Transcriptional characterization of microenvironment and their prediction role for the prognosis of hepatocellular carcinoma after surgery.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15650-e15650
Author(s):  
Kehe Chen ◽  
Haiming Wei ◽  
Tianqi Liu ◽  
Zhenxiang Chen ◽  
Deng Pan ◽  
...  

e15650 Background: Hepatocellular carcinoma (HCC) is one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with HCC, surgical treatment is a potentially cutative therapy. However, the puzzle in the therapy was the rapid recurrence after surgery. The purpose of this study was to integrate the impact of different immune context present in HCC microenvironment on patients’ prognosis, provide the molecular prediction clue of HCC recurrence. Methods: RNA targeted sequencing was performed on 12 primary tumor specimens from HCC patients. Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The lima package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the recurrence post-resection. Results: 15 DEGs were detected in tissue samples between the two groups (group A: patients who relapsed within one year after surgery; group B: patients who hadn't relapsed beyond two years after surgery). The Antigen processing pathway enrichment may associate with the favorable prognosis (p < 0.05). HLA-A gene expression in group A was lower than that in group B; The gene expression of IL23A, TP63, ALOX15B, BUB1, CXCR2, CCL20, CLEC4C, PTK7, MPO, IL1B, MMP9, GAGE2C, GAGE2A, GAGE2E, DMBT1, FOXM1 in group A was higher than that in group B. Additionally, the combination of 3 genes (TP63, IL23A and BUB1) can distinguish the patients recurrent within 1 year or beyond 2 years post-resection. The joint diagnostic equation is logit (Y = 1) = 0.073 +0.740 *(TP63) + 0.589 * (IL23A)+0.959(BUB1), (Optimal threshold: 0.667, specificity: 1, sensitivity: 0.833). Conclusions: Our results suggest that RNA-seq of immune related genes from FFPE sample can effectively profile the specific landscape of tumor immune microenvironment and predict the survival of HCC. 3 genes’ expression (TP63, IL23A and BUB1) might correlate with recurrence in HCC patients after surgery.

2018 ◽  
Author(s):  
Kun Zhao ◽  
Junxin Lin ◽  
Bingbing Wu ◽  
Guofei Sun ◽  
Chengrui An ◽  
...  

AbstractObjectiveTo identity osteoarthritis(OA) subtypes with gene expression of peripheral blood mononuclear cells.MethodsGene expression data (GSE48556) of Genetics osteoARthritis and Progression (GARP) study was downloaded from Gene Expression Omnibus. Principal component analysis and unsupervised clustering were analyzed to identify subtypes of OA and compare major KEGG pathways and cell type enrichment using GSEA and xCell. Classification of subtypes were explored by the utilization of support vector machine.ResultsUnsupervised clustering identified two distinct OA subtypes: Group A comprised of 60 patients (56.6%) and Group B had 46 patients (43.3%). A classifier including nine genes and CD4+T cell and Regulatory T cell flow cytometry could accurately distinguish patients from each group (area under the curve of 0.99 with gene expression). Group A is typical degenerative OA with glycosaminoglycan biosynthesis and apoptosis. Group B is related to Graft versus host disease and antigen processing and presentation, which indicated OA has a new type of “Antigen processing and presentation” similarly as that of RA.ConclusionOA can be clearly classified into two distinguished subtypes with blood transcriptome, which have important significance on the development of precise OA therapeutics.


2017 ◽  
Vol 8 (2) ◽  
pp. 101
Author(s):  
Manssour Ras'n M. Habbash

Electronic reference tools viz. dictionaries, wikis, explorers, translators etc. tender a great support to the EFL learners in understanding different aspects of the lexical, syntactical, phonological and semantic complexities. In view of the usefulness of online reference tools, it is hypothesized that extensive use of the tools in classrooms expedites the acquisition of the language. In an effort to establish the correlation between the effective use of the tools and the acquisition of English as a foreign language, it is proposed to take up a study that aims at finding out the impact of using Electronic reference tools in EFL classrooms. The study was conducted with two groups of learners of English as a foreign language who completed their yearlong English language course that is mandatory for continuing their bachelors’ course. By using purposive sampling method the participants of the study were selected and were divided into group A and group B based on the levels of success in their acquisition of English required for continuing their bachelor’s courses. The levels of success were determined based on a diagnostic test conducted at the end of their one-year English language program, and graded in light of the Interagency Language Round Table Scale (ILRS). The students who obtained ILRS +3 level and above in the test were included in group A, and the students who obtained below ILRS 3 level are included in group B. The final sample of the students in both the groups were provided with a questionnaire of Likert scale that is followed by face-to-face interviews. By employing mixed method model of research, the correlation between their use of online reference tools and their level of success in learning the language were established. The results show a positive correlation that confirms the use of online and electronic reference tools is an essential learning strategy both within and out of the classroom learning as well as for expediting the learning process. 


