Shingo Tsuji

Shingo Tsuji
The University of Tokyo | Todai · Research Center for Advanced Science and Technology

Ph. D.

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142
Publications
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Introduction
Skills and Expertise

Publications

Publications (142)
Article
Background: We aimed to validate our algorithm for resecting Hepatocellular carcinoma (HCC) in the caudate lobe based on tumor location, tumor size, and indocyanine green clearance rate. Methods: Patients who underwent curative resections for solitary HCC in the caudate lobe were included. The surgical outcomes of patients with HCC in the caudat...
Article
Full-text available
Background Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel the...
Article
Background Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance e...
Preprint
Full-text available
Background Serotonin contributes to liver cancer progression; however, it also plays a pivotal role in liver regeneration after partial resection. This study aims to elucidate whether high serum serotonin is a prognostic factor for patients with hepatocellular carcinoma (HCC).Methods We measured the pre-operation serum serotonin level of patients w...
Article
The presence of esophageal varices (EV) is a phenotype of portal hypertension, and the indications of liver resection for hepatocellular carcinoma (HCC) in patients with concomitant EV are conflicting. This retrospective study aimed to elucidate if there is justification for liver resection in patients with EV. The surgical outcomes were compared b...
Article
Multiplicity is one of the characteristics of hepatocellular carcinoma (HCC), and patients with multiple HCC (≤ 3 nodules) are recommended as candidates for liver resection. To confirm the validity of resecting multiple HCC, we compared the surgical outcomes in patients with synchronous and metachronous multiple HCC. Patients who underwent resectio...
Article
A low platelet count, one of parameters of portal hypertension, is clinically a predictor of postoperative mortality, while platelets induce tumor development during growth factor secretion. In this study, we retrospectively investigated whether high platelet count negatively affects the survival of patients with hepatocellular carcinoma (HCC). Pat...
Preprint
Full-text available
(Background) Identification of novel therapeutic targets is a key for successful drug development. However, the cost to experimentally identify therapeutic targets is huge and only ~400 genes are targets for FDA-approved drugs. Therefore, it is inevitable to develop powerful computational tools to identify potential novel therapeutic targets. Becau...
Article
Cancer develops through the accumulation of genetic and epigenetic aberrations. To identify sequential molecular alterations that occur during the development of hepatocellular carcinoma (HCC), we compared 52 early and 108 overt HCC samples by genome sequencing. Gene mutations in the p53/RB1 pathway, WNT pathway, MLL protein family, SWI/SNF complex...
Article
C-reactive protein (CRP)- and albumin (Alb)-based scoring systems are available for predicting the prognosis of patients with diverse forms of gastrointestinal cancer, but their utility for patients with intrahepatic cholangiocarcinoma (ICC) is still unclear. This study aimed to elucidate whether a high CRP/Alb ratio is associated with the surgical...
Article
Aim Repeat resection for intrahepatic recurrent hepatocellular carcinoma (HCC) is effective for the long‐term survival of patients; however, little is known about the surgical outcomes of extrahepatic nodules. The aim of this study is to investigate whether resection can contribute to the survival of patients with extrahepatic recurrent HCC. Metho...
Article
Background Despite curative resection, hepatocellular carcinoma (HCC) has a high probability of recurrence. We validated the potential role of liver resection (LR) for recurrent HCC. Methods Patients with intrahepatic recurrence with up to three lesions were included. We compared survival times of patients undergoing their first LR to those of pat...
Article
Objectives We aimed to assess the diagnostic performance of MR elastography (MRE) in predicting esophageal varices (EVs) in patients with chronic liver disease. Methods We prospectively performed liver (LSM) and spleen stiffness measurements (SSM) using MRE and endoscopic screening for EVs to determine if patients with hepatocellular carcinoma wer...
Article
Practical cancer genome medicine requires large-scale data analysis for many types of biological data such as cancer driver mutations, aberrantly methylated regions, gene expression also biological knowledge from literature. Machine learning algorithms play an important role in bioinformatics of clinical oncology. In this review, we examine the app...
Article
Aim: Although radiofrequency ablation (RFA) is an effective local treatment of hepatocellular carcinoma (HCC), local recurrence is relatively frequent. We aimed to elucidate the validity of salvage liver resection for recurrent HCC after RFA. Methods: Patients who underwent liver resection for recurrent HCC after RFA (LR after RFA) and those who un...
Article
Full-text available
Background Liver stiffness measurement (LSM) has recently become available for assessment of liver fibrosis. We aimed to develop a prediction model for liver fibrosis using clinical variables, including LSM. Methods We performed a prospective study to compare liver fibrosis grade with fibrosis score. LSM was measured using magnetic resonance elasto...
