Robust transcriptional tumor signatures applicable to both formalin-fixed paraffin-embedded and fresh-frozen samples
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Formalin-fixed paraffin-embedded (FFPE) samples represent a valuable resource for clinical researches.However, FFPE samples are usually considered an unreliable source for gene expression analysis due to the partial RNA degradation.In this study, through comparing gene expression profiles between FFPE samples and paired fresh-frozen (FF) samples for three cancer types, we firstly showed that expression measurements of thousands of genes had at least two-fold change in FFPE samples compared with paired FF samples.Therefore, for a transcriptional signature based on risk scores summarized from the expression levels of the signature genes, the risk score thresholds trained from FFPE (or FF) samples could not be applied to FF (or FFPE) samples.On the other hand, we found that more than 90% of the relative expression orderings (REOs) of gene pairs in the FF samples were maintained in their paired FFPE samples and largely unaffected by the storage time.The result suggested that the REOs of gene pairs were highly robust against partial RNA degradation in FFPE samples.Finally, as a case study, we developed a REOs-based signature to distinguish liver cirrhosis from hepatocellular carcinoma (HCC) using FFPE samples.The signature was validated in four datasets of FFPE samples and eight datasets of FF samples.In conclusion, the valuable FFPE samples can be fully exploited to identify REOs-based diagnostic and prognostic signatures which could be robustly applicable to both FF samples and FFPE samples with degraded RNA.Objective: To screen the differential expression genes of Kanglaite Injection in treating cancer cachexia. Methods: mRNA was extracted from the blood cells of T739 animal model of C.C., hybridizated respectively on 20S gene chip. Analysis discuss on differential expression genes was carried out. Results: 5 differential expression genes were obtained. Among these genes, 4 genes were up-regulated and 1 gene was down-regulated. Most of these genes were related with immunity and metabolism of tumor. Conclusion: cDNA microarray for analysis of gene expression patterns is a powerful method to identify associated genes of Kanglaite.
Cancer Cachexia
Gene chip analysis
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ABSTRACT It is not understood what evolutionary factors drive some genes to be expressed at a higher level than others. Here, we hypothesized that a gene’s function plays an important role in setting expression level. First, we established that each S. cerevisiae gene is maintained at a specific expression level by analyzing RNA-seq data from multiple studies. Next, we found that mRNA and protein levels were maintained for the orthologous genes in S. pombe , showing that gene function, conserved in orthologs, is important in setting expression level. To further explore the role of gene function in setting expression level, we analyzed mRNA and protein levels of S. cerevisiae genes within gene ontology (GO) categories. The GO framework systematically defines gene function based on experimental evidence. We found that several GO categories contain genes with statistically significant expression extremes; for example, genes involved in translation or energy production are highly expressed while genes involved in chromosomal activities, such as replication and transcription, are weakly expressed. Finally, we were able to predict expression levels using GO information alone. We created and optimized a linear equation that predicted a gene’s expression based on the gene’s membership in 161 GO categories. The greater number of GO categories with which a gene is associated, the more accurately expression could be predicted. Taken together, our analysis systematically demonstrates that gene function is an important determinant of expression level.
Pair-rule gene
Transcription
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Foreword. Preface. 1. The background to hepatocellular carcinoma and the liver. 2. Premalignant lesions of hepatocellular carcinoma. 3. Pathomorphologic characteristics of early-stage small hepatocellular carcinoma. 4. Morphologic evolution of hepatocellular carcinoma: from early to advanced. 5. Angioarchitecture of hepatocellular carcinoma. 6. Advanced hepatocellular carcinoma. 7. Multicentric occurrence of hepatocellular carcinoma. 8. Combined hepatocellular carcinoma and cholangiocarcinoma. 9. Nodular lesions mimicking hepatocellular carcinoma. 10. Biopsy diagnosis of tumorous lesions of the liver. 11. Chemoprevention of hepatocellular carcinoma. Index
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Evolutionary rates provide important information about the pattern and mechanism of evolution. Although the rate of gene sequence evolution has been well studied, the rate of gene expression evolution is poorly understood. In particular, it is unclear whether the gene expression level and tissue specificity influence the divergence of expression profiles between orthologous genes. Here we address this question using a microarray data set comprising the expression signals of 10,607 pairs of orthologous human and mouse genes from over 60 tissues per species. We show that the level of gene expression and the degree of tissue specificity are generally conserved between the human and mouse orthologs. The rate of gene expression profile change during evolution is negatively correlated with the level of gene expression, measured by either the average or the highest level among all tissues examined. This is analogous to the observation that the rate of gene (or protein) sequence evolution is negatively correlated with the gene expression level. The impacts of the degree of tissue specificity on the evolutionary rate of gene sequence and that of expression profile, however, are opposite. Highly tissue-specific genes tend to evolve rapidly at the gene sequence level but slowly at the expression profile level. Thus, different forces and selective constraints must underlie the evolution of gene sequence and that of gene expression.
Molecular evolution
Sequence (biology)
Rate of evolution
Divergence (linguistics)
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Hepatocellular carcinoma is the most common malignancy among males and the 7th among female patients in the Kingdom of Saudi Arabia. This is due to the endemicity of hepatitis B and hepatitis C. Spontaneous rupture of hepatocellular carcinoma is rare. We report 4 cases of spontaneous rupture of hepatocellular carcinoma. Initial control of bleeding was achieved surgically in 3 patients and by embolization in the 4th patient. All patients had very good hepatic reserve as reflected by Child-Pugh scoring (A & B). We found that the incidence of ruptured hepatocellular carcinoma among 85 patients was 4.7%. The prognosis of this subgroup of patients is poor as reflected by the low median survival ranging from 6-16 weeks.