2020 ◽  
Vol 2 (1) ◽  
pp. 6-11
Author(s):  
C. Ungureanu ◽  
R. Mirică ◽  
R. Iosifescu ◽  
M. Zamfir ◽  
M. Mardare ◽  
...  

Acute pathology of the cecal appendix - appendicitis, is a condition that does not take into account the pandemic period. The aim of this study is to retrospectively analyze the relationship of care for two groups of patients who underwent appendectomy in COVID-19 period and one year before, same period of time, in emergency hospital service. We performed a retrospective analysis on the patients admitted in our surgery center by comparing two groups for each period analysed: group A, for the period March-May 2019 and group B for the period March-May 2020 (corresponding to COVID-19 pandemic). We compared the groups analysing features that prove the change in age, incidence, grade (severity) of appendicitis, delay of surgery, length of surgery, postoperative complications and hospitalization time. CT scan was made for each patient. In the group B, PCR COVID-19 testing was made (all patients were negative for COVID-19). Our study consisted of 52 patients, group A-32 patients (61.53%) and group B-22 patients (38.47%). The Covid-19 pandemic influenced the incidence of appendicitis and we noted a delayed presentation which led to more complicated appendicitis than same period of the previous year. The impact also was noted on length of surgery, due to use of PPE (personal protective equipment) and also modified anatomy of the region related to inflammation. The severity of appendicitis was higher in the COVID-19 period when compared to 2019 similar period of time. Further research is required to draw more conclusions on this period.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 195-195 ◽  
Author(s):  
Wolfgang Kern ◽  
Claudia Schoch ◽  
Alexander Kohlmann ◽  
Martin Dugas ◽  
Sylvia Merk ◽  
...  

Abstract Genetic aberrations substantially contribute to the pathogenesis of acute myeloid leukemias (AML) and have significant prognostic impact. In most cases with AML and normal karyotypes (AML-NK), however, the respective genetic lesions have not yet been identified and patients are assigned an intermediate and thus largely unknown prognosis. To clarify the genetic background and to improve prognostication in AML-NK we analyzed gene expression profiles in 205 patients with untreated and newly diagnosed AML-NK. Samples were comprehensively characterized by cytomorphology, immunophenotyping, cytogenetics, and molecular genetics. For expression profiling, samples were hybridized to both U133A and U133B microarrays (Affymetrix). To identify genetically defined subgroups we performed an unsupervised principal component analysis (PCA) applying all 34023 probe sets from both arrays that were expressed in at least one of the analyzed samples. While the majority of cases (n=162, 79%; group A) clustered together, a subgroup comprizing 43 (21%) cases was identified (group B) which formed a distinct cluster. The analysis of known genetic markers (length mutations and point mutations of FLT3, partial tandem duplications of MLL, mutations of CEBPA, NRAS, or CKIT) did not reveal differences between groups A and B. Significant differences were found, however, in their phenotypes. There were more cases with monocytic leukemias in group B (84% vs. 20%, p<0.001) and the expression levels of CD4, CD56, CD65, CD15, CD14, CD64, CD11b, CD36, CD135, CD87, and CD116 were higher while those of MPO, CD34, and CD117 were lower (p<0.05 for all). To identify the genetic background of differences, samples from groups A and B were supervised compared. Using the top 100 differentially expressed genes and applying SVM with a 10-fold cross validation approach samples could be classified to groups A and B with an accuracy of 97.6% which was confirmed applying 100 runs of SVM with 2/3 of samples being randomly selected as training set and 1/3 as test set (median accuracy, 97.1%, range, 93.4% to 100%). Ingenuity software was used to identify genetic pathways differentially regulated between both groups. Most strikingly, CD14 was higher expressed (fold-change (fc), 10.6) and WT1 and MYCN were lower expressed (fc, 3.7 and 4.4) in group B. Also higher expressed was HCK (fc, 4.3) encoding a protein-tyrosine kinase which phosphorylates STAT3. Since phosphorylated STAT3 stimulates proliferation this may confer higher chemosensitivity and result in a better prognosis. The lower expression of HCK in group A cases may be due to the higher expression of SPTBN1 (fc, 3.4) which also has been shown to increase the transcription of C-FOS and to possibly reveal antiapoptotic effects. To prove the clinical importance of the newly identified subgroups of AML-NK event-free survival (EFS) and overall survival (OS) were compared. All patients were uniformly treated within the German AMLCG trials. Group B had a significantly better median EFS (13.3 vs. 7.0 months, p=0.0143) which was independent of the impact of age. In addition, there was a trend for a better OS in group B (13.3 vs. 9.5 months, n.s.). In conclusion, the identification of a biologically defined and clinically relevant subgroup of AML-NK has been accomplished by use of gene expression profiling based on differences in regulations of genetic pathways involving proliferation and apoptosis.


