scholarly journals Serum  JAK/STAT profile is related to the IL expression but not with the outcome in pancreatic adenocarcinoma patients

2021 ◽  
Vol 67 (3) ◽  
pp. 107-112
Author(s):  
Livia Petrusel ◽  
Maria Ilies ◽  
Daniel Leucuta ◽  
Ioana Rusu ◽  
Andrada Seicean ◽  
...  
Keyword(s):  
Cox Regression ◽  
Serum Levels ◽  
Ductal Adenocarcinoma ◽  
Analysis Model ◽  
Inflammatory Status ◽  
Metastasis Development ◽  
Node Metastases ◽  
Stat Pathway

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

A High C-Reactive Protein Level on Postoperative Day 7 is Associated with Poor Survival of Patients with Pancreatic Ductal Adenocarcinoma after Resection

2021 ◽  
pp. 000313482110234
Author(s):  
Masaji Tani ◽  
Hiroya Iida ◽  
Hiromitsu Maehira ◽  
Haruki Mori ◽  
Toru Miyake ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Ductal Adenocarcinoma ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Retrospective View ◽  
Node Metastases ◽  
Common Malignancy

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy. While inflammation-related biomarkers influence patient survival after resection, it has not been known whether postoperative inflammations affect the survival of PDAC patients or not. Methods It was investigated whether the universal biomarkers on postoperative day (POD) 7 affect the survival of PDAC patients in the retrospective view, and univariate and multivariate analyses were performed via the Cox regression method. Results Overall, 108 consecutive patients underwent resection; 98 (90.7%) had T3 disease and 73 (67.6%) had lymph node metastases. Thirty-four patients (31.5%) experienced postoperative complications. Compared with preoperative values, the white blood cell count and C-reactive protein (CRP) level on POD 7 were significantly elevated ( P < .001 for both); conversely, the lymphocyte count was significantly reduced ( P < .001). Among 108 patients, 72 received adjuvant chemotherapy. The median overall survival was 21.0 months; the 5-year survival rate was 22.3%. On multivariate analysis, receiving adjuvant chemotherapy and low CRP levels on POD 7 (<7.6 mg/dL) were prognosticators of better survival. However, the CD classification was not a prognosticator of survival after resection. Conclusions Adjuvant chemotherapy and postoperative low CRP levels on POD 7 were prognosticators of better survival of PDAC patients after resection. Surgeons should be aware of managing postoperative infections because a high postoperative CRP level is related with unfavorable survival.

The clinical utility of neuron-specific enolase serum levels as a biomarker for Merkel cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9570-9570 ◽  
Author(s):  
Linde M. van Veenendaal ◽  
Eduardo Bertolli ◽  
Catharina M. Korse ◽  
W. Martin. C. Klop ◽  
Margot Et Tesselaar ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Cox Regression ◽  
Neuron Specific Enolase ◽  
Distant Metastases ◽  
Serum Levels ◽  
Optimal Level ◽  
Rank Test ◽  
Merkel Cell

9570 Background: To date no adequate biomarker for Merkel Cell carcinoma (MCC) has been identified. The introduction of immunotherapy (IT) for metastatic MCC increases the need for a biomarker. Serum Neuron-specific enolase (NSE) has already been tested and is commonly used as a biomarker for several small cell malignancies. However, the role of NSE in MCC is still unclear. Aim: To investigate the role of NSE as a biomarker in MCC. Methods: A prospective cohort of MCC patients treated from 2016 to July 2018 was analyzed. Kaplan Meier curves with log rank test, Cox regression and mixed models were used to analyze NSE. A separate evaluation was performed for patients treated with IT. Results: A total of 78 patients (42 males, median age 71 years, stage I&II, III and IV MCC in 37(47%), 39(50%) and 2(3%) patients at time of diagnosis with 474 NSE levels (median 15 ; IQR 12,6-22 ng/ml were included. Baseline NSE (n=36) had no influence on survival or progression. During follow-up (FU) NSE levels correlated with tumorload (p=0,01) with increase of 15 ng/ml per class (no tumorload, localized MCC, nodal and distant metastases, respectively). NSE level during FU was able to detect progression (AUC 0,89). Several cut off values were evaluated. A NSE of 18,2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98% to detect progression). During IT (n=16; 195 NSE values) all complete responders (n=7) had a normalized NSE (<18,2 ng/ml), all partial responders (n=3) had a decreasing NSE. In non-responders (n=6) all NSE levels remained elevated, one patient responded after switching to different IT with normalizing NSE values. Conclusions: NSE seems to be a valuable biomarker in MCC. NSE correlates with tumorload; is able to rule out progression and distinguishes responders from non-responders during IT.

