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Prognostic Molecular Indices of Resectable Hepatocellular Carcinoma: Implications of S100P for Early Recurrence

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Abstract
Background: Although hepatocellular carcinomas (HCCs) often recur in patients undergoing hepatectomy, there are no reliable biomarkers of this undesirable event. Recent RNA-based efforts have developed valuable genetic indices prognostic of cancer outcomes. We aimed to identify molecular predictors of early recurrence after resection of HCC, and reveal the genomolecular structure of the resected tumors.

Method: Based on the transcriptomic and genomic datasets of 206 HCC samples surgically resected in the Asan Medical Center (AMC), we performed a differential gene expression analysis to identify quantitative markers associated with early recurrence and used the unsupervised clustering method to classify genomolecular subtypes.

Results: Differential gene expression profiling revealed that S100P was the highest-ranked overexpressed gene in HCCs that recurred within 2 years of surgery. This trend was reproduced in immunohistochemical studies of the original cohort and an independent AMC cohort. S100P expression also independently predicted HCC-specific mortality post-resection (adjusted hazard ratio 1.09, 95% confidence interval 1.01-1.19; p = 0.042). Validation in a Chinese cohort and in in vitro experiments confirmed the prognostic value of S100P in HCC. We further identified five discrete molecular subtypes of HCC; a subtype with stem cell features ('AMC-C4') was associated with the worst prognosis, both in our series and another two Asian datasets, and S100P was most strongly upregulated in that subtype.

Conclusion: We identified a promising prognostic biomolecule, S100P, associated with early recurrence after HCC resection, and established the genomolecular architecture of tumors affecting clinical outcomes, particularly in Asian patients. These new insights into molecular mediators should contribute to effective care for affected patients.
Author(s)
강효정김원경성창옥심주현안지현오보라오유진오지혜유은실황희상
Issued Date
2021
Type
Article
Keyword
AnalysisGene expressionLiver cancerMedicineMedicine & Public HealthOncologyRNAsurgerySurgical OncologyTranslational Research
DOI
10.1245/s10434-021-09825-y
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8216
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2507667696&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Prognostic%20Molecular%20Indices%20of%20Resectable%20Hepatocellular%20Carcinoma:%20Implications%20of%20S100P%20for%20Early%20Recurrence&offset=0&pcAvailability=true
Publisher
ANNALS OF SURGICAL ONCOLOGY
Location
미국
Language
한국어
ISSN
1068-9265
Citation Volume
28
Citation Number
11
Citation Start Page
6466
Citation End Page
6478
Appears in Collections:
Medicine > Medicine
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