scholarly journals Increased RCAS1 Expression Is Associated with Advanced Histopathological Stage and Poor Prognosis in Patients with Gastric Adenocarcinoma

2013 ◽  
Vol 35 ◽  
pp. 213-219 ◽  
Author(s):  
Constantinos Giaginis ◽  
Themistoclis Efkarpidis ◽  
Paraskevi Alexandrou ◽  
Efstratios Patsouris ◽  
Gregory Kouraklis ◽  
...  

Background. The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that has been considered to play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. The present study aimed to evaluate the clinical significance of the RCAS1 expression in gastric adenocarcinoma.Material and Methods. RCAS1 protein expression was assessed immunohistochemically on 54 gastric adenocarcinoma tissue samples and was analyzed in relation to clinicopathological parameters, tumor proliferative capacity, and patients’ survival.Results. Enhanced RCAS1 expression levels were significantly associated with advanced histopathological stage and presence of organ metastasis (P=0.0084andP=0.0327). Gastric cancer patients with elevated RCAS1 expression levels showed significantly shorter survival times compared to those with low RCAS1 expression (log-rank test,P=0.0168). In multivariate analysis, histopathological stage and grade of differentiation as well as the RCAS1 expression were identified as independent prognostic factors (Cox regression analysis,P=0.0204,P=0.0035, andP=0.0081).Conclusions. Our data support the evidence that RCAS1 upregulation may contribute to gastric malignant progression, representing a useful biomarker to predict the biological behaviour and prognosis in gastric neoplasia.

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Vaquero-Yuste ◽  
Ignacio Juarez ◽  
Marta Molina-Alejandre ◽  
Elisa María Molanes-López ◽  
Adrián López-Nares ◽  
...  

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.


2021 ◽  
Vol 22 (24) ◽  
pp. 13283
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Oskan Tasinov ◽  
Desislava P. Ivanova ◽  
George St. Stoyanov ◽  
...  

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients’ plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2−ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression—20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02–2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.


Author(s):  
Luciana Veronez ◽  
Paola Fedatto ◽  
Carolina Corrêa ◽  
Régia Lira ◽  
Mirella Baroni ◽  
...  

Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. Despite extensive efforts, identifying reliable prognostic factors for pediatric patients with ACT remains a challenge. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and prognosis of several types of cancer. However, the role of miRNAs has been poorly explored in pediatric ACT. In this study, we performed miRNA microarray profiling on a cohort of 37 pediatric ACT and nine non-neoplastic adrenal (NNA) samples and evaluated the prognostic significance of abnormally expressed miRNAs using Kaplan-Meier plots, log-rank test and Cox regression analysis. We identified a total of 98 abnormally expressed miRNAs, which expression profile discriminated ACT from NNAs. Among the 98 deregulated miRNAs, 17 presented significant associations with patients’ survival. In addition, higher expression levels of hsa-miR-630, -139-3p, -125a-3p, -574-5p, -596, -564, -1321, and -423-5p and lower expression levels of hsa-miR-377-3p, -126-3p, -410, -136-3p, -29b-3p, -29a-3p, -337-5p, -143-3p, and 140-5p were significantly associated with poor prognosis, tumor relapse, and/or death. Importantly, the expression profile of these 17 miRNAs stratified patients into two groups of ACTs with different clinical outcomes. Although some individual miRNAs exhibit potential prognostic values in ACTs, only the 17 miRNA-based expression clustering was considered an independent prognostic factor for five-year event-free survival (EFS) compared to other clinicopathological features. In conclusion, our study reports for the first time associations between miRNA profiles and childhood ACT prognosis, providing evidence that miRNAs could be useful biomarkers to discriminate patients with favorable and unfavorable clinical outcomes.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zehao Cai ◽  
Chunna Yu ◽  
Shenglan Li ◽  
Can Wang ◽  
Yaqiong Fan ◽  
...  

