Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection

Iizuka, Norio; Oka, M.; Yamada-Okabe, Hisafumi; Nishida, Minekatsu; Maeda, Yoshitaka; Mori, Naohide; Takao, Tetsuya; Tamesa, Takao; Tangoku, Akira; Tabuchi, Hisahiro; Hamada, Kenji; Nakayama, Hironobu; Ishitsuka, Hideo; Miyamoto, Takanobu; Hirabayashi, Akira; Uchimura, Shunji; Hamamoto, Yoshihiko

doi:10.1016/s0140-6736(03)12775-4

Cited by 463 publications

(374 citation statements)

References 22 publications

Supporting

Mentioning

363

Contrasting

Unclassified

Order By: Relevance

“…As expected, prediction models based on gene expression profiles successfully discriminate HCC from non-tumor livers with expected high accuracy (Kim et al, 2004;Neo et al, 2004;Nam et al, 2005). Many studies have identified differentially expressed gene sets in HCC that differ according to etiological factors (Okabe et al, 2001), mutations of tumor suppressor genes (Chen et al, 2002), rate of recurrence (Iizuka et al, 2003), intrahepatic metastasis (Ye et al, 2003) and different stages (Nam et al, 2005). The results from these studies demonstrate that genomic-scale gene expression profiles recapitulate the well-known morphological distinctions of the tissues and suggest that the differences in gene expression patterns might be biologically relevant.…”

Section: Gene Expression Profiling Of Hccsupporting

confidence: 53%

Comparative and integrative functional genomics of HCC

2006

View full text Add to dashboard Cite

Global gene expression profiling of hepatocellular carcinoma (HCC) is a promising new technology that has already refined the diagnosis and prognostic predictions of HCC patients. This has been accomplished by identifying genes whose expression pattern is associated with clinicopathological features of HCC tumors. Molecular characterization of HCC from gene expression profiling studies will undoubtedly improve the prediction of treatment responses, selection of treatments for specific molecular subtypes of HCC and ultimately the clinical outcome of HCC patients. The research focus is now shifting toward the identification of genetic determinants that are components of the specific regulatory pathways altered in cancers, and that may constitute novel therapeutic targets. Here we review the recent advances in gene expression profiling of HCC and discuss the future strategies for analysing large and complicated data sets from microarray studies and how to integrate these with diverse genomic data.

show abstract

Section: Gene Expression Profiling Of Hccsupporting

confidence: 53%

Comparative and integrative functional genomics of HCC

2006

View full text Add to dashboard Cite

show abstract

“…In contrast, our univariate analysis showed increased levels of cfDNA in HCC patients with early IHR. Most early IHRs can be attributed to intrahepatic metastasis of cancer cells and are detected in 30 -50% of patients within 1 or 2 years after surgery, limiting the potential for surgical cure of HCC (Tung-Ping Poon et al, 2000;Iizuka et al, 2003;Llovet et al, 2003;Matoba et al, 2005;Portolani et al, 2006). Thus, the increased levels of serum cfDNA are related to the high metastatic potential, but not to the appearance of de novo tumour, of this type HCC.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, the remaining 87 patients were subjected to the following study. Patients were followed up as described previously (median follow-up time: 39 months) (Iizuka et al, 2003;Matoba et al, 2005). In brief, all 87 patients were followed up at least once every 3 months postoperatively by routine X-ray, ultrasonography (US), computed tomography, or magnetic resonance imaging, levels of serum a-fetoprotein and protein induced by vitamin K absence II (PIVKA-II) were also measured.…”

