scholarly journals A novel lncRNA PTTG3P/miR-132/212-3p/FoxM1 feedback loop facilitates tumorigenesis and metastasis of pancreatic cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Wenyu Liu ◽  
Jian Tang ◽  
Huiqing Zhang ◽  
Fanyang Kong ◽  
Huiyun Zhu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Experimental Evidence ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Size ◽  
Pituitary Tumor ◽  
Feedback Loop ◽  
Diagnostic Marker ◽  
Ductal Adenocarcinoma ◽  
Microrna Sponge

AbstractPseudogene pituitary tumor-transforming 3 (PTTG3P) is emerging as a key player in the development and progression of cancer. However, the biological role and clinical significance of PTTG3P in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we found that PTTG3P was significantly upregulated in PDAC tissues. Elevated PTTG3P expression correlated with larger tumor size and worse differentiation, and reduced overall survival. Bioinformatics and experimental evidence revealed that PTTG3P promoted malignant phenotypes and FoxM1 signaling pathway in PDAC cells. Mechanistically, PTTG3P functions as a microRNA sponge to positively regulate the expression of FoxM1 through sponging miR-132/212-3p. Moreover, it showed that FoxM1 transcriptionally activated PTTG3P expression, thus forming a feedback loop to promote the aggressiveness of PDAC cells. Taken together, our findings suggest that PTTG3P promotes PDAC progression through PTTG3P/miR-132/212-3p/FoxM1 feedforward circuitry and it may serve as a promising diagnostic marker or target for treatment in PDAC patients.

Precursors of pancreatic cancer in background of chronic opisthorchiasis

2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Morphological Data ◽  
Small Samples ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Opisthorchis Felineus ◽  
Disease Free

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.

The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

2021 ◽  
Author(s):  
Se Jun Park ◽  
Hyunho Kim ◽  
Kabsoo Shin ◽  
Tae Ho Hong ◽  
Ja Hee Suh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Real World ◽  
Median Overall Survival ◽  
Ductal Adenocarcinoma ◽  
Nanoliposomal Irinotecan ◽  
Previously Treated ◽  
Grade 3

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

Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Perioperative Morbidity ◽  
Log Rank Test ◽  
Kaplan Meier

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.

scholarly journals Meta-analysis of 1,200 transcriptomic profiles identifies a prognostic model for pancreatic ductal adenocarcinoma

2018 ◽  
Author(s):  
Vandana Sandhu ◽  
Knut Jorgen Labori ◽  
Ayelet Borgida ◽  
Ilinca Lungu ◽  
John Bartlett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Model ◽  
Meta Analysis ◽  
Early Death ◽  
Receiver Operating Curve ◽  
Ductal Adenocarcinoma ◽  
Survival Predictor

ABSTRACTBackgroundWith a dismal 8% median 5-year overall survival (OS), pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Only 10-20% of patients are eligible for surgery, and over 50% of these will die within a year of surgery. Identify molecular predictors of early death would enable the selection of PDAC patients at high risk.MethodsWe developed the Pancreatic Cancer Overall Survival Predictor (PCOSP), a prognostic model built from a unique set of 89 PDAC tumors where gene expression was profiled using both microarray and sequencing platforms. We used a meta-analysis framework based on the binary gene pair method to create gene expression barcodes robust to biases arising from heterogeneous profiling platforms and batch effects. Leveraging the largest compendium of PDAC transcriptomic datasets to date, we show that PCOSP is a robust single-sample predictor of early death (≤1 yr) after surgery in a subset of 823 samples with available transcriptomics and survival data.ResultsThe PCOSP model was strongly and significantly prognostic with a meta-estimate of the area under the receiver operating curve (AUROC) of 0.70 (P=1.9e-18) and hazard ratio (HR) of 1.95(1.6-2.3) (P=2.6e-16) for binary and survival predictions, respectively. The prognostic value of PCOSP was independent of clinicopathological parameters and molecular subtypes. Over-representation analysis of the PCOSP 2619 gene-pairs (1070 unique genes) unveiled pathways associated with Hedgehog signalling, epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) signalling.ConclusionPCOSP could improve treatment decision by identifying patients who will not benefit from standard surgery/chemotherapy and may benefit from alternate approaches.AbbreviationsAUROCArea under the receiver operating curveGOGene annotationOSOverall survivalPCOSPPancreatic cancer overall survival predictorPDACPancreatic ductal adenocarcinomaTSPTop scoring pairs.

scholarly journals Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker?

2021 ◽  
Author(s):  
Ignacio Guillermo Merlo ◽  
Victoria Ardiles ◽  
Rodrigo Sanchez-Clariá ◽  
Eugenia Fratantoni ◽  
Eduardo de Santibañes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Adjuvant Treatment ◽  
Tumor Size ◽  
Pancreatic Resection ◽  
Perineural Invasion ◽  
Undifferentiated Carcinoma ◽  
Ductal Adenocarcinoma ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

Abstract Background: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio and its variation pre and post-operatively (delta NLR) in overall survival after pancreatectomy for pancreatic ductal adenocarcinoma at a single centre and to identify factors associated with overall survival.Methods: A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between evaluated factors and overall survival were analyzed using a log-rank test and Cox proportional hazard regression model.Results: Overall, 242 patients underwent complete pancreatic resection for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% CI: 19.5-29) and survival rates at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. NLR and delta NLR were not significantly associated with survival (HR=1.14, 95%CI: 0.77-1.68, p=0.5). Lymph node ratio was significantly associated (HR=1.66, 95%CI: 1.21-2.26, p=0.001) in the bivariate analysis. In multivariable analysis the only factors that were significantly associated with survival were perineural invasion (HR=1.94, 95%CI: 1.21-3.14, p=0.006), surgical margin (HR=1.83, 95%CI: 1.10-3.02, p=0.019), tumor size (HR=1.01, 95%CI: 1.003-1.027, p=0.16), postoperative CA 19-9 level (HR=1.001, p<0.001), and completion of adjuvant treatment (HR=0.53, 95%CI: 0.35-0.8, p=0.002).Conclusion: Neutrophil-lymphocyte ratio and delta NLR were not associated with overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.

scholarly journals Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Se Jun Park ◽  
Hyunho Kim ◽  
Kabsoo Shin ◽  
Tae Ho Hong ◽  
Ja Hee Suh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Nanoliposomal Irinotecan ◽  
Previously Treated

Abstract Background According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. Methods We 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 (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. Results Fifty-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% 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 grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic 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). Conclusions Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. Trial registration Retrospectively registered.

scholarly journals Pancