Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the ...proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak’s score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression.
The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic ...parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model.
Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction.
HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis.
When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM: To determine the clinical, radiographic and laboratory characterisUcs, diagnostic methods, and therapeutic vadables in immunocompetent patients with tuberculosis (TB) of the pancreas and ...peripancreatic lymph nodes.METHODS: The records of 16 patients (6 male, 10 female;mean age 37 years, range 18-56years) with tuberculosis of the pancreas and peripancreatic lymph nodes from 1983 to 2001 in the Southwest Hospital were analyzed retrospectively.In addition, 58 similar cases published in Chinese literature were reviewed and summarized. We reviewed the clinical,radiographic and laboratory findings, diagnostic methods,therapeultic approaches, and outcome in the patients. Criteria for the diagnosis of pancreatic tuberculosis were the presence of granuloma in histological sections or the presence of Alycobacterium tuberculosis DNA by polymerase chainreaction (PCR).RESULTS: Predominant symptoms consisted of abdominal nodule and pain (75 %), anorexia/weight loss (69 %),malaise/weakness (64 %), fever and night sweats (50 %),back pain (38 %) and jaundice (31%). Swelling of thehead of the pancreas with heterogeneous attenuation echo was detected with ultrasound in 75 % (12/16). CT scan showed pancreatic mass with heterogeneous hypodensity focus in all patients, with calcification in 56 % (9/16) patients, and peripancreatic nodules in 38 % (6/16) patients. Anemia and lymphocytopenia were seen in 50 %(8/16) patients, and pancytopenia occurred in 13 % (2/16) patients. Hypertransaminasemia, elevated alkaline phosphatase (AP) and GGT were seen in 56 % (9/16)patients. The erythrocyte sedimentation rate (ESR) was elevated in 69 % (11/16) cases. Granulomas were found in 75 % (12/16) cases, and in 38 % (6/16) cases caseous necrosis tissue was found. Laparotomy was performed in 75 % (12/16) cases, and ultrasound-guided fine needle aspiration (FNA) was done in 63 % (10 of 16). The most commonly used combinations of medications were isoniazid/rifampin/streptomycin (63 %, n=10) and isoniazid/rifampin pyrazinamide/streptomycin or ethambutol(38 %, n=6). The duration of treatment lasted for half orone year and treatment was successful in all cases. The characteristics of 58 cases from Chinese literature were also summarized.CONCLUSION: Tuberculosis of the pancreas and peripancreatic lymph nodes should be considered as a diagnostic possibility in patients presenting with a pancreatic mass, and diagnosis without laparotomy is possible if only doctors are aware of its clinical features and investigate it with appropriate modalities. Pancreatic tuberculosis can b eeffectively cured by antituberculous drugs.
Background
Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Previously, we reported that cadherin-17 (CDH17) and its related CDH17/β-catenin axis may be responsible ...for inducing HCC in a subset of patients exhibiting CDH17 over-expression. Here we aimed at obtaining a better understanding of the CDH17-related HCC biology and to obtain further indications for the design of targeted therapies in CDH17 over-expressing HCC patients.
Results
We found that SPINK1 acts as a downstream effector of the CDH17/β-catenin axis in HCC. In addition, we found that SPINK1 expression exhibited a positive correlation with CDH17 expression in human HCCs and was over-expressed in up to 70% of the tumors. We identified SPINK1 as a downstream effector of the CDH17/β-catenin axis using a spectrum of in vitro assays, including gene expression modulation and inhibitor assays, bioinformatics analyses and luciferase reporter assays. These in vitro results were validated in primary human HCCs, including the observation that alteration in β-catenin expression (a core component of the CDH17/β-catenin axis) in tumors affects SPINK1 serum levels in HCC patients. Similar to CDH17, SPINK1 expression in HCC cells was found to be associated with specific tumor-related properties via activating the c-Raf/MEK/ERK pathway.
Conclusions
Our current data substantiate our knowledge on the role of CDH17 in the biology of HCC and suggest that components of the CDH17/β-catenin axis may serve as therapeutic targets in CDH17 over-expressing HCC patients.
To evaluate morphologic characteristics and cell viability of radiofrequency ablation zones in porcine liver.