Hepatitis C
Hepatitis B
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To study the genes differentially expressed in the liver of Kkay diabetic and normal mice by genomic-scale gene expression analysis.cDNA microarray chips containing 8,192 cDNAs were used to explore the gene expression pattern of Kkay mouse liver.One hundred and fifty-four genes were screened out, including 68 complete cDNAs and expressed sequence tags, and among them 40 genes were up-regulated and 114 genes were down-regulated respectively.Most of the gene expression analysis results were consistent with previous study, and the gene expression pattern of Kkay mouse based on cDNA microarray could be used for high-throughout screening out the genes associated with type 2 diabetes.
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The problem and approaches to the treatment of hepatocellular carcinoma as seen in Japan are reported. Current Japanese methods for the detection of hepatocellular carcinoma and the methods used to treat hepatocellular carcinoma are described. Included in the latter discussion is a description of the untoward effects of each treatment. Finally an alogorithm for the treatment of hepatocellular carcinoma is presented based upon the Japanese experience.
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Objective To analyze the differential gene expression profiling of liver in rats subjected to hemorrhagic shock(HS) and sham hemorrhage shock(SHAM) by gene chip technology, thus to evaluate the possible molecular pathogenesis of HS. Method 20 male Wistar rats were randomly divided into a SHAM group and a HS group, with 10 rats in each group. Hepatic gene expression profiles were detected by oligonucleotide microarrays of 5705 mouse genes in two groups for three times. Genes with ratio(R) > 2 were identified as up-regulated and R < 0.5 were identified as down-regulated. Biological function of differentially expressed genes was analyzed and 9 genes were selected to undergo semi-quantitative RT-PCR. Results Among the total 5705 probes detected,86 genes showed differential expression in HS group comparison with SHAM group. The expression levels of 72 genes were up-regulated while those of 14 genes were down-regulated significantly. Differentially expressed genes were classified according to their biological function: transport genes, transcription regulator genes, signaling genes, response to stress genes, metabolic genes, development genes and cell adhesion genes. Conclusions cDNA microarray is an efficient and high-throughout method to survey gene expression profiles in HS.The variation of those gene expressions might be a potential pathogenic mechanism for HS that may offer a novel target for further study of therapeutic strategies of HS.
Key words:
Hemorrhagic shock; DNA chip; Gene expression; liver
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Direct acting antivirals stabilize or improve liver function in the majority of patients with hepatitis C virus cirrhosis. Hepatic decompensation is the main driver of death of patients with early, successfully treated hepatocellular carcinoma superimposed to cirrhosis. Treatment with direct acting antivirals could improve the prognosis of these subjects, independently from the subsequent course of hepatocellular carcinoma, if the efficacy in obtaining viral clearance is as high as in patients without a history of hepatocellular carcinoma, and if the risk of hepatocellular carcinoma recurrence is unaffected. When dealing with hepatocellular carcinoma patients, direct acting antivirals can be indicated in two different settings: (a) subjects in which hepatocellular carcinoma has been already successfully treated ("cured" hepatocellular carcinoma), or (b) subjects whose hepatocellular carcinoma is still untreated or untreatable ("active" hepatocellular carcinoma). Although there are abundant data on "cured" hepatocellular carcinoma, evidence supporting treatment decisions in patients with "active" hepatocellular carcinoma is at best scarce and controversial, since these patients as well as patients with hepatocellular carcinoma listed for liver transplantation are usually excluded from treatment.
Hepatitis virus
Liver Cancer
Hepatocellular cancer
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The aim of this study was to determine the characteristics of hepatocellular carcinoma at a major health center in southern Turkey. Computed tomography was compared to the combination of ultrasonography and serum alpha-fetoprotein determination in the diagnosis of hepatocellular carcinoma.Of 226 patients with liver cirrhosis, 35 were diagnosed with hepatocellular carcinoma on first admission or during follow-up in the period between 1999 and 2002. The features investigated were, age at time of hepatocellular carcinoma diagnosis, etiology of cirrhosis, severity of cirrhosis at presentation, tumor pattern, stage of hepatocellular carcinoma, serum alpha-fetoprotein level, and dynamic computed tomography findings. Results were compared to previous findings in Turkey and elsewhere.In the hepatocellular carcinoma patients, the male:female ratio was 4:1 and the mean age at presentation was 61 years. Chronic hepatitis B virus infection (65.7%) and chronic hepatitis C virus infection (28.6%) were the most frequently identified risk factors for hepatocellular carcinoma. Forty percent of the patients had Child-Pugh A cirrhosis when they were diagnosed with hepatocellular carcinoma. Sixty-seven percent of patients had fewer than three hepatocellular carcinoma nodules in the liver at the time of diagnosis. Only three of the hepatocellular carcinoma cases were Okuda stage I. The combination of ultrasonography and serum alpha-fetoprotein >20 ng/ml identified hepatocellular carcinoma in 32 of the 35 total cases.The results indicate that hepatitis B virus infection in patients with cirrhosis is still the leading risk factor for the development of hepatocellular carcinoma. Also, early-stage hepatocellular carcinoma is rarely diagnosed in cirrhosis patients from this region of Turkey. Surveillance with computed tomography for early diagnosis of hepatocellular carcinoma seems not to be mandatory.
Hepatitis B
Hepatitis C
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