Detection of Circulating Antibodies to p16 Protein-Derived Peptides in Hepatocellular Carcinoma

Yangchun Xu, MM; Litong Gu, MM; Jiaxin Wang, MD; Zhenqi Wang, MD; Ping Zhang, MD, PhD; Xuan Zhang, MD, PhD


Lab Med. 2020;51(6):574-578. 

In This Article


The CDK inhibitor p16 protein plays a crucial role in cell proliferation regulation via G1-phase cell arrest; thus, its malfunction may result in uncontrolled cell proliferation.[25,26] It is reportedly overexpressed in several cancers.[20,22] In the present study, HCC patients were found to have significantly higher circulating anti-p16 IgG levels than did control subjects. This finding was consistent with those from previous studies where higher circulating anti-p16 IgG levels were observed in cervical,[18] breast,[19] NSCLC,[20,27] and esophageal[21] cancer patients than that of control subjects. Additionally, 2 other studies which applied an ELISA method utilizing recombinant p16 protein for measuring circulating anti-p16 IgG levels found that HCC patients displayed markedly higher anti-p16 IgG levels than did controls.[22,28] The specific mechanism responsible for higher anti-p16 IgG levels in cancer remains unknown; however, this might be owed to higher p16 protein expression in cancer tissues.[29,30] However, hypermethylation-induced p16 expression inhibition is suggested to be a characteristic of HCC patients and is associated with an increased risk of HCC.

Further, plasma anti-p16a IgG levels showed an increasing trend with increasing HCC stage, and advanced- and terminal-stage HCC patients had the highest anti-p16a IgG levels, suggesting that plasma anti-p16 IgG might be a more promising biomarker for HCC prognosis evaluation than early HCC diagnosis. A similar phenomenon was observed in non–small cell lung cancer in a study by Zhang et al,[20] contrary to those in esophageal cancer reported by Jin et al,[21] where circulating anti-p16 IgG levels showed a decreasing trend with increasing tumor stage. Anti-p16 antibody levels are suggestively altered in diverse patterns among cancer types. Nevertheless, there remain several limitations to our work. First, the antibody testing sample size was small, and a large sample size was needed to permit a firm conclusion. Additionally, the control was a poor representative, as the subjects were only recruited from local communities, and reportedly, healthy relatives of HCC patients might be more reliable for identifying a serological biomarker for familial HCC risk.