Approval of the study protocol was obtained from the Ethics Committee on Use of Live ...Animals for Teaching and Research at University of Hong Kong. Internally cooled electrodes were used to produce 120 ablated zones ex vivo and 60 ablated zones in vivo with single electrodes (1-, 2-, and 3-cm exposed lengths) or clustered electrodes (1.0-, 2.0-, and 2.5-cm exposed lengths) at 4, 8, 12, and 16 minutes of ablation (ex vivo) and 8 and 12 minutes of ablation (in vivo). Morphologic measurements of each ablated zone were performed. Cell viability in each ablated zone was assessed qualitatively with histochemical staining and quantitatively with measurement of intracellular adenosine 5'-triphosphate (ATP) concentration.
Exposed length of electrode (coefficient = 0.79, standard error = 0.04, P < .001), duration of ablation (coefficient = 0.14, standard error = 0.01, P < .001), and clustered electrode design (coefficient = 1.21, standard error = 0.05, P < .001) were independent factors that affected minimal transverse diameter and volume of ablated zone in ex vivo study. Similar morphologic characteristics existed among ablated zones in in vivo study. Mean distance of ablation beyond the electrode tip remained constant (ex vivo, 1.0 cm +/- 0.08 standard deviation; in vivo, 0.5 cm +/- 0.05) regardless of different ablation conditions. Histochemical staining revealed no viable hepatocytes from center to margins of white zone in each ablated area. Mean intracellular ATP concentration in margins of white zone (9.5 x 10(-12) mol/microg DNA +/- 1.43) was lower than that in red zone (4088 x 10(-12) mol/microg DNA +/- 65.97, P < .001) and in adjacent normal liver (4528 x 10(-12) mol/microg DNA +/- 52.74, P < .001).
Distance of ablation beyond the tip of the electrode remained constant (ex vivo, 1.0 cm; in vivo, 0.5 cm) with different conditions of ablation. Complete and uniform cellular destruction was achieved in the white zone of ablated area.
Background: Breast conservation therapy is an established procedure for treating invasive breast cancer. However, little has been reported in the literature about its applicability in the Chinese. ...This study was done to find out the local recurrence and mortality rates of such therapy among Hong Kong Chinese women. In addition, the prognostic factors were also examined.
Methods: A retrospective study reviewing clinical records of breast cancer patients treated between February 1986 and September 1994 was undertaken.
Results: Sixty‐four female patients were identified. The follow‐up period ranged from 8 to 90 months with a median of 46 months. The median age at diagnosis was 51 years and 50% of patients were postmenopausal. The median tumour size was 2.5 cm and 20 patients had involved axillary lymph nodes. Ten (16%) patients developed ipsilateral breast tumour recurrence and seven underwent salvage mastectomy. Lymphovascular permeation by tumour cells was the only factor significantly associated with recurrence. Five (8%) eventually died; the 5‐year disease‐free and overall survival rates were 42% and 83%, respectively. Ipsilateral breast tumour recurrence correlated with a higher mortality rate whereas adjuvant treatment with either chemotherapy or tamoxifen improved the outcome.
Conclusions: Breast conservation therapy is an acceptable alternative in the treatment of breast cancer in Chinese patients.
We present a case of a 53-year-old woman with abdominal discomfort for 6 months. The liver was enlarged. Contrast CT scan of the abdomen revealed a 10 cm hypervascular tumour at the right lobe of the ...liver. Right hepatectomy with complete excision of the tumour was achieved. Histological and immunohistochemical findings were consistent with perivascular epithelioid cell tumour. She is regularly followed up with contrast CT assessment. There is no tumour recurrence 12 months after the operation.
Abstract
Elucidating the molecular basis of Hepatocellular Carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. Somatically acquired structural ...variations (SVs) can lead to oncogenic gene fusions and gene expression deregulation in tumors. Although recent studies have delineated HCC genomic alterations including copy number variations, somatic mutations and HBV integrations, the landscape of SVs remains poorly characterized in HCC. We have predicted 4,314 SVs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. TP53 and RB1 alterations appear to cause increased levels of genomic arrangement and chromosomal instability. Albumin (ALB) was found to be the most significantly affected by SVs and harbor genomic alterations including deactivating mutations and deletions in 10.2% of cohort. Integrative analysis revealed a causal link between genomic rearrangements and copy number variations, such as focal amplifications of the CCND1/FGF19 loci, and distinctive patterns of copy number variation flanking SV breakpoints. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3′ genes in tumors.
Citation Format: Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing Kin Sun, Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul Rejto, Mao Mao, Zhengyan Kan. Decoding complex patterns of structural variations in hepatocellular carcinoma. abstract. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-231. doi:10.1158/1538-7445.AM2013-LB-231
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