Section: Patients and Samplesmentioning

confidence: 99%

“…Particularly in Europe and North America, the incidences of HCC have increased markedly in the last decade and will increase further in the upcoming two decades due to hepatitis C virus (HCV) infection (Deuffic et al, 1998;El Serag, 2004). Despite much effort in HCC research, the prognosis of HCC remains poor because of both a high frequency of intrahepatic recurrence (IHR; Iizuka et al, 2003Iizuka et al, , 2004Llovet et al, 2003) and high mortality of associated with extrahepatic recurrence (EHR) in distant organs (Itoh et al, 2002;Yang et al, 2007). Therefore, new non-invasive prognostic markers are urgently needed to improve the prognosis of HCC, especially of HCV-related HCC.…”

mentioning

confidence: 99%

“…Some recent molecular profiling studies (Iizuka et al, 2003(Iizuka et al, , 2004Kurokawa et al, 2004) raised the possibility of accurately predicting early IHR in a cohort of patients with HCC, most of which were HCV-related HCCs. Predictive systems that are developed will enable to accurately detect patients at high risk for early IHR, but there might be many problems to solve before these markers can be applied to daily clinical practice (Iizuka et al, 2004).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

et al. 2007

View full text Add to dashboard Cite

In a previous study, we showed that levels of cell-free DNA (cfDNA) were significantly higher in sera of patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) than in sera of non-HCC patients with HCV. To confirm this finding, we analysed serum cfDNA levels in a cohort of 96 patients with HCV-related HCC and in 100 HCV carriers without known HCC. Again we found that serum cfDNA levels were significantly higher in HCC patients than in HCV carriers (115.9 ± 98.3 vs 34.4 ± 40.4 ng ml À1 (mean ± s.d.), Po0.0001). Of 87 eligible patients who underwent curative hepatectomy, those with a high cfDNA level had a significantly shorter overall survival (OS) time than those in whom the cfDNA level was not high. Cox proportional hazards model showed the cfDNA level to be an independent prognostic factor for OS and cancer recurrence in distant organs. Our results suggest that the serum cfDNA level reflects the metastatic potential of HCV-related HCC and that it can be a useful predictive biomarker for distant metastasis after curative surgery.

show abstract

Liver regeneration accelerates hepatitis B virus‐related tumorigenesis of hepatocellular carcinoma

et al. 2018

View full text Add to dashboard Cite

Although partial hepatectomy (PH) to remove tumors provides a potential cure of hepatocellular carcinoma (HCC), long‐term survival of hepatitis B virus (HBV)‐related HCC patients after PH remains a big challenge. Early recurrence within 2 years post‐PH is associated with the dissemination of primary HCC. However, late recurrence after 2 years post‐PH is supposed due to the de novo or a secondary tumor. Since PH initiates liver regeneration (LR), we hypothesize that LR may accelerate tumorigenesis through activation of pre‐existing precancerous lesions in the remaining liver. In this study, we explored the potential role of several LR‐related factors in the de novo recurrence in a HBV X protein (HBx) transgenic mouse model receiving PH to mimic human HCC development. Following PH, we observed that tumor development was significantly accelerated from 16.9 to 10.4 months in HBx transgenic mice. The expression of suppressor of cytokine signaling (SOCS) family proteins was remarkably suppressed in livers of HBx transgenic relative to non‐transgenic mice from early to late stages after PH as compared with non‐PH mice. The expression of transforming growth factor‐β (TGF‐β)/Smad pathway, hepatocyte growth factor (HGF), Myc, signal transducer and activator of transcription 3 (STAT3), and β‐Catenin also showed a significant difference between livers of HBx transgenic and non‐transgenic mice at variable time points after PH in comparison with non‐PH mice. Taken together, our results provide an explanation for the high de novo recurrence of HBV‐related HCC after PH, probably through induction of the sequential changes of LR‐related SOCS family proteins, growth factors, and transcription factors, which may promote growth on the precancerous remnant liver.

show abstract

Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection

Cited by 463 publications

References 22 publications

Comparative and integrative functional genomics of HCC

Comparative and integrative functional genomics of HCC

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

Liver regeneration accelerates hepatitis B virus‐related tumorigenesis of hepatocellular carcinoma

Contact Info

Product

Resources

About