scholarly journals Role of systemic immune-inflammation index in patients treated with salvage radical prostatectomy

2021 ◽  
Author(s):  
Pawel Rajwa ◽  
Victor M. Schuettfort ◽  
Fahad Quhal ◽  
Keiichiro Mori ◽  
Satoshi Katayama ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Prognostic Value ◽  
Multimodal Therapy ◽  
Cox Regression ◽  
Cancer Specific Survival ◽  
Node Metastases ◽  
Immune Inflammation ◽  
Salvage Radical Prostatectomy ◽  
Predictive And Prognostic Value

Abstract Purpose To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP). Materials and methods This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker. Results A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45–7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33–4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12–103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70–27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23–398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67–21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1). Conclusions In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance.

scholarly journals The Role of Hyponatraemia Before Surgery in Patients With Radical Resected Pancreatic Cancer

2020 ◽  
Vol 14 ◽  
pp. 117955492093660
Author(s):  
Rossana Berardi ◽  
Silvia Rinaldi ◽  
Giulio Belfiori ◽  
Stefano Partelli ◽  
Stefano Crippa ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cox Regression ◽  
Radical Surgery ◽  
Ductal Adenocarcinoma ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Kaplan Meier ◽  
Negative Prognostic Factor ◽  
Significant Difference

Objectives: Hyponatraemia represents a negative prognostic factor in patients with cancer. The aim of this study was to assess, for the first time, the role of hyponatraemia in patients undergoing radical surgery for pancreatic ductal adenocarcinoma. Methods: A total of 89 patients with stage I-III pancreatic ductal adenocarcinoma underwent radical surgery between November 2012 and October 2014. Relapse-free survival (RFS) and disease-specific survival (DSS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses. Fisher exact test was used to estimate correlation between variables. Results: In total, 12 patients (14%) presented with hyponatraemia at diagnosis. The median DSS was 20 months in patients with hyponatraemia and not reached in patients with eunatraemia ( P < .1073), while a statistical significant difference was observed in terms of median RFS (10 months vs 17 months, respectively; P = .0233). Considering clinical features (hyponatraemia, smoke and alcoholic habit, diabetes, pain, and jaundice), patients with 4 or more of these factors had a worse prognosis (mDSS: 30 months vs not reached; hazard ratio [HR]: 0.40, 95% confidence interval [CI] = 0.16-0.80; P = .0120). Conclusions: The presence of hyponatraemia and its prompt correction at the diagnosis time should be considered for the correct management of patients with pancreatic carcinoma.

scholarly journals Integrative Characterization of the Role of IL27 In Melanoma Using Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunyu Dong ◽  
Dan Dang ◽  
Xuesong Zhao ◽  
Yuanyuan Wang ◽  
Zhijun Wang ◽  
...  
Keyword(s):  
Cox Regression ◽  
Rank Test ◽  
Survival Outcomes ◽  
Dual Roles ◽  
Functional Annotations ◽  
T Cell Infiltration ◽  
Predictors Of Response ◽  
Sensitivity Data

