scholarly journals Serum levels of circulating microRNA-107 are elevated in patients with early-stage HCC

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247917
Author(s):  
Sven H. Loosen ◽  
Mirco Castoldi ◽  
Markus S. Jördens ◽  
Sanchary Roy ◽  
Mihael Vucur ◽  
...  
Keyword(s):  
Overall Survival ◽  
Early Stage ◽  
Tumor Resection ◽  
Serum Levels ◽  
Circulating Microrna ◽  
Liver Malignancy ◽  
Clear Trend ◽  
Disease Etiology ◽  
Expression Levels

Background Early detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). However, easily accessible biomarkers facilitating an early diagnosis of HCC as well as a reliable risk prediction are currently missing. The microRNA(miR)-107 has recently been described as a driver of HCC in both murine and human HCC but data on circulating miR-107 in HCC patients are scarce. In the present study, we evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC. Methods The Kmplot bioinformatic tool was used to query publicly available databases (including TCGA, GEO and EGA) in order to analyse the prognostic value of tumoral miR-107 expression in HCC patients (n = 372). Serum levels of miR-107 were measured by qPCR in n = 45 HCC patients undergoing surgical tumor resection (n = 37) or LT (n = 8) as well as n = 18 healthy control samples. Results were correlated with clinical data. Results A high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48–0.99, p = 0.041). In addition, serum levels of miR-107 were significantly higher in HCC patients when compared to healthy controls. However, miR-107 serum levels in HCC patients were independent of different disease etiology, tumor stage or tumor grading. HCC patients with baseline miR-107 expression levels above a calculated ideal prognostic cut-off value (9.82) showed a clear trend towards an impaired overall survival (p = 0.119). Conclusion Tumoral miR-107 expression levels are a potential prognostic marker in early stage HCC. Furthermore, we describe a potential role of circulating miR-107 levels as a diagnostic biomarker in patients with early-stage HCC.

scholarly journals Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6569
Author(s):  
Christoph Roderburg ◽  
Sven H. Loosen ◽  
Jan Bednarsch ◽  
Patrick H. Alizai ◽  
Anjali A. Roeth ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Tumor Biology ◽  
Tumor Resection ◽  
Postoperative Outcome ◽  
Serum Levels ◽  
Strong Trend ◽  
Programmed Cell Death 1 ◽  
Early Tumor ◽  
Circulating Levels

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.

scholarly journals The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shaohui Zong ◽  
Gaofeng Zeng ◽  
Ye Fang ◽  
Jinzhen Peng ◽  
Yong Tao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Hind Limb ◽  
Rating Scale ◽  
Serum Levels ◽  
Spinal Cord Tissue ◽  
Expression Levels ◽  
Stat3 Signaling ◽  
Cord Injury ◽  
Disease Stages

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.

scholarly journals Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiang Chen ◽  
Hongyu Li ◽  
Wenda Xu ◽  
Xiaozhong Guo
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Potential Role ◽  
Early Stage ◽  
Serum Levels ◽  
Diagnostic Efficacy ◽  
Diagnostic Biomarkers ◽  
The Poor

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

Increased Expression of KISS1 and KISS1 Receptor in Human Granulosa Lutein Cells—Potential Pathogenesis of Polycystic Ovary Syndrome

2018 ◽  
Vol 26 (11) ◽  
pp. 1429-1438 ◽  
Author(s):  
Kai-Lun Hu ◽  
Hongcui Zhao ◽  
Zheying Min ◽  
Yilei He ◽  
Tianjie Li ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Expression Patterns ◽  
Serum Levels ◽  
Recent Experimental Data ◽  
Ovary Syndrome ◽  
Expression Levels ◽  
Highly Correlated

Kisspeptins are a family of neuropeptides that are essential for fertility. Recent experimental data suggest a putative role of kisspeptin signaling in the direct control of ovarian function. To explore the expression of KISS1 and KISS1 receptor (KISS1R) in human granulosa lutein cells and the potential role of KISS1/KISS1R system in the pathogenesis of polycystic ovary syndrome (PCOS), we measured the concentration of KISS1 in follicular fluid, the expression of KISS1 and KISS1R in granulosa lutein cells, and the circulating hormones. The expression levels of KISS1 and KISS1R were significantly upregulated in human granulosa lutein cells obtained from women with PCOS. The expression levels of KISS1 in human granulosa lutein cells highly correlated with those of KISS1R in non-PCOS patients, but not in patients with PCOS, most likely due to the divergent expression patterns in women with PCOS. Additionally, the expression levels of KISS1 highly correlated with the serum levels of anti-Müllerian hormone (AMH). The expression levels of KISS1 and KISS1R, as well as the follicular fluid levels of KISS1, were not significantly different between the pregnant and nonpregnant patients in both PCOS and non-PCOS groups. In conclusion, the increased expression of KISS1 and KISS1R in human granulosa lutein cells may contribute to the pathogenesis of PCOS. The expression levels of KISS1 highly correlated with the serum levels of AMH. The KISS1 and KISS1R system in the ovary may not have a remarkable role in predicting the in vitro fertilization (IVF) outcome.