Author(s):  
Mohamed E. Abdelsalam ◽  
Tomas M. Appleton Figueira ◽  
Joe Ensor ◽  
Alda L. Tam ◽  
Rony Avritscher ◽  
...  

Objective: The objective of the study was to investigate the consequences of using C-arm cone-beam computed tomography (CBCT) on super-selective catheterization of hepatic artery (HA) branches during chemoembolization of hepatocellular carcinoma. Methods: Two groups of patients were created according to the dates of their treatment sessions. Group A and Group B included patients who had their treatment sessions in 2004 - 2005 and 2008 - 2010, respectively. The sessions performed in 2006 and 2007 were excluded to allow for the adoption and incorporation of CBCT imaging into clinical practice. All chemoembolized HA branches were categorized according to selection order (0-1, 2, or ≥3). Other procedure variables were documented. Results: A total of 58 and 183 sessions were included in Groups A and B, respectively, for 144 patients. C-arm CBCT was used in 2 (3%) sessions and 142 (78%) sessions in groups A and B, respectively. The average number of vessels treated was significantly higher in group B (1.8) compared to group A (1.3) (P < .0001). A shift to an increased selection order in group B (0-1, 44 [24%]; 2, 85 [46%]; ≥3, 54 [30%]) was more significant (P = .0004) than that in group A (0-1, 32 [55%]; 2, 18 [31%]; ≥3, 8 [14%]). The average duration of the procedure was significantly longer in group B (P = .0002). Conclusions: Using C-arm CBCT during chemoembolization has a positive impact on increasing the number and order of HA selected and chemoembolized. This comes at the expense of an increase in the duration of the procedure.


2008 ◽  
Vol 14 (6) ◽  
pp. 786-792 ◽  
Author(s):  
B Audoin ◽  
F Reuter ◽  
MVA Duong ◽  
I Malikova ◽  
S Confort-Gouny ◽  
...  

Functional magnetic resonance imaging (FMRI) studies have established that patients with multiple sclerosis show stronger activation in the lateral prefrontal cortices (LPFC) than healthy control subjects during effortful cognitive tasks. The aim of the present study was to assess the impact of these activation changes on cognitive performances. In addition to 19 controls, who were tested at a single time-point to define a standard pattern of fMRI activation during the performance of the Paced Auditory Serial Addition Task (PASAT), 13 patients with clinically isolated syndrome underwent a longitudinal fMRI examination while performing the PASAT at the beginning of the study (M0) and one year later (M12). Relative to the M0 scores, PASAT performances improved in eight patients (group A) and either decreased ( n = 4) or remained unchanged ( n = 1) (group B) in five patients at M12. Random effect analyses (SPM2; Wellcome Institute, London, England) were performed to compare intra-group time-related effects on brain activation (paired t-test between M0 and M12), and inter-group differences were also compared between the two groups of patients (analysis of covariance with PASAT performances as the covariate). Relative to group B, group A showed larger increase in activation between M0 and M12 in the right LPFC. In the whole group of patients, interaction analyses showed that the differences in the PASAT scores between M0 and M12 were correlated with the differences in activation observed in the right LPFC. This longitudinal study shows that in patients with early multiple sclerosis, the increased levels of activation in the right LPFC was associated with improved individual working memory and processing speed performances.


2021 ◽  
Vol 5 ◽  
pp. 9
Author(s):  
Mohamed E. Abdelsalam ◽  
Tomas M. Appleton Figueira ◽  
Joe Ensor ◽  
Alda L. Tam ◽  
Rony Avritscher ◽  
...  

