Abstract 2160: PTEN deletion is associated with metastatic disease and worse prognosis in pancreatic cancer

2015 ◽  
Author(s):  
Martin Wartenberg ◽  
Irene Centeno ◽  
Inti Zlobec ◽  
Alessandro Lugli ◽  
Aurel Perren ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Disease ◽  
Pten Deletion ◽  
Worse Prognosis

scholarly journals B2M overexpression correlates with malignancy and immune signatures in human gliomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Zhang ◽  
Biqi Cui ◽  
Yulai Zhou ◽  
Xinxing Wang ◽  
Wantao Wu ◽  
...  
Keyword(s):  
Critical Role ◽  
Cell Types ◽  
Potential Candidate ◽  
Egfr Amplification ◽  
Immune Signatures ◽  
Idh Mutations ◽  
Pten Deletion ◽  
R Project ◽  
Patient Prognosis ◽  
Worse Prognosis

AbstractBecause of the limited treatment strategy of gliomas, the key of diagnosis and treatment is finding new molecular biomarkers. Here, we explored the potential of β2-microglobulin (B2M) to serve as a hopeful candidate for immunotherapy or diagnostic biomarker in gliomas. The genomic profiles, clinical characteristics, and immune signatures were analyzed based on TCGA and CGGA databases. We carried out the whole statistical analyses using R project. High B2M expression correlated with worse prognosis. Somatic mutations of gliomas with high B2M expression are associated with PTEN deletion and EGFR amplification. Isocitrate dehydrogenase (IDH) mutations accounted for 82% in gliomas with low B2M expression. In addition, B2M positively correlated with ESTIMATE scores, interacted with infiltrating immune and stromal cell types. B2M also suppressed anti-tumor immunity through immune related processes. Meanwhile, B2M was associated with immune checkpoint molecules and inflammatory activities. Finally, functional annotation of the identified B2M related genes verified that B2M was a potential candidate for immunotherapy. We confirmed that B2M played a critical role in tumor progression, patient prognosis and immunotherapy of gliomas.

Development of extracellular vesicles-based classifier for detection of early-stage bladder, ovarian, and pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Extracellular Vesicles ◽  
Metastatic Disease ◽  
Cancer Detection ◽  
Early Stage ◽  
Expression Patterns ◽  
Stepwise Logistic Regression ◽  
Liquid Biopsies ◽  
Cancer Early Detection

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

scholarly journals Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

2018 ◽  
Vol 25 (4) ◽  
pp. 1000-1008 ◽  
Author(s):  
Colin M. Court ◽  
Jacob S. Ankeny ◽  
Shonan Sho ◽  
Paul Winograd ◽  
Shuang Hou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Occult Metastatic Disease

The Tumour Marker CA 195 in Colorectal and Pancreatic Cancer

1991 ◽  
Vol 6 (4) ◽  
pp. 241-246 ◽  
Author(s):  
P.M. Sagar ◽  
O.M. Taylor ◽  
E.H. Cooper ◽  
E.A. Benson ◽  
M.J. Mcmahon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Serum Level ◽  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Initial Level ◽  
Tumour Marker ◽  
Tumour Markers ◽  
Normal Range ◽  
Unresectable Disease

The aim of this study was to measure the serum level of the tumour markers CA 195 and CEA in patients with either colorectal or pancreatic cancer both before and at serial intervals after operation. CA 195 and CEA were measured in 199 patients with colorectal cancer and 52 patients with pancreatic cancer. The median concentrations of CA 195 were 3.0 u/ml (interquartile range 3.0-4.5 u/ml) in patients with a Dukes’ stage A lesion, 5.8 u/ml (3.0-18.2 u/ml) in patients with a Dukes’ stage B lesion, 6.1 u/ml (3.0-24.7 u/ml) in patients with a Dukes’ stage C and 23.8 u/ml (11.1-409.0 u/ml) in patients with metastatic disease (normal range 0-7 u/ml). The median levels of CEA were 2.6 ng/ml (1.7-3.3 ng/ml) for Dukes’ stage A, 3.3 ng/ml (1.7-7.2 ng/ml) for Dukes’ stage B, 3.7 ng/ml (2.2-7.9 ng/ml) for Dukes’ stage C and 34.5 ng/ml (13.3-289.4 ng/ml) for metastatic disease. A rising level of CA 195 or CEA after operation suggested recurrence of the tumour. In none of these patients was the recurrence operable. In patients with pancreatic adenocarcinoma, the level of CA 195 was significantly higher in patients with metastatic disease but it did not discriminate between resectable and unresectable disease. The duration of survival correlated with the initial level of CA 195 (Rs = –0.66, p < 0.001).

