Hepatitis B virus pre-S2 deletion (nucleotide 1 to 54) in plasma predicts recurrence of hepatocellular carcinoma after curative surgical resection

Hsu

et al. 2021

JCM

Self Cite

Hepatocellular carcinoma (HCC) is, globally, one of the most prevalent and deadly human cancers; despite curative surgical resection, its high recurrence rate after surgery remains a large threat, resulting in poor patient survival. The hepatitis B virus (HBV) pre-S2 mutant that harbors deletions spanning the pre-S2 gene segment has emerged as an important oncoprotein for HCC development and a valuable prognostic biomarker for HCC recurrence; however, its relationship with clinicopathological factors is largely unexplored. In this study, the correlation of the deletion spanning the pre-S2 gene segment with clinicopathological factors and the association of such correlation with HCC recurrence after curative surgical resection were examined in HBV-related HCC patients. Inverse correlation between serum albumin level and the deletion spanning the pre-S2 gene segment was identified. HCC patients with the presence of the deletion spanning the pre-S2 gene segment and a low serum albumin level were associated with higher HCC recurrence than patients with either factor alone or neither factor were. Moreover, a combination of the serum albumin level and the deletion spanning the pre-S2 gene segment exhibited better performance than that of either factor alone in predicting HCC recurrence. Collectively, this study shows an association of low serum albumin level with pre-S2 mutant-positive HCC patients, and validates the prognostic value of this association in identifying patients with higher HCC recurrence after curative surgical resection.

Section: Introductionmentioning

confidence: 99%

Association of Low Serum Albumin Level with Higher Hepatocellular Carcinoma Recurrence in Patients with Hepatitis B Virus Pre-S2 Mutant after Curative Surgical Resection

Hsu

et al. 2021

JCM

Self Cite

“…Either the presence of deletions spanning the pre-S2 gene segment or a high percentage of pre-S2 plus pre-S1 + pre-S2 gene deletions (or both) were evaluated as an independent biomarker for predicting a higher risk of HCC recurrence [26]. Furthermore, Teng et al used the same approach to determine that the pre-S2 gene deletions at nts 1 to 54 (a 54 nt deletion) were the most frequently detected type of pre-S gene deletions in the plasma, and are a biomarker that independently predicts a higher risk of HCC recurrence after curative surgical resection [27].…”

Section: Ngs-based Detection Of Pre-s Gene Deletions and Its Applicat...mentioning

confidence: 99%

Approaches for Detection of Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins and Their Application in Prediction of Higher Risk of Hepatocellular Carcinoma Development and Recurrence

Lin

et al. 2022

Viruses

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Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide and is closely associated with chronic hepatitis B virus (HBV) infection. Pre-S deleted proteins are naturally occurring mutant forms of HBV large surface proteins that are expressed by HBV surface genes harboring deletion mutations over the pre-S gene segments. It has been well demonstrated that HBV pre-S deleted proteins function as important oncoproteins, which promote malignant phenotypes of hepatocytes through the activation of multiple oncogenic signaling pathways and result in HCC formation. The oncogenic signaling pathways activated by pre-S deleted proteins have been verified as potential therapeutic targets for the prevention of HCC development. Moreover, the presence of pre-S gene deletions and the expression of pre-S deleted proteins in the blood and liver tissues of HBV-infected patients have been evaluated as valuable biomarkers for predicting a higher risk of HCC development and recurrence after curative surgical resection. Therefore, the precise detection of pre-S gene deletions and pre-S deleted proteins holds great promise as regards identifying the patients at higher risk of HCC development and recurrence, thus aiding in more timely and better treatments to improve their survival. This review summarizes the major approaches used for the detection of pre-S gene deletions and pre-S deleted proteins, including the approaches based on Sanger DNA sequencing, pre-S gene chips, next-generation sequencing and immunohistochemistry staining, and it highlights their important applications in the prediction of higher risks of HCC development and recurrence.

“…Furthermore, Teng et al showed that either the presence of deletions spanning the pre-S2 gene segment or a certain percentage of pre-S2 plus pre-S1 + pre-S2 gene deletions (>25%), or a combination of both factors in the blood of HCC patients, was independently associated with higher risk of HCC recurrence after curative surgical resection [ 30 , 31 , 32 ]. Additionally, Teng et al showed that the pre-S2 gene deletion at nts 1 to 54 (a 54 nt deletion) was the most predominant region of pre-S gene deletions in the blood of HCC patients and independently predicted HCC recurrence after curative surgical resection [ 33 ]. Considering that this pre-S2 gene deletion region (nt 1 to 54) coincides with the B-and T-cell epitopes of HBV large surface proteins [ 34 , 35 ], pre-S2 deleted proteins may emerge as immune escape mutants, possibly conferring their growth advantage and explaining their strong association with HCC recurrence.…”

Section: The Presence Of Hbv Pre-s Gene Deletions In the Blood Of Patients With Hcc Is Associated With Higher Risk Of Hcc Recurrence Aftementioning

confidence: 99%

Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins: Clinical and Molecular Implications in Hepatocellular Carcinoma

Lin

Chan

et al. 2021

Viruses

Self Cite

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and therapy.