BackgroundIL27 has been reported to play dual roles in cancer; however, its effects on the tumor microenvironment (TME), immunotherapy, and prognosis in melanoma remain largely unclear. This study was aimed to uncover the effects of IL27 on TME, immunotherapy and prognosis in patients with melanoma.MethodsRNA-seq data, drug sensitivity data, and clinical data were obtained from TCGA, GEO, CCLE, and CTRP. Log-rank test was used to determine the survival value of IL27. Univariate and multivariate Cox regression analyses were employed to determine the independent predictors of survival outcomes. DAVID and GSEA were used to perform gene set functional annotations. ssGSEA was used to explore the association between IL27 and immune infiltrates. ConsensusClusterPlus was used to classify melanoma tissues into hot tumors or cold tumors.ResultsClinically, IL27 was negatively correlated with Breslow depth (P = 0.00042) and positively associated with response to radiotherapy (P = 0.038). High IL27 expression showed an improved survival outcome (P = 0.00016), and could serve as an independent predictor of survival outcomes (hazard ratio: 0.32 - 0.88, P = 0.015). Functionally, elevated IL27 expression could induce an enhanced immune response and pyroptosis (R = 0.64, P = 1.2e-55), autophagy (R = 0.37, P = 7.1e-17) and apoptosis (R = 0.47, P = 1.1e-27) in patients with melanoma. Mechanistically, elevated IL27 expression was positively correlated with cytotoxic cytokines (including INFG and GZMB), enhanced immune infiltrates, and elevated CD8/Treg ratio (R = 0.14, P = 0.02), possibly driving CD8+ T cell infiltration by suppressing β-catenin signaling in the TME. Furthermore, IL27 was significantly associated with hot tumor state, multiple predictors of response to immunotherapy, and improved drug response in patients with melanoma.ConclusionsIL27 was correlated with enriched CD8+ T cells, desirable therapeutic response and improved prognosis. It thus can be utilized as a promising modulator in the development of cytokine-based immunotherapy for melanoma.

scholarly journals The Role of Autophagy in Pancreatic Cancer—Recent Advances

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 7 ◽  
Author(s):  
Maria New ◽  
Sharon Tooze
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Large Body ◽  
Ductal Adenocarcinoma ◽  
Improve Treatment ◽  
Recent Advances ◽  
Dismal Prognosis ◽  
Tumor Survival ◽  
Metastasis Development

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with a 5-year survival rate of only 9%, despite ongoing efforts to improve treatment. This dismal prognosis is due to the difficulty of early stage diagnosis, drug resistance, and likelihood of metastasis development. It is therefore of great importance to identify appropriate therapeutic targets and gain a greater understanding of PDAC biology. Autophagy is a membrane-mediated degradation and recycling mechanism, which is crucial for cell homeostasis. There is evidence for both a tumor-suppressive and a tumor-promoting role of autophagy in cancer, and this is likely context dependent. Within PDAC, a large body of evidence points towards autophagy being required for tumor survival and metabolism. In this review, we describe the recent advances in the understanding of the role and regulation of autophagy in PDAC.

Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 144-144
Author(s):  
Paula Kappler ◽  
Stefan Brunotte ◽  
Philipp Ivanyi ◽  
Michael A. Morgan ◽  
Christoph W. Reuter
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Cox Regression ◽  
Specific Antigen ◽  
Serum Levels ◽  
Prognostic Role ◽  
Cycle Number ◽  
Prognostic Risk Factors ◽  
The Impact

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res & Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to < 0.01 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR > 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values < 0.01 pg/mL were independent prognostic risk factors for OS (p < 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

scholarly journals Rethinking the TNM Classification Regarding Direct Lymph Node Invasion in Pancreatic Ductal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 201
Author(s):  
Fiona Speichinger ◽  
Mihnea P. Dragomir ◽  
Simon Schallenberg Schallenberg ◽  
Florian N. Loch Loch ◽  
Claudius E. Degro Degro ◽  
...  
Keyword(s):  
Lymph Node ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tnm Classification ◽  
Ductal Adenocarcinoma ◽  
Prognostic Role ◽  
Tumour Metastasis ◽  
Direct Invasion ◽  
Node Metastases ◽  
The Difference