Correlation of SMAD4 mutational status and local or metastatic progression in patients with pancreatic cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14730-e14730
Author(s):  
Olfa Derbel ◽  
Arnaud de la Fouchardière ◽  
Julien Peron ◽  
Michel Rivoire ◽  
Françoise Desseigne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Disease ◽  
Expression Profiles ◽  
Locally Advanced ◽  
Chemotherapeutic Agents ◽  
Clinicopathological Parameters ◽  
Molecular Heterogeneity ◽  
Metastatic Progression ◽  
Molecular Features ◽  
Mutational Status

e14730 Background: Pancreatic cancer remains resistant to many key cytotoxic chemotherapeutic agents and novel targeted therapies. The molecular heterogeneity of this cancer may account for therapy failures to date, although the growing arsenal of novel targeted agents could translate into patient survival. A better understanding of the cellular and molecular features of advanced disease will afford new opportunities for investigation, therapeutic intervention and clinical management of patients afflicted with pancreatic cancer. Methods: This study examined the expression profiles of Smad4 in 45 samples of surgically resected pancreatic cancer. Of these 45 patients, 32 underwent pancreaticoduodenectomy. The clinicopathological parameters, the histologic features were determined and correlated to the stage at initial diagnosis, patterns of failure (locally advanced v metastatic disease) and the status SMAD4 genes. Results: Among the 45 patients, 40% of patients died with metastatic disease and 15 % died with locally advanced evolution. SMAD4 genetic status was determined in 25 patients and seems to be correlated with a high grade histologic features and progression to metastasis. Complementary data about correlation between the mutational status of SMAD4 and survival will be presented during congress. Conclusions: SMAD4 gene inactivation seems to be associated with poorer prognosis and disease progression. Prospective validation of SMAD4 as a predictive biomarker may personalize treatment strategies for patients with pancreatic cancer.

SMAD4 gene mutation and prognosis of pancreatic adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 180-180
Author(s):  
Olfa Derbel ◽  
Arnaud de la Fouchardière ◽  
Julien Peron ◽  
Francoise Desseigne ◽  
Pierre Heudel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Chemotherapeutic Agents ◽  
Clinicopathological Parameters ◽  
Molecular Heterogeneity ◽  
Smad4 Gene ◽  
Mutational Status ◽  
Smad4 Expression

180 Background: Pancreatic adenocarcinoma remains resistant to many key cytotoxic chemotherapeutic agents and novel targeted therapies. The molecular heterogeneity of this cancer may account for therapy failures to date, although the growing arsenal of novel targeted agents could translate into patient survival. A better understanding of the cellular and molecular features of advanced disease will afford new opportunities for investigation, therapeutic intervention and clinical management of patients afflicted with pancreatic cancer. Methods: Data of 46 patients with pancreatic adenocarcinoma were analyzed. The clinicopathological parameters, the histologic features were determined and correlated to the stage at initial diagnosis and patterns of failure (locally advanced v metastatic disease). Using tissue microarray, we assessed the relationship of SMAD4 expression with the overall survival of patients. Results: Among the 46 treated patients, 32 underwent pancreaticoduodenectomy. 40% of patients died with metastatic disease and 15 % died with locally advance evolution. Loss of SMAD4 expression was found in 22% of patients and seems to be correlated with a high grade histologic features and progression to metastasis disease. Complementary data about correlation between the mutational status of SMAD4 and survival will be presented during congress. Conclusions: SMAD4 gene inactivation seems to be associated with poorer prognosis and disease progression. Prospective validation of SMAD4 as a predictive biomarker may personalize treatment strategies for patients with pancreatic cancer.

