Expression analysis in ductal adenocarcinoma in patients with low and high survival after tumor resection
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE84219 | GEO | 2017/10/04
SECONDARY ACCESSION(S): PRJNA328399
REPOSITORIES: GEO
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Project description:BackgroundSurgery remains the only curative option for the treatment of pancreatic adenocarcinoma (PDAC). The goal of this study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head.MethodsThe data from 195 patients who underwent pancreatic head resection for PDAC between 1993 and 2011 in our center were retrospectively analyzed. The prognostic factors for survival after operation were evaluated using multivariate analysis.ResultsThe head resection surgeries included 69.7% pylorus-preserving pancreatoduodenectomies (PPPD) and 30.3% standard Kausch-Whipple pancreatoduodenectomies (Whipple). The overall mortality after pancreatoduodenectomy (PD) was 4.1%, and the overall morbidity was 42%. The actuarial 3- and 5-year survival rates were 31.5% (95% CI, 25.04%-39.6%) and 11.86% (95% CI, 7.38%-19.0%), respectively. Univariate analyses demonstrated that elevated CEA (p = 0.002) and elevated CA 19-9 (p = 0.026) levels, tumor grade (p = 0.001) and hard texture of the pancreatic gland (p = 0.017) were significant predictors of a poor survival. However, only CEA >3 ng/ml (p < 0.005) and tumor grade 3 (p = 0.027) were validated as significant predictors of survival in multivariate analysis.ConclusionsOur results suggest that tumor marker levels and tumor grade are significant predictors of poor survival for patients with pancreatic head cancer. Furthermore, hard texture of the pancreatic gland appears to be associated with poor survival.
| S-EPMC3639824 | biostudies-literature
Project description:A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma Pancreatic ductal adenocarcinoma (PDAC), comprising over 90% of all pancreatic cancers, remains a lethal disease with an estimated 232,000 new cases, 227,000 deaths per year worldwide, and a less than 5% five-year survival rate. Currently the standard of care for the 20% of patients with localized disease is surgery followed by chemotherapy, and in some cases radiation. Unfortunately despite the use of adjuvant therapy, median survival remains at best 23 months. It is important to note however, that up to 27% of patients with resected PDAC can survive for five years. However, in these studies examining actual long-term survivors, only two have found that adjuvant therapy was associated with improved survival. In addition, randomized controlled trials of gemcitabine-based chemotherapy demonstrate an improvement in median survival of at best 3 months. One possible conclusion from these studies is that tumor biology dictates outcome and that our current adjuvant therapy has only a modest impact on altering a patient's course.Hypothesizing that the dismal outcome of patients with localized disease is due to the presence of micrometastasic disease, current clinical investigation has focused on preoperative or neoadjuvant therapy. This approach, where patients who cannot tolerate the stress of therapy or develop metastatic disease during treatment are spared surgery, has demonstrated an overall survival of 34 months in this highly selected patient population. Therefore the ability to select patients who would most benefit from a neoadjuvant approach may be important. One way to do this is to define a prognostic gene signature that can identify patients with more aggressive tumor biology upfront. reference x sample The 30 Nebraska and UNC samples were not analyzed with clinical data so it is not provided. One of the PE samples is missing some clinical data.
2010-07-18 | E-GEOD-21501 | biostudies-arrayexpress
Project description:Different clinical presentations and prognoses have been implied between pancreatic head and body/tail cancers. We aimed to identify the prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). Thirty-two pairs of patients with strictly matched early stage (II) pancreatic head and body/tail cancers were enrolled. The molecular feature of the two subtypes of PDAC was assessed on the level of miRNA expression. Out of the 64 patients, 34 (53.1%) had tumor recurrence after radical resection during the follow-up period (2.3 ± 0.8 years). Both overall and tumor-free survival were significantly higher in the patients with pancreatic body/tail cancer compared with those with pancreatic head cancer. Patient age and tumor location were the independent prognostic factors for tumor recurrence. A remarkably lower expression of miR-501-3p and higher expression of miR-375 were found and were further verified in pancreatic body/tail cancer tissues compared with pancreatic head cancer tissues. The low expression of miR-501-3p was significantly associated with a low risk of tumor recurrence. Both, subcutaneous and orthotopic PDAC mouse models presented highly invasive tumor phenotypes upon up-regulated miR-501-3p expression. An in vitro study showed that miR-501-3p promoted the invasiveness of PDAC cells possibly via suppressing E-cadherin. In summary, at resectable early stage, pancreatic body/tail cancer presents a less malignant phenotype associated with deregulation of miR-501-3p compared with pancreatic head cancer.
