scholarly journals Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Carolina Torres ◽  
Ana Linares ◽  
Maria José Alejandre ◽  
Rogelio J. Palomino-Morales ◽  
Octavio Caba ◽  
...  

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1612
Author(s):  
Julie Earl ◽  
Emma Barreto ◽  
María E. Castillo ◽  
Raquel Fuentes ◽  
Mercedes Rodríguez-Garrote ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.


2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.


2021 ◽  
Author(s):  
Se Jun Park ◽  
Hyunho Kim ◽  
Kabsoo Shin ◽  
Tae Ho Hong ◽  
Ja Hee Suh ◽  
...  

Abstract BackgroundAccording to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who previously treated gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to hematological toxicity. There has been limited information on the clinical benefit and toxicity of this regimen in a real-world setting. Herein, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure.MethodsWe conducted a single institution retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80mg/m2) with 5-FU/LV every 2 weeks. ResultsFifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% confidence interval [CI] 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced any grade 3 or 4 adverse events. Most common grade 3 or 4 adverse event was neutropenia (58.8%) and most non-hematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4).ConclusionsNal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, after gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Trial registration Retrospectively registered


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Sun ◽  
Xiangyu Kong ◽  
Yiqi Du ◽  
Zhaoshen Li

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high rate of mortality and poor prognosis. Numerous studies have proved that microRNA (miRNA) may play a vital role in a wide range of malignancies, including PDAC, and dysregulated miRNAs, including circulating miRNAs, are associated with PDAC proliferation, invasion, chemosensitivity, and radiosensitivity, as well as prognosis. Greater understanding of the roles of miRNAs in PDAC could provide insights into this disease and identify potential diagnostic markers and therapeutic targets. The current review focuses on recent advances with respect to the roles of miRNAs in PDAC and their practical value.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shan Liang ◽  
Zhulin Yang ◽  
Daiqiang Li ◽  
Xiongying Miao ◽  
Leping Yang ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3 expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues were measured by immunohistochemical methods. Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P<0.01). The percentage of cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P<0.05orP<0.01). Positive DDX3 expression is associated with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that positive Nectin-2 and DDX3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC patients. In conclusion, positive Nectin-2 and DDX3 expression are associated with the progression and poor prognosis in PDAC patients.


2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Syed Hasan ◽  
Rojymon Jacob ◽  
Upender Manne ◽  
Ravi Paluri

Biomarkers play an essential role in the management of patients with invasive cancers. Pancreatic ductal adenocarcinoma (PDC) associated with poor prognosis due to advanced presentation and limited therapeutic options. This is further complicated by absence of validated screening and predictive biomarkers for early diagnosis and precision treatments respectively. There is emerging data on biomarkers in pancreatic cancer in past two decades. So far, the CA 19-9 remains the only approved biomarker for diagnosis and response assessment but limited by low sensitivity and specificity. In this article, we aim to review current and future biomarkers that has potential serve as critical tools for early diagnostic, predictive and prognostic indications in pancreatic cancer.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4037-4037
Author(s):  
Maithili A Shethia ◽  
Aparna Hegde ◽  
Xiao Zhou ◽  
Michael J. Overman ◽  
Saroj Vadhan-Raj

4037 Background: Patients (pts) with pancreatic cancer are at high risk for VTE, and the occurrence of VTE can affect pts’ prognosis. The purpose of this study was to evaluate the incidence of VTE and the impact of timing of VTE (early vs. late) on survival. Methods: Medical record of 260 pts with pancreatic cancer, newly referred to UT MDACC during one year period from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE during a 2-year follow-up period from the date of diagnosis. All VTE episodes were confirmed by radiologic studies. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional hazard models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE during the 2-year follow-up. The median age of the pts with VTE was 61 years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27 (57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts had recurrent VTE during the study period. Median follow-up time for OS was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis showed that those who developed VTE earlier (within 30 or 90 days) had shorter median overall survival (OS) compared with those who had VTE beyond these time points. The hazard ratios, 95% CI, and median OS at 1 year are summarized in the table below. Conclusions: The incidence of VTE is high in pts with pancreatic cancer. The timing of VTE had a significant impact on OS; pts who had an early development of VTE had a shorter overall survival. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15756-e15756 ◽  
Author(s):  
Leszek Kraj ◽  
Andrzej Śliwczyński ◽  
Joanna Krawczyk-Lipiec ◽  
Krzysztof Woźniak ◽  
Anna Waszczuk-Gajda ◽  
...  

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p < 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.


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