Article
Multiple hepatocellular carcinoma (HCC) is categorized into two types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is quite difficult to determine it correctly even after histological diagnosis. In order to determine multiple HCC as MC or...
Article
Background: Cirrhosis is associated with blood loss during liver resection and postoperative complications. The liver stiffness measurement has recently become available for assessment of liver fibrosis. Methods: This prospective study was performed to predict postoperative outcomes of liver resection. The liver stiffness measurement was measure...
Article
Aim: Diabetes mellitus (DM) is a potential risk factor for hepatocarcinogenesis, especially in patients with hepatitis C virus (HCV) infection. We aimed to elucidate whether DM influences the surgical outcomes of patients with hepatocellular carcinoma (HCC). Methods: Our patients were routinely controlled to keep urinary glucose excretion to les...
Article
307 Background: Multiple hepatocellular carcinoma (HCC) is categorized into 2 types; multicentric carcinogeneis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is difficult to determine it correctly even after histological diagnosis. Methods: In order to classify multiple HCC...
Article
Full-text available
Objective Early diagnosis and treatment of cancer may contribute substantially to complete cure, but it remains unknown whether treatment of early hepatocellular carcinoma can actually result in cure. This study was performed to clarify the cancer risk of the background liver after treating early hepatocellular carcinoma. Methods Early hepatocellu...
Article
Multiple hepatocellular carcinoma (HCC) is categorized into 2 types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is quite difficult to determine it correctly even after histological diagnosis. In order to classify multiple HCC into MC and...
Article
Background: Incidental detection of nonenhancing tumors during imaging studies for patients with classical hepatocellular carcinoma is not unusual. These tumors are considered to have a high potential of malignant transformation. The aim of this study was to clarify the natural history of such tumors. Methods: In 93 patients who underwent liver...
Article
Full-text available
Background: In liver resection, bile leakage remains the most common cause of operative morbidity. In order to predict the risk of this complication on the basis of various factors, we developed a clinical score system to predict the potential risk of bile leakage after liver resection. Methods: We analyzed the postoperative course in 518 patien...
Article
Background Hypovascular tumors associated with hepatocellular carcinoma (HCC) can be diagnosed, but it remains unknown whether such lesions should be treated immediately. This study aimed to clarify the clinical significance of treating hypovascular liver nodules. Methods After diagnosis of hypovascular tumors smaller than 3 cm, 104 patients underw...
Article
Although high-throughput biological technologies have been producing a vast amount of multi-omics data regarding cancer genomics and several disease susceptible genes have been reported, many of these genes are likely to be irrelevant for the cancer process because only one feature of the tumor pathway could be focused on. By identifying ‘CpG core’...
Data
Data S1. Detailed methods. Data S2. Supplementary references. Fig. S1. Kaplan–Meier curves for progression‐free survival and overall survival after anti‐epidermal growth factor receptor treatment in third‐line patients in the unified cohort according to genome‐wide DNA methylation status. Fig. S2. Mutual relations of the cases classified in the...
Conference Paper
The advanced cancer research fields have been producing vast amount of multi-omics data in various cancer types, and the most of the data are publicly available. It is unquestionably important to analyze these data with unbiased and generalized methodology for obtaining the deeper insights into cancer biology. Machine learning algorithms, such as k...
Article
Full-text available
Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (mCRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti-EGFR treatment. Here, We investigated the genome-wide DNA methylation status in metastatic colorectal cancer to identify associations bet...
Conference Paper
Early hepatocellular carcinoma (HCC) is defined as a very well differentiated cancer containing Glisson's triad with stromal invasion of, which originates from chronic liver disease and develops into classical HCC with accumulation of genetic aberrations. To identify sequential genetic alterations in stepwise hepatocarcinogenesis, transcriptome and...
Article
Full-text available
Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy...
Article
High-throughput biological technologies enabled to identify cancer related key molecules and subclasses. However, single experiment could only elucidate one feature of the tumor pathway. In order to identify the clusters and pathways significant for cancer progression, we performed integrated analysis using gene expression and DNA methylation profi...
Article
Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different p...
Article
Background: Only a few papers have focused on the surgical outcomes of patients with hepatocellular carcinoma (HCC) associated with the metabolic syndrome. We compared the outcomes of patients with metabolic HCC with those of patients with non-B, non-C HCC associated with other etiologies. Methods: Metabolic HCC was defined as HCC arising in pat...
Article
Aberrant DNA methylation plays an important role in genesis of colorectal cancer (CRC). Previously, we identified Group-1 and Group-2 methylation markers through genome-wide DNA methylation analysis, and classified CRC and protruded adenoma into three distinct clusters: high-, intermediate-, and low-methylation epigenotypes. High-methylation epigen...
