015) and was also accurate in detecting alpha-fetoprotein–negative hepatocellular carcinoma (AUC = 0.825).

The investigators concluded: [The micro RNA classifier] is a potential biomarker for hepatocellular carcinoma, and can identify small-size, early-stage, and [alpha-fetoprotein]–negative hepatocellular carcinoma in patients at risk. The [micro RNA] classifier could be valuable to detect preclinical hepatocellular carcinoma, providing patients with a chance of curative resection and longer survival.”

Shi-Mei Zhuang, PhD, of The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, is the corresponding author for the Lancet Oncology article.

The study was funded by the National Key Basic Research Program, National Science and Technology Major Project, National Natural Science Foundation of China.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.