Soluble urokinase plasminogen activator receptor (suPAR) as a novel biomarker in patients undergoing resection of pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 248-248
Author(s):  
Sven H Loosen ◽  
Marcel Binnebösel ◽  
Thomas Longerich ◽  
Christoph Roderburg ◽  
Christian Trautwein ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Pancreatic Adenocarcinoma ◽  
Tumor Resection ◽  
Serum Levels ◽  
Healthy Controls ◽  
Urokinase Plasminogen Activator Receptor ◽  
Tissue Samples ◽  
Pdac Tissue ◽  
Plasminogen Activator Receptor

248 Background: Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after successful R0 tumor resection, some patients are still facing an unfavourable prognosis underlining the need for better preoperative stratification algorithms. The soluble urokinase plasminogen activator receptor (suPAR) was recently described as a promising new biomarker for different clinical conditions including cancer. Here, we evaluated the potential role of circulating suPAR as a biomarker in patients undergoing resection of PDAC. Methods: Expression levels of uPAR, the membrane-bound source of circulating suPAR, were analysed in PDAC tissue samples using IHC. Serum levels of suPAR were measured by ELISA in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Results were correlated with clinical data. Results: Correlating with a high immunohistochemical expression of uPAR in PDAC tissue samples, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls. Importantly, patients with high preoperative suPAR levels above a calculated cut-off value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients’ characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury after surgery. Conclusions: Our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.

scholarly journals MA 13.06 New Risk Factors for Overall Survival After SBRT in Early Stage NSCLC: A Role of RT Plan Optimization

2017 ◽  
Vol 12 (11) ◽  
pp. S1853 ◽  
Author(s):  
F. Kong ◽  
Y. Liu ◽  
H. Zhang ◽  
H. Yao ◽  
A. Cerra-Franco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Early Stage ◽  
Early Stage Nsclc ◽  
Plan Optimization

scholarly journals Prognostic Role of Tissue and Circulating MicroRNA-200c in Malignant Tumors: a Systematic Review and Meta-Analysis

2015 ◽  
Vol 35 (3) ◽  
pp. 1188-1200 ◽  
Author(s):  
Yingjie Shao ◽  
Yiting Geng ◽  
Wendong Gu ◽  
Jin Huang ◽  
Honglei Pei ◽  
...  
Keyword(s):  
Systematic Review ◽  
Malignant Tumors ◽  
Early Stage ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Circulating Microrna ◽  
Prognostic Role ◽  
Altered Expression ◽  
High Level

Background: Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers. Methods: Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation. Results: A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease. Conclusion: This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors.

scholarly journals Study on the Role of Cytc in Response to BmNPV Infection in Silkworm, Bombyx mori (Lepidoptera)

2019 ◽  
Vol 20 (18) ◽  
pp. 4325 ◽  
Author(s):  
Xue-Yang Wang ◽  
Kang-Hui Wu ◽  
Hui-Lin Pang ◽  
Ping-Zhen Xu ◽  
Mu-Wang Li ◽  
...  
Keyword(s):  
Bombyx Mori ◽  
Early Stage ◽  
Malpighian Tubule ◽  
Infection Process ◽  
Insect Vector ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Mitochondrial Apoptosis Pathway

