A Viral Exposure Signature Defines Early Onset of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy with its global incidence and mortality rate continuing to rise, although early detection and surveillance are suboptimal. We performed serological profiling of the viral infection history in 899 individuals from an NCI-UMD case-control study using a synthetic human virome, VirScan. We developed a viral exposure signature and validated the results in a longitudinal cohort with 173 at-risk patients who had long-term follow-up for HCC development. Our viral exposure signature significantly associated with HCC status among at-risk individuals in the validation cohort (area under the curve: 0.91 [95% CI 0.87-0.96] at baseline and 0.98 [95% CI 0.97-1] at diagnosis). The signature identified cancer patients prior to a clinical diagnosis and was superior to alpha-fetoprotein. In summary, we established a viral exposure signature that can predict HCC among at-risk patients prior to a clinical diagnosis, which may be useful in HCC surveillance.

Serological Responses to Human Virome Define Clinical Outcomes of Italian Patients Infected with SARS-CoV-2

“…We have recently employed a synthetic virome technology, VirScan, to detect the exposure history to most known human viruses ( Liu et al, 2020 ). VirScan applies a phage display library that covers 96,179 viral peptides that are each 56 residues in length tilling the protein sequences with 28 residues overlaps, which corresponds to 206 viral species and 1,276 human viral strains ( Xu et al, 2015 ).…”

“…VirScan applies a phage display library that covers 96,179 viral peptides that are each 56 residues in length tilling the protein sequences with 28 residues overlaps, which corresponds to 206 viral species and 1,276 human viral strains ( Xu et al, 2015 ). Using this technology, we developed a viral exposure signature (VES) that could discriminate liver cancer patients from at-risk or healthy individuals and validated the results in a longitudinal cohort with at-risk patients who had long-term follow-up for liver cancer development ( Liu et al, 2020 ). Remarkably, VES could predict cancer among at-risk patients prior to a clinical diagnosis and appeared clinically applicable for liver cancer surveillance.…”

Long-term prognosis and management of hepatocellular carcinoma after curative treatment

“…Thus, exposure to both hepatitis virus and other viruses can affect hepatocarcinogenesis. 11 For example, keratin strains of influenza virus trigger the emergence of HCC, whereas human respiratory syncytial virus and human rhinovirus 23 are depleted in the HCC cohort. 11 This might be useful in selecting patients with risk for late recurrence after curative treat- http://www.e-cmh.org https://doi.org/10.3350/cmh.2020.0208 For adjuvant therapy after curative treatment, several trials have been conducted to date and a few are still in process ( Table 1).…”

“…11 For example, keratin strains of influenza virus trigger the emergence of HCC, whereas human respiratory syncytial virus and human rhinovirus 23 are depleted in the HCC cohort. 11 This might be useful in selecting patients with risk for late recurrence after curative treat- http://www.e-cmh.org https://doi.org/10.3350/cmh.2020.0208 For adjuvant therapy after curative treatment, several trials have been conducted to date and a few are still in process ( Table 1). The result of phase 3 clinical trial that examines the efficacy of sorafenib in adjuvant setting revealed no difference in the recurrence-free survival between sorafenib and placebo groups.…”

Towards personalized screening for hepatocellular carcinoma: Still not there

“…14 Other preliminary data showed that the AA allele of rs6726639 deSNP of MERTK (MER tyrosine kinase) gene, a regulator of tumor-associated macrophages involved in the modulation of inflammatory responses and angiogenesis, is associated with a higher risk of developing HCC after HCV eradication by DAAs in patients with HCV cirrhosis. 15 Finally, Liu et al 16 recently demonstrated that a viral exposure signature is predictive of HCC in at-risk patients who had long-term follow-up for HCC development. These relevant data open a new approach to grade cancer risk that, combined with established parameters, could become the clue to define the absence of HCC risk.…”