| S-EPMC5362475 | biostudies-literature
Project description:A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma Pancreatic ductal adenocarcinoma (PDAC), comprising over 90% of all pancreatic cancers, remains a lethal disease with an estimated 232,000 new cases, 227,000 deaths per year worldwide, and a less than 5% five-year survival rate. Currently the standard of care for the 20% of patients with localized disease is surgery followed by chemotherapy, and in some cases radiation. Unfortunately despite the use of adjuvant therapy, median survival remains at best 23 months. It is important to note however, that up to 27% of patients with resected PDAC can survive for five years. However, in these studies examining actual long-term survivors, only two have found that adjuvant therapy was associated with improved survival. In addition, randomized controlled trials of gemcitabine-based chemotherapy demonstrate an improvement in median survival of at best 3 months. One possible conclusion from these studies is that tumor biology dictates outcome and that our current adjuvant therapy has only a modest impact on altering a patient's course.Hypothesizing that the dismal outcome of patients with localized disease is due to the presence of micrometastasic disease, current clinical investigation has focused on preoperative or neoadjuvant therapy. This approach, where patients who cannot tolerate the stress of therapy or develop metastatic disease during treatment are spared surgery, has demonstrated an overall survival of 34 months in this highly selected patient population. Therefore the ability to select patients who would most benefit from a neoadjuvant approach may be important. One way to do this is to define a prognostic gene signature that can identify patients with more aggressive tumor biology upfront.
2010-07-19 | GSE21501 | GEO
Project description:BackgroundElevated plasma D-dimer levels have been reported as an unfavorable prognostic indicator in many solid tumors. However, there are limited relevant studies in pancreatic cancer patients following radical surgery, and the clinical significance remains controversial. The aim of this study was to investigate the clinical and prognostic significance of preoperative plasma D-dimer in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection.MethodsA retrospective analysis was performed on all patients who consecutively underwent radical surgery for PDAC by laparotomy or robotic surgery from December 2011 to December 2018. Baseline clinicopathologic characteristics, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to analyze the prognostic value of preoperative plasma D-dimer.ResultsAmong 1351 patients, elevated preoperative plasma D-dimer levels (≥ 0.55 ng/mL) were found in 417 (30.9%) patients. Three hundred twelve (23.09%) underwent minimally invasive robotic pancreatectomy. The median overall survival (OS) of patients with elevated D-dimer levels was 6.3 months shorter than that of patients with normal D-dimer levels (15.0 months vs 21.3 months, p < 0.001). Multivariate analysis showed that elevated D-dimer levels independently predicted poorer OS (hazard ratio, 1.33; 95% confidence interval, 1.17-1.51, p < 0.001). Subgroup analysis demonstrated that D-dimer was a reliable prognostic factor in patients who underwent R0 resection. In addition, integration of D-dimer, carbohydrate antigen 19-9 (CA19-9), and NLR provided a better prognostic model for PDAC patients before operation.ConclusionAn elevated preoperative plasma D-dimer level was a reliable independent prognostic factor for OS in patients with PDAC undergoing resection. Combination of D-dimer, CA19-9, and NLR can enhance the prognostic accuracy before operation.
