Hepatit-B virüs ilişkili hepatosellüler karsinomda tümöral glipikan 3 mRNA seviyesinin diagnostik ve prognostik biyobelirteç olabilme potansiyelinin entegratif transkriptomik meta-analiz ve biyoinformatik ile değerlendirilmesi

Sevcan Atay

doi:10.19161/etd.1127225

EN TR

Evaluation of tumoral glypican 3 mRNA level as a diagnostic and prognostic biomarker for hepatitis-b virus-associated hepatocellular carcinoma by an integrative transcriptomic meta-analysis and bioinformatics

Abstract

Aim: The aim of this study is to evaluate the potential of GPC3 mRNA level as a diagnostic and prognostic biomarker for HBV-associated HCC.

Materials and Methods: GPC3 mRNA expression in HBV-associated HCC tumor tissues compared to matched adjacent tissues was evaluated by integrative transcriptomic meta-analysis. The results were validated in a different patient cohort and the possible associations between GPC3 mRNA level and the clinical variables were evaluated.

Results: Transcriptomic data of HBV-associated HCC tissues (n=61) and matched adjacent tissues (n=61) from four datasets (GSE19665;GSE84402;GSE121248;GSE55092) were included in the meta-analysis. GPC3 mRNA level was found to be higher in tumors than adjacent tissues (fold change=12.88; p= 0;FDR=0). The result was validated in GSE14520, (HBV-associated HCC(n)=203; matched adjacent tissue(n)=203), (log-fold-change= 4.82; adj.p=1.43E-79). It was found that GPC3 mRNA level could distinguish HCC from adjacent tissues with high specificity and sensitivity (AUC=0.9108;95%CI=0.08792-0.9424;p<0.0001). There was no association between tumoral GPC3 mRNA level and overall survival (HR (logrank)=0.81;95%CI=0.5223-1.2771;p=0.3663), recurrence within 3 years (p=0.5793), and early, or late recurrence (p= 0.9950). Multivariate Cox proportional hazards regression analyzes also found no association between GPC3 mRNA level and overall survival. High GPC3 mRNA level was associated with high serum AFP level, small tumor size and active viral replication. GPC3 mRNA level was higher at stage 1 than CLIP stage 0 but showed no association with TNM and BCLC staging.

Conclusion: The results of the study suggest that the GPC3 mRNA level has the potential to be a diagnostic biomarker that can work with high specificity and sensitivity in differentiating between HBV-associated HCC and adjacent tissues. However, its potential to be a prognostic biomarker is low.

Keywords

Hepatit-B virüs ilişkili hepatosellüler karsinomda tümöral glipikan 3 mRNA seviyesinin diagnostik ve prognostik biyobelirteç olabilme potansiyelinin entegratif transkriptomik meta-analiz ve biyoinformatik ile değerlendirilmesi

Öz

Amaç: Bu çalışmanın amacı HBV-ilişkili hepatosellüler kansinom hastalarında tümöral GPC3 mRNA seviyesinin diagnostik ve prognostik biyobelirteç olabilme potansiyelinin değerlendirilmesidir.

Gereç ve Yöntem: Eşlenik tümör içermeyen karaciğer dokularına göre HBV-ilişkili HCC tümör dokularında GPC3 mRNA ekspresyonu entegratif transkriptomik meta-analiz yöntemi ile belirlendi. Sonuçlar farklı bir hasta kohortunda valide edildi ve GPC3 mRNA seviyesi ile klinik değişkenler arasındaki ilişki değerlendirildi.

Bulgular: Meta-analize 4 farklı veri setinden (GSE19665;GSE84402;GSE121248;GSE55092) HBV-ilişkili hepatosellüler karsinom dokuları (n=61) ile eşlenik tümör içermeyen dokulara (n=61) ait transkriptomik veriler dahil edildi. GPC3 mRNA seviyesi’nin eşlenik dokulara göre tümörde daha yüksek olduğu bulundu (kat değişimi=12,88; p=0; FDR=0). Sonuçlar GSE14520 veri setinde (HBV-ilişkili HCC tümör (n)=203;eşlenik non-tümöral doku (n)=203) valide edildi (log-kat değişimi= 4,82; adj.p=1, 43 E-79). ROC analizi sonucunda GPC3 mRNA seviyesinin tümör dokularını tümör içermeyen eşlenik karaciğer dokularından yüksek spesifite ve sensitivite ile ayırabildiği bulundu (n=203;AUC=0,9108;%95CI=0,08792-0,9424;p<0,0001). Tümöral GPC3 mRNA seviyesi ile hastalarda genel sağkalım (HR (logrank)= 0,81; %95CI=0,5223-1,2771; p= 0,3663), 3 yıl içinde rekürrans gelişimi (p=0.5793) ya da erken (<1 yıl) ve geç rekürrans (>3 yıl) (p= 0.9950) arasında bir ilişki bulunmadı. Çok-değişkenli Cox orantılı tehlikeler regresyon analizleri sonucunda da GPC3 mRNA seviyesi ile genel sağkalım arasında bir ilişki bulunmadı. Yüksek GPC3 mRNA seviyesi yüksek serum AFP seviyesi, küçük tümör boyutu ve aktif viral replikasyon ile ilişkili bulundu. GPC3 mRNA seviyesi CLIP evre 0’a göre evre 1’de daha yüksekti, fakat TNM ve BCLC evreleme arasında ilişki yoktu.

Sonuç: Çalışma sonuçları HBV-ilişkili HCC ve yakın tümör içermeyen karaciğer doku ayrımında GPC3 mRNA seviyesinin yüksek spesifite ve sensitivite ile iş görebilecek bir diagnostik biyobelirteç olma potansiyelinin oldukça yüksek, fakat prognostik bir biyobelirteç olabilme potansiyelinin düşük olduğunu önermektedir.

Anahtar Kelimeler

Kaynakça

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Ayrıntılar

Birincil Dil

Türkçe

Konular

Sağlık Kurumları Yönetimi

Bölüm

Araştırma Makalesi

Yazarlar

Sevcan Atay ^*
0000-0001-9297-7246
Türkiye

Yayımlanma Tarihi

13 Haziran 2022

Gönderilme Tarihi

31 Ağustos 2021

Kabul Tarihi

10 Ocak 2021

Yayımlandığı Sayı

Yıl 2022 Cilt: 61 Sayı: 2

DOI

https://doi.org/10.19161/etd.1127225

IZ

https://izlik.org/JA79UN93ME

Kaynak Göster

RIS / Bibtex

Vancouver

1.Sevcan Atay. Hepatit-B virüs ilişkili hepatosellüler karsinomda tümöral glipikan 3 mRNA seviyesinin diagnostik ve prognostik biyobelirteç olabilme potansiyelinin entegratif transkriptomik meta-analiz ve biyoinformatik ile değerlendirilmesi. ETD. 01 Haziran 2022;61(2):249-58. doi:10.19161/etd.1127225