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens of the silkworm. Cytochrome c (cytc) showed a significant response to BmNPV infection in our previous transcriptome study. However, little is known about the role of Bombyx mori cytc (Bmcytc) in resistance to BmNPV infection. In this study, the expression levels analysis of Bmcytc showed stable expression levels in selected tissues of the resistant strain AN following BmNPV infection, while there was downregulation in the susceptible strain p50, except in the malpighian tubule. To further study the role of Bmcytc in viral infection, Bmcytc was knocked down with siRNA in vitro, resulting in significant downregulation of selected downstream genes of the mitochondrial pathway, including Bmapaf, Bmcaspase-Nc, and Bmcaspase-1; this was also confirmed by overexpression of Bmcytc using the pIZT/V5-His-mCherry insect vector, except Bmcaspase-1. Moreover, knockdown of Bmcytc significantly promoted the infection process of BmNPV in vitro, while the infection was inhibited by overexpression of Bmcytc at the early stage and subsequently increased rapidly. Based on these results, we concluded that Bmcytc plays a vital role in BmNPV infection by regulating the mitochondrial apoptosis pathway. Our work provides valuable data for the clarification of the mechanism of silkworm resistance to BmNPV infection.

Stage and histology influence the relationship between MDM2 promoter polymorphism and esophageal cancer and overall survival (OS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21047-21047
Author(s):  
H. J. Mackay ◽  
P. Bradbury ◽  
K. Asomaning ◽  
W. Zhou ◽  
M. Kulke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Early Stage ◽  
Disease Stage ◽  
Advanced Stage ◽  
Mdm2 Snp309 ◽  
Prognostic Role ◽  
Histologic Subtype ◽  
The Relationship

21047 Background: A single nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to affect OS of advanced stage gastric adenocarcinoma (AD) and early stage squamous (SQ) cell carcinoma of the lung. The aim of this study was to evaluate the role of this polymorphism in the prognosis of esophageal cancer, another aerodigestive cancer. Methods: 150 early stage (E) and 118 locally advanced stage (LA) esophageal cancers were genotyped for MDM2 SNP309 using Taqman. The primary endpoint was overall survival (OS). Results: E disease: n=23 stage I; n=127 stage II. LA disease: n=93, Stage III; n=25, Stage IVA. AD comprised 215 (81%), while SQ comprised 45 (17%) of cases; 8 (3%) had poorly differentiated tumors. Median follow-up = 32 months. Median OS were 36 and 21 months for E and LA disease, respectively. Both histology and disease stage affected the relationship between SNP309 and esophageal cancer OS (see Table ). The wildtype T/T genotype conferred a worse OS in E patients (log-rank, p=0.03), especially those with AD (log-rank, p=0.003). In Cox proportional hazards interaction analyses, after adjusting for age, gender, stage and PS, there were statistically significant interactions between MDM2 SNP309 and disease stage (interaction p=0.004) and between MDM2 SNP309 and histologic subtype (AD vs. SQ)(interaction p=0.02). Thus, the direction of SNP309 association from our AD and E esophageal cancer patients are opposite to those of our SQ and LA esophageal cancer patients. However, our SQ and LA results are similar to the SQ lung cancer and advanced stage gastric cancers previously reported. This suggests that biologic mechanisms underpinning the prognostic role of SNP309 are dependent on extent of disease and histologic subtype. Conclusion: Histology and disease stage interact with the prognostic role of MDM2 SNP309 polymorphism in esophageal cancer OS. [Table: see text] No significant financial relationships to disclose.

The role of gamma-glutamyltransferase in malignant transformation and prognosis of ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Richard Schwameis ◽  
Gerda Hofstetter ◽  
Stefanie Aust ◽  
Stephan Polterauer ◽  
Nicole Concin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Multivariable Analysis ◽  
Serum Levels ◽  
Cancer Tissue ◽  
Borderline Tumor ◽  
Advanced Tumor Stage ◽  
Gamma Glutamyltransferase ◽  
Ovarian Cancer Tissue

e16524 Background: Gamma-glutamyltransferase (GGT) – a membrane bound enzyme crucially involved in the cell’s detoxification pathway and apoptotic balance – is involved in tumor development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. Methods: In this multi-center study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n = 567) and borderline tumor of the ovary (BTO, n = 67). GGT serum levels were associated with clinico-pathological parameters and uni- and multivariate survival analyses were performed.Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. Results: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 [38.24] U/L) than in patients with BTO (20.01 [12.78] U/L, p = 0.01). High GGT serum levels were associated with advanced FIGO stage (p<0.001) and with worse overall survival in univariate (p < 0.001) and multivariable analysis (p=0.02, HR 1.2 [1.1-1.5]). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumor tissue and observed an association between these two parameters (p = 0.03). Conclusions: High pre-therapeutic GGT serum levels are associated with advanced tumor stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. GGT expression in ovarian cancer tissue is reflected in GGT serum levels.

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