Article
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Early hepatocellular carcinoma (HCC) is histologically diagnosed as the existence of intratumoral portal tracts with stromal invasion. It consists of small hepatocytes with little cellular atypia but with structural atypia. This type of very well-differentiated cancerous tissue...
Article
Full-text available
BACKGROUND: Mutations in the H3F3A gene, which encodes histone H3.3, were recently reported in cases of pediatric glioblastoma. H3F3A K27M mutations occur in gliomas that arise at midline locations, including the pons, thalamus, and spine; moreover, this particular mutation is found mainly in tumors in children and adolescents. In this study, we ai...
Article
Small cell lung cancer (SCLC), approximately 15% of all the lung cancer cases, is a subtype of lung cancer with poor prognosis. Expression profiling analysis of 23 SCLC cases and 42 normal tissues revealed that EZH2 and other PRC2 members were highly expressed in SCLC. ChIP-seq analysis for H3K27me3 in 3 SCLC cell lines, Lu130, H209 and DMS53, show...
Article
Full-text available
Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 no...
Article
IntroductionMutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma. Additionally, H3F3A K27M substitutions occur in gliomas that arise at midline locations (eg, pons, thalamus, spine); moreover, this substitution occurs mainly in tumors in children and adolescents. Here, we sought to determine the association betwe...
Article
Although clinical applications of intraoperative fluorescence imaging of liver cancer using indocyanine green (ICG) have begun, the mechanistic background of ICG accumulation in the cancerous tissues remains unclear. In 170 patients with hepatocellular carcinoma cells (HCC), the liver surfaces and resected specimens were intraoperatively examined b...
Article
Full-text available
Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. Expression array analysis of 23 SCLC cases and 42 normal tissues revealed that EZH2 and other PRC2 members were highly expressed in SCLC. ChIP-seq for H3K27me3 suggested that genes with H3K27me3(+) in SCLC were extended not only to PRC2-target genes in ES cells but also...
Data
Full-text available
Supplementary Information
Article
Early hepatocellular carcinoma (HCC) originates from the hepatocytes of chronic liver disease and develops into classical HCC. To identify sequential genomic changes in multistep hepatocarcinogenesis, we analyzed fusion genes and mutations using next generation sequencer about 40 early and 80 advanced HCCs. First, exome sequence showed that base se...
Article
Background & aims: Early treatment has been recommended for hepatocellular carcinoma (HCC) due to its high cure rate. However, the reported survival benefits of treating early HCC may be affected by lead time. Methods: Early HCC was defined as a well-differentiated cancer containing Glisson's triad (carcinoma in situ). We applied the concept of...
Article
Full-text available
Background In the functional genomics analysis domain, various methodologies are available for interpreting the results produced by high-throughput biological experiments. These methods commonly use a list of genes as an analysis input, and most of them produce a more complicated list of genes or pathways as the results of the analysis. Although th...
Article
In colorectal cancer (CRC) care, treatment decisions depend on efforts to estimate the metastatic potential of tumors. The liver is one of the most common metastatic sites of CRC and prognosis of CRC patients often reflects metastases to distant sites. However, the molecular mechanisms for further development of CRC with metastasis to the liver, lu...
Article
Insulin/insulin-like growth factor-1 (IGF-1) signaling plays an important role in many biological processes. The class IA isoform of phosphoinositide 3-kinase (PI3K) is an important downstream effector of the insulin/IGF-1 signaling pathway. The aim of this study is to examine the effect of persistent activation of PI3K on gene expression and marke...
Article
Stratification of patients for multidrug response is a promising strategy for cancer treatment. Genome-based prediction models have great potential for this purpose because the extent of drug sensitivity may be attributed to the heterogeneity of the underlying genetic characteristics of cancer. However, microarray data is difficult to analyze and i...
Article
Full-text available
Molecular characterisation using gene-expression profiling will undoubtedly improve the prediction of treatment responses, and ultimately, the clinical outcome of cancer patients. To establish the procedures to identify responders to FOLFOX therapy, 83 colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into...
Data
Relation between expression and histone marks (+/−). (A) For epigenetic status of H3K4me3, genes with >4 reads per million reads within a window size of 300 bp were regarded as H3K4me3(+), and genes with <3 reads were as H3K4me3(-). Mean and standard error of expression signal (GeneChip score) were shown. Markedly high expression was confirmed in H...
Data
Decreased enrichment of Ezh2 around TSS of Bmp2. Quantitative ChIP-PCR was performed for ∼100 bp upstream (region 1) and ∼300 bp downstream (region 2) of Bmp2 TSS (See Figure 3A), and shown by relative fold enrichment compared to Actb (Figure 1D). Decreased enrichment of Ezh2 around Bmp2 TSS was shown (*P<0.05). (TIF)
Data
Expression analysis of Ezh2 and Jmjd3. Real-time RT-PCR was performed, and normalized to Ppib, and relative expression levels compared to MEFp2 was shown. Ezh2 expression level was decreased in RasV12-induced senescence, but similar downregulation was observed during three passages without viral infection, or with mock and RasG12 infection. Similar...