Utility of PET/CT as initial staging work up for early pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 183-183
Author(s):  
Gopi Kesaria Prithviraj ◽  
Nishi Kothari ◽  
Binglin Yue ◽  
Jongphil Kim ◽  
Gregory M. Springett ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Ct Scan ◽  
Metastatic Disease ◽  
Treatment Plan ◽  
Borderline Resectable ◽  
Pet Ct ◽  
Borderline Pancreatic Cancer ◽  
Work Up ◽  
Pet Ct Scan ◽  
Initial Staging

183 Background: In pancreatic cancer, early detection and complete surgical resection with negative margins offers the only cure for the disease. Work up to evaluate resectability includes triple phase helical scan CT of the pancreas and endoscopic ultrasound (EUS). A paucity of data exists in using PET/CT scan as staging work up in early resectable pancreatic cancer. The objective of our study was to determine if PET/CT prevents futile laparotomy by detecting occult metastatic disease in patients with resectable/borderline pancreatic cancer. Methods: We looked at our institutional PET/CT data base incorporating National Oncologic PET Registry (NOPR) with diagnosis of resectable or borderline pancreatic cancer from 2005-2012. Clinical, radiographic, and pathologic follow-up was evaluated, including age, gender, evidence of metastatic disease, and initial CA 19–9 levels. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. The confidence interval was computed using the exact binomial distribution. The effect on the change was evaluated by the multiple logistic regression model. The final model was selected using the backward elimination method. Results: 287 patients with early stage (resectable or borderline) pancreatic cancer who received PET/CT as part of initial staging workup were identified. Upon initial work up (CT + EUS), 62% of patients were considered resectable and 38% were borderline resectable. However, PET/CT findings changed the management in 11.9% (n=34) of patients (95% CI: 0.084 – 0.162). 33 patients were upstaged to stage IV and 1 patient was upstaged to stage III. Median time from CT to PET/CT was 5 days. Metastatic lesions were confirmed with biopsy in 21 patients. The proportion in the change in treatment plan is significantly higher in patients who were borderline resectable (p=0.005; OR=2.94; 95% CI: 1.38 – 6.26). In 204 patients who were taken to surgery, 17.7% (n=36) were found to have metastatic disease intraoperatively. Conclusions: PET/CT helped improve detection of occult metastases, ultimately sparing these patients a potentially unnecessary operation. The role of PET/CT scan should be validated in prospective study.

Dosing modifications to increase tolerability of gemcitabine and nab-paclitaxel in treatment of pancreatic cancer in the elderly.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 441-441 ◽  
Author(s):  
Jasmine L Martin ◽  
Simran Sidhu ◽  
Nabil Benhayoun ◽  
Michael Dedonno ◽  
Warren S. Brenner
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Metastatic Disease ◽  
Drug Combination ◽  
Elderly Population ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Free Survival ◽  
Dose Reductions

441 Background: Gemcitabine and nab-paclitaxel has been reported to prolong survival in patients with metastatic pancreatic cancer. This drug combination was studied in such patients in the MPACT trial with an average age of enrolled patients being 63. Pancreatic cancer, however, is a disease of the aging with a median age at diagnosis of 70. Reductions in dosing by 20% or more in one or both components and has been shown to improve the tolerability of this regimen, thereby increasing treatment exposure. Our study aims to examine the efficacy and tolerability of this drug combination in an elderly population and how this is affected by schedule and dosing modifications. Methods: A retrospective chart review was performed of 83 patients over the age of 70 with a median age of 79 who received this drug combination as first-line treatment for pancreatic adenocarcinoma at a single institution. Overall survival and progression-free survival were assessed as well as schedule modification, dose reduction, and rates of adverse events. Results: For patients with metastatic or non-metastatic disease, the mean overall survival and progression-free survival were found to be 10.57 months and 6.63 months, respectively. When only patients with metastatic disease are analyzed, these values were found to be 9.26 months and 6.05 months, respectively, which are similar to those observed in the MPACT trial. The most common adverse events of grade 3 or greater were fatigue in 34.9% of patients and hematologic adverse events including neutropenia in 27.7% and leukopenia in 25.3% of patients. Dose reductions were commonly used to mitigate adverse events. Reductions in either one or both drugs by at least 20% occurred in 84.3% of patients. Conclusions: Gemcitabine and nab-paclitaxel in treatment of pancreatic cancer is well tolerated in an elderly population with similar rates of adverse effects when compared with previous studies, though this population experienced a significantly higher rate of fatigue. Dose reductions were used frequently in this population to improve tolerability, which may have contributed to the observed increase in overall survival in this population.

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