Mechanisms of lymph node invasion seem to play a prognostic role in pancreatic ductal adenocarcinoma (PDAC) after resection. However, the 8th edition of the TNM classification of the American Joint Committee on Cancer (AJCC) does not consider this. The aim of this study was to analyse the prognostic role of different mechanisms of lymph node invasion on PDAC. One hundred and twenty-two patients with resected PDAC were examined. We distinguished three groups: direct (per continuitatem, Nc) from the main tumour, metastasis (Nm) without any contact to the main tumour, and a mixed mechanism (Ncm). Afterwards, the prognostic power of the different groups was analysed concerning overall survival (OS). In total, 20 patients displayed direct lymph node invasion (Nc = 16.4%), 44 were classed as Nm (36.1%), and 21 were classed as Ncm (17.2%). The difference in OS was not statistically significant between N0 (no lymph node metastasis, n = 37) and Nc (p = 0.134), while Nm had worse OS than N0 (p < 0.001). Direct invasion alone had no statistically significant effect on OS (p = 0.885). Redefining the N0 stage by including Nc patients showed a more precise OS prediction among N stages (p = 0.001 vs. p = 0.002). Nc was more similar to N0 than to Nm; hence, we suggest a rethinking of TNM classification based on the mechanisms of lymph node metastases in PDAC. Overall, this novel classification is more precise.

Plasma KRAS as a biomarker for pancreatic ductal adenocarcinoma (PDAC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 316-316 ◽  
Author(s):  
Benjamin A. Krantz ◽  
Dana Tsui ◽  
Maeve Aine Lowery ◽  
Marinela Capanu ◽  
Kenneth H. Yu ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Cancer Center ◽  
Peritoneal Disease ◽  
Kras Mutations ◽  
Factors Affecting ◽  
Droplet Pcr ◽  
Node Metastases ◽  
Predictive Assay

316 Background: PDAC needs validated diagnostic biomarkers for early detection and predictive markers for outcome. As 95% of PDACs harbor KRAS mutations (mKRAS), circulating tumor DNA (ctDNA) has potential utility in PDAC. We assessed the ability to detect and correlate mKRAS in a metastatic PDAC cohort from Memorial Sloan Kettering Cancer Center. Methods: 10 mL of whole blood was collected. cfDNA was extracted with QIAmp or QIAsymphony DNA extraction kits (Qiagen, Valencia, CA). Directed (KRAS G12D, G12R, G12V, Q61H) or multiplex (G12A, G12C, G12D, G12R, G12S, G12V, G13D) digital droplet PCR (ddPCR) was performed with Raindrop Plus (Raindance Technologies, Billerica, MA) or QX200 (BioRad, Hercules, CA) ddPCR systems. Number and size of liver, lung and lymph node metastases, peritoneal disease (mild, moderate, severe), ascites (trace, small, large) and bone mets (Y/N) were assessed by CT scan. Results: See table. 21 (55%) had detectable ctDNA (ctDNA(+)) with mean mutant allele fraction of 4.5% (0.015-36.8). ctDNA (+) vs (-) PFS and OS from collection were 6.9 and 8.4 months vs. 9.9 and 10.5 (p=0.89 for both). CA19-9, PFS and OS did not correlate with ctDNA tertile (p=0.15, 0.54 & 0.50). On treatment and disease activity were not associated with ctDNA status (p= 0.20 & 0.60). Number and size of liver mets were associated with ctDNA (+) (p=0.006 & 0.007). Conclusions: ctDNA KRAS detection was measurable in metastatic disease with rates consistent with other PDAC reports. Median PFS, OS were lower in ctDNA (+) group but not statistically significant in this diverse cohort. Number and size of liver metastases were significantly higher in ctDNA (+). Future study should focus on practice changing applications with standardized collection, intra-patient comparisons and role of liver disease burden. We have initiated studies to evaluate plasma KRAS prior to and during treatment to address its value as a predictive assay and explore factors affecting ctDNA detection. [Table: see text]

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