| S-EPMC8191214 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma
| PRJNA432344 | ENA
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a progressive cancer with only about 12 % of a 5-year survival rate. PDAC generally shows strong chemoresistance, which has been correlated with the tumor microenvironment (TME) of PDAC consisting of various types of stromal cells. Recent single-cell RNA sequence (scRNAseq) analyses demonstrate that a high percentage of myeloid cells in TME stroma cells is related to poor prognosis, and, among myeloid cells, tumor associated macrophages (TAM) are the most abundant population. However, their functions in PDAC malignancy remain largely unknown. Previously, we established a PDAC-organoid associated with an artificial TME by co-culturing patient-derived cancer cells, human induced pluripotent stem cell (hiPSC) derived mesenchymal and endothelial cells, which is called fused pancreatic cancer organoid (FPCO). Here, we further incorporated macrophages into FPCO and named it M0-FPCO. After 1 week of organoid culture, the macrophages in M0-FPCO expressed the conventional markers of M2-macrophages, such as CD163 and CD206. However, bulk RNAseq analysis showed that macrophages in M0-FPCO (FPCO-Mac) have distinct characteristics as compared with M2-macrophages induced with IL4 and 13. scRNAseq of M0-FPCO further demonstrated that FPCO-Mac was divided into 6 populations including Granulin+-TAM and SPP1+-TAM, which had been identified in human PDAC tissue. Furthermore, the number of PDAC cells was reduced in FPCO but not in M0-FPCO between 1 and 2 weeks of organoid culture, suggesting that cancer cells could survive longer or are protected from cell death in the presence of TAM. Moreover, the bulk-RNAseq analysis of the surviving M0-FPCO unveiled a GALE potentially associated with a worse prognosis in PDAC patients. Our novel PADC organoid including macrophage (M0-FPCO) replicated the PDAC-TAM features and elucidated their protumorigenic function.
2024-12-01 | GSE249670 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a progressive cancer with only about 12 % of a 5-year survival rate. PDAC generally shows strong chemoresistance, which has been correlated with the tumor microenvironment (TME) of PDAC consisting of various types of stromal cells. Recent single-cell RNA sequence (scRNAseq) analyses demonstrate that a high percentage of myeloid cells in TME stroma cells is related to poor prognosis, and, among myeloid cells, tumor associated macrophages (TAM) are the most abundant population. However, their functions in PDAC malignancy remain largely unknown. Previously, we established a PDAC-organoid associated with an artificial TME by co-culturing patient-derived cancer cells, human induced pluripotent stem cell (hiPSC) derived mesenchymal and endothelial cells, which is called fused pancreatic cancer organoid (FPCO). Here, we further incorporated macrophages into FPCO and named it M0-FPCO. After 1 week of organoid culture, the macrophages in M0-FPCO expressed the conventional markers of M2-macrophages, such as CD163 and CD206. However, bulk RNAseq analysis showed that macrophages in M0-FPCO (FPCO-Mac) have distinct characteristics as compared with M2-macrophages induced with IL4 and 13. scRNAseq of M0-FPCO further demonstrated that FPCO-Mac was divided into 6 populations including Granulin+-TAM and SPP1+-TAM, which had been identified in human PDAC tissue. Furthermore, the number of PDAC cells was reduced in FPCO but not in M0-FPCO between 1 and 2 weeks of organoid culture, suggesting that cancer cells could survive longer or are protected from cell death in the presence of TAM. Moreover, the bulk-RNAseq analysis of the surviving M0-FPCO unveiled a GALE potentially associated with a worse prognosis in PDAC patients. Our novel PADC organoid including macrophage (M0-FPCO) replicated the PDAC-TAM features and elucidated their protumorigenic function.
2024-12-01 | GSE249672 | GEO
Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma. Methods: This is a single-institution, retrospective study based on a prospectively maintained database. Pancreatic ductal adenocarcinoma (N = 342) and periampullary adenocarcinoma patients (N = 76) who underwent pancreatic resection surgery between 2016 and 2021 were included. Immunohistochemistry staining results of MMR proteins and next-generation sequencing data were recorded. Cancer-type dependent Cox regression analyses were performed to assess overall and disease-free survival, which was complemented with a 1:2 propensity-score matching for each of the cancer types in order to compare oncologic outcomes. Results: A total of 418 pancreatic cancer patients were included in the analysis. Fifteen patients (3.5%) were diagnosed as dMMR (PDAC N = 7 and periampullary adenocarcinoma N = 8). Cox regression modeling of dMMR status interaction with TNM staging and cancer type revealed that dMMR status strongly improves overall survival (p < 0.05). After propensity-score matching, Cox regression identified dMMR status as a significant marker of improved overall survival (HR = 0.27, 95%CI 0.09-0.88, p = 0.029). Conclusions: Overall, our findings suggest that dMMR status is associated with markedly improved survival outcomes in patients after resection of pancreatic and periampullary cancer. Future large-scale studies are needed to further validate this finding.
| S-EPMC11508431 | biostudies-literature
Project description:Analysis of expression profile of peripheral blood from pancreatic ductal adenocarcinoma patients RNA expression profile of peripheral blood from pancreatic ductal adenocarcinoma patients
2015-11-04 | GSE74629 | GEO