PurposeGlioma is a classical type of primary brain tumors that is most common seen in adults, and its high heterogeneity used to be a reference standard for subgroup classification. Glioma has been diagnosed based on histopathology, grade, and molecular markers including IDH mutation, chromosome 1p/19q loss, and H3K27M mutation. This subgroup classification cannot fully meet the current needs of clinicians and researchers. We, therefore, present a new subgroup classification for glioma based on the expression levels of Gβ and Gγ genes to complement studies on glioma and Gβγ subunits, and to support clinicians to assess a patient’s tumor status.MethodsGlioma samples retrieved from the CGGA database and the TCGA database. We clustered the gliomas into different groups by using expression values of Gβ and Gγ genes extracted from RNA sequencing data. The Kaplan–Meier method with a two-sided log-rank test was adopted to compare the OS of the patients between GNB2 group and non-GNB2 group. Univariate Cox regression analysis was referred to in order to investigate the prognostic role of each Gβ and Gγ genes. KEGG and ssGSEA analysis were applied to identify highly activated pathways. The “estimate” package, “GSVA” package, and the online analytical tools CIBERSORTx were employed to evaluate immune cell infiltration in glioma samples.ResultsThree subgroups were identified. Each subgroup had its own specific pathway activation pattern and other biological characteristics. High M2 cell infiltration was observed in the GNB2 subgroup. Different subgroups displayed different sensitivities to chemotherapeutics. GNB2 subgroup predicted poor survival in patients with gliomas, especially in patients with LGG with mutation IDH and non-codeleted 1p19q.ConclusionThe subgroup classification we proposed has great application value. It can be used to select chemotherapeutic drugs and the prognosis of patients with target gliomas. The unique relationships between subgroups and tumor-related pathways are worthy of further investigation to identify therapeutic Gβγ heterodimer targets.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zongxian Zhao ◽  
Shuliang Li ◽  
Shilong Li ◽  
Jun Wang ◽  
Hai Lin ◽  
...  

Abstract Background Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. Methods The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. Results CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). Conclusion CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
M Kibler ◽  
C Sato ◽  
J Heger ◽  
...  

Abstract Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (&lt;25) and CT-ADP (&gt;180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI &lt;25 and CT-ADP &gt;180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI &lt;25, and CT-ADP &gt;180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None


2021 ◽  
pp. 1-15
Author(s):  
Apostolos Tsiachristas ◽  
Antoinette Broad ◽  
Alice Coates ◽  
Surya Singh ◽  
Jane Fossey

Abstract The aim was to provide evidence of mortality and community care costs of people living in care homes and to investigate its association with mental health based on the Mental Health Clustering Tool (MHCT). In an observational study, 5,782 residents living in 104 care homes were followed from 2014 to 2016. Residents were categorised into four groups using the MCHT: three with mental health conditions, ‘non-psychotic’, ‘psychotic’ or ‘organic’; and one without mental health conditions, ‘non-clustered’. Generalised estimating equations were used to explore associations between mean community care costs over 6 months per patient and the clustering of residents into the four groups. Differences in survival rates of residents were plotted using Kaplan–Meier curves and tested with the log-rank test and Cox regression analysis. Community care costs were similar among residents with dementia (£431) and without mental health conditions (£407), while costs were higher among residents with non-psychotic (£762) and psychotic (£1,724) mental health conditions. After adjusting for patient and care home characteristics, residents with dementia were 30 per cent less likely to die compared with residents without mental health conditions. Similarly, residents with psychotic conditions and residents with non-psychotic conditions were 25 and 20 per cent less likely to die, respectively, than residents without mental health conditions. The MHCT seems to provide an informative stratification of care home residents with regards to survival and community care use.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peng Wang ◽  
Haihua Zhou ◽  
Gaohua Han ◽  
Qingtao Ni ◽  
Shengbin Dai ◽  
...  