Objectives: The objectives of the study were to evaluate the use of C-arm cone-beam computed tomography (CBCT) for tumor targeting for transarterial chemoembolization (TACE) and its impact on overall survival (OS) in hepatocellular carcinoma patients. Material and Methods: Two groups were retrospectively evaluated according to the date of the first TACE session before and after C-arm CBCT installation in late 2005 (group A [n = 34], 2004–2005; group B [n = 104], 2008+). The years 2006 and 2007 were excluded to allow for the incorporation of this new imaging technology into clinical practice. The vessel selection order was recorded for all TACE sessions. Univariate and multivariate analyses were performed to assess the impact on and predictors of survival. Results: The average TACE selection order for each patient was significantly higher in group B than in group A (P < 0.0001). The median OS was significantly longer in group B (29.34 months) than in group A (19.65 months; P = 0.0088), and the difference in duration was most pronounced in patients with tumor burdens < 25% (n = 93; P = 0.0075), in whom the 3-year survival rate was 56.1% in group B and 15.3% in group A. In these 93 patients, the OS was significant longer (P = 0.018) for high (41.07 months) versus low (19.65 months) vessel selection order across both groups. In multivariate analyses, both the period in which TACE was performed (P = 0.022) and the use of C-arm CBCT (P = 0.0075) were significant predictors of improved OS. Conclusion: Use of advanced C-arm CBCT during TACE enhances the operating physician’s ability to deliver targeted, effective therapy for hepatocellular carcinoma, an aggressive approach that favorably impacts survival.


VASA ◽  
2015 ◽  
Vol 44 (3) ◽  
pp. 0220-0228 ◽  
Author(s):  
Marion Vircoulon ◽  
Carine Boulon ◽  
Ileana Desormais ◽  
Philippe Lacroix ◽  
Victor Aboyans ◽  
...  

Background: We compared one-year amputation and survival rates in patients fulfilling 1991 European consensus critical limb ischaemia (CLI) definition to those clas, sified as CLI by TASC II but not European consensus (EC) definition. Patients and methods: Patients were selected from the COPART cohort of hospitalized patients with peripheral occlusive arterial disease suffering from lower extremity rest pain or ulcer and who completed one-year follow-up. Ankle and toe systolic pressures and transcutaneous oxygen pressure were measured. The patients were classified into two groups: those who could benefit from revascularization and those who could not (medical group). Within these groups, patients were separated into those who had CLI according to the European consensus definition (EC + TASC II: group A if revascularization, group C if medical treatment) and those who had no CLI by the European definition but who had CLI according to the TASC II definition (TASC: group B if revascularization and D if medical treatment). Results: 471 patients were included in the study (236 in the surgical group, 235 in the medical group). There was no difference according to the CLI definition for survival or cardiovascular event-free survival. However, major amputations were more frequent in group A than in group B (25 vs 12 %, p = 0.046) and in group C than in group D (38 vs 20 %, p = 0.004). Conclusions: Major amputation is twice as frequent in patients with CLI according to the historical European consensus definition than in those classified to the TASC II definition but not the EC. Caution is required when comparing results of recent series to historical controls. The TASC II definition of CLI is too wide to compare patients from clinical trials so we suggest separating these patients into two different stages: permanent (TASC II but not EC definition) and critical ischaemia (TASC II and EC definition).


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Xiao-yu Liu ◽  
Hai-feng Shi ◽  
Jie Zheng ◽  
Ku-lin Li ◽  
Xiao-xi Zhao ◽  
...  

Objective. The objective of this study was to investigate the impact of left atrial (LA) size for the ablation of atrial fibrillation (AF) using remote magnetic navigation (RMN). Methods. A total of 165 patients with AF who underwent catheter ablation using RMN were included. The patients were divided into two groups based on LA diameter. Eighty-three patients had small LA (diameter <40 mm; Group A), and 82 patients had a large LA (diameter ≥40 mm; Group B). Results. During mapping and ablation, X-ray time (37.0 (99.0) s vs. 12 (30.1) s, P<0.001) and X-ray dose (1.4 (2.7) gy·cm2 vs. 0.7 (2.1) gy·cm2, P=0.013) were significantly higher in Group A. No serious complications occurred in any of the patients. There was no statistical difference in the rate of first anatomical attempt of pulmonary vein isolation between the two groups (71.1% vs. 57.3%, P=0.065). However, compared with Group B, the rate of sinus rhythm was higher (77.1% vs. 58.5%, P<0.001) during the follow-up period. More patients in Group A required a sheath adjustment (47/83 vs. 21/82, P<0.001), presumably due to less magnets positioned outside of the sheath. In vitro experiments with the RMN catheter demonstrated that only one magnet exposed created the sheath affects which influenced the flexibility of the catheter. Conclusions. AF ablation using RMN is safe and effective in both small and large LA patients. Patients with small LA may pose a greater difficulty when using RMN which may be attributed to the fewer magnets beyond the sheath. As a result, the exposure of radiation was increased. This study found that having at least two magnets of the catheter positioned outside of the sheath can ensure an appropriate flexibility of the catheter.


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