Data
The motifs within Smad1 binding regions by DME. To confirm the GADEM result (Figure S9), the motifs were searched for by another software DME2 (http://rulai.cshl.edu/dme/), using ZOOPS model with default parameters except -w (minimum desired motif width) = 10 and -n (number of motifs to produce) = 10. The results were drawn by STAMP, including the...
Data
H3K4me3 and H3K27me3 levels were shown by the maximum number of the mapped Solexa reads per million reads within a window size of 300 bp and 500 bp, respectively, for 2 kb around TSS. Expression levels were shown by GeneChip score. Two Bmp2/Smad1 signal inhibitors, Smad6 and Nog, were included in the nine genes with H3K27me3 gain and H3K4me3 loss....
Data
Location of TSS was regarded as +1. (DOC)
Data
Induction of activated Ras by retrovirus infection. (A) Western blot analysis of Ras protein. Expression of Ras protein with N-terminal FLAG tag was confirmed by western blot analysis using anti-FLAG antibody. (B) Count of senescence-associated β-galactosidase (SA-βgal)-positive cells. MEF cells at passage 2 (MEFp2, open box) rarely showed SA-βgal(...
Data
Distribution of epigenetic marks. (A) Distribution of H3K4me3 and H3K27me3 marks around TSS was shown by the number of mapped Solexa reads per million reads within a window size of 300 bp and 500 bp, respectively. The distribution was similar between MEFp2 and RasV12. The peak of H3K4me3 mark was detected at +247 bp for MEFp2, and at +312 bp for Ra...
Data
Cellular immunofuorescence for RasV12 and Smad6. RasV12 with N-terminal FLAG and Smad6 with N-terminal Myc were detected using anti-FLAG and anti-Myc antibodies. Simultaneous expression of RasV12 and Smad6 proteins in Smad6-introduced RasV12 cells was confirmed (See also Figure 4E). (TIF)
Data
Decreased SA-βgal(+) cells by Smad6 overexpression. Retrovirus of Smad6 cDNA was infected with Mock or RasV12 retrovirus. Smad6-induced RasV12 cells showed decreased number of SA-βgal(+) cells compared to RasV12 cells (black box). Smad6 induction did not affect on Mock cells (horizontally striped box). (TIF)
Data
The motifs within Smad1 binding regions by GADEM. GADEM version1.3 (http://www.niehs.nih.gov/research/resources/software/gadem/index.cfm) was used to search for the motifs with default parameters except -posWt (Weight profile for positions on the sequence) = 1, -pv (P-value cutoff) = 0.00001, -em (Number of EM steps) = 20, and -fullScan = 1. The en...
Data
Parvb in Ras-induced senescence. (A) Real-time RT-PCR showed that Parvb was knocked down by shRNA to 0.05-fold. (B) Parvb-knocked down RasV12 cells showed partially decreased number of SA-βgal(+) cells compared to RasV12 cells, though higher than Mock level. (TIF)
Data
H3K4me3 and H3K27me3 levels were shown by the maximum number of the mapped Solexa reads per million reads within a window size of 300 bp and 500 bp, respectively, for 2 kb around TSS. Expression levels were shown by GeneChip score. Secreted factors Bmp2 and Igfbp3 were shown to be highly upregulated with H3K27me3 loss and H3K4me3 gain. (DOC)
Data
Smad1 target genes without H3K27me3 increase were correlated to upregulation (Figure 7). Among Smad1 target genes upregulated in RasV12 cells, top ranking 30 genes showing >3-fold upregulation were listed. None of these genes showed H3K27me3 increase >0.4. These genes were regarded as selectively upregulated Smad1 target genes, and expected to incl...
Data
Location of TSS was regarded as +1. (DOC)
Data
Schema of experiments. (A) Candidate factors to induce senescence are to be identified from genes upregulated, with loss of repressive epigenetic mark and with gain of active mark. (B) Candidate inhibitors to senescence are to be identified from genes downregulated, with gain of repressive epigenetic mark and with loss of active mark. (TIF)
Data
Smad1 target genes were generally upregulated by Bmp2 stimulation in MEF (Figure 6), but genes with H3K27me3 increase e.g. Smad6 and Atoh8 were repressed in RasV12 cells. Smad1 target genes without H3K27me3 increase were correlated to upregulation (Figure 7 and Table S6). (DOC)
Data
Ppib and PPIA were used for normalization. (DOC)
Data
Supporting Materials and Methods, and references for them, are available in Text S1. (DOC)