Abstract Purpose To assess the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma and to investigate subgroups of patients suitable for adjuvant radiotherapy. Methods and materials Data from 785 patients with gastric adenocarcinoma who had undergone D1/D2 radical resection and adjuvant chemotherapy were collected, the site of first progression was determined, and the relationship between the rate of local recurrence and clinicopathologic features was analyzed. Results By the end of the follow-up period, progression was observed in 405 patients. Local recurrence was observed as the first progression in 161 cases. The local recurrence rate was significantly lower than the non-local progression rate (20.5% vs 31.5%, p=0.007). Multivariate Cox regression analysis showed a significant relationship among degree of differentiation, T stage, N stage, and rate of local recurrence. Conclusions Not all patients with gastric carcinoma required adjuvant radiotherapy. However, patients with poorly differentiated cancer cells, advanced T stage (T3/T4), and positive lymph nodes, which included patients in the T4N1-2M0 subgroup, were recommended for adjuvant radiotherapy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4084-4084
Author(s):  
Andrew X. Zhu ◽  
Josep M Llovet ◽  
Masahiro Kobayashi ◽  
Masafumi Ikeda ◽  
Marc Pracht ◽  
...  

4084 Background: In a phase 1b trial (NCT03006926), L + P had promising antitumor activity as first-line (1L) therapy in uHCC. We present exploratory biomarker analyses of circulating angiogenic factors and cytokines/chemokines related to the mechanism of action of L + P (ie, pharmacodynamic [PD] biomarkers), as well as biomarker correlations with clinical outcomes in patients (pts) with uHCC, from this trial. Methods: Pts received lenvatinib 12 mg/d (bodyweight [BW] >60 kg) or 8 mg/d (BW < 60 kg) PO + pembrolizumab 200 mg IV Q3W. Tumors were assessed using mRECIST or RECIST v1.1 per independent imaging review. Peripheral blood samples were collected before administration of study drug at baseline, cycle (C) 2, day (D) 1, C3D1, C4D1, and off-treatment. 43 Biomarkers were assayed in serum from 100 1L uHCC pts (excluding 4 pts from the dose-limiting toxicity part of the trial with prior sorafenib). Of these 43, 31 biomarkers (for which ≤20% of samples had measurements above/below the quantification limit of the assay) were included in the analyses. Changes in biomarker levels from baseline were evaluated via 1-sample Wilcoxon signed-rank test. Associations were explored between changes in biomarker levels and maximum tumor shrinkage (MTS) via the Spearman’s rank correlation test, objective response (OR; complete response + partial response) via the Wilcoxon rank sum test, and PFS via Cox regression analysis and log rank test. Data cutoff date for clinical endpoints was 7 August 2020. Results: Levels of PD biomarkers related to angiogenic signaling (VEGF increase/ANG2 decrease), FGF signaling (increase in FGF23/FGF19), and IFNγ signaling (increase in IFNγ, CXCL9/10/11) were changed significantly (adjusted P< 0.05) with L + P (C2D1–C4D1; except for FGF19 at C3D1). Significant decreases of TIMP1 and increases of MCP1 were observed at C4D1 during treatment; these were associated with greater MTS. Greater decreases in TIMP1 and greater increases in MCP1 were observed in pts with OR vs others. Changes in levels of the PD biomarkers ANG2, IL10, and VEGFR2 were found to be associated with PFS by dichotomized analysis. With tertile 2 cutoff, median PFS for pts in the group with greater decreases of ANG2 was 13.9 months vs 9.6 months for pts in the group with lesser decreases of ANG2 (unadjusted P= 0.002; HR 2.65, 95% CI 1.39–5.08). Conclusions: These are the first exploratory biomarker analyses for the single-arm study of L + P in pts with uHCC. Changes in serum biomarkers associated with angiogenic-, FGF-, and IFNγ-signaling pathways indicated target engagement of L + P. Decreases in TIMP1 and increases in MCP1 were associated with MTS and OR. Associations were found between longer PFS and a greater decrease in levels of ANG2. Angiogenesis inhibition and modulation of cancer immune response were observed with L + P. Further validation from independent studies is warranted. Clinical trial information: NCT03006926.


2018 ◽  
Vol 50 (3) ◽  
pp. 1041-1054 ◽  
Author(s):  
Ye Tao ◽  
Tianchang Tao ◽  
Neil Gross ◽  
Xuyun Peng ◽  
Ying Li ◽  
...  

Background/Aims: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC). Methods: The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival. Results: LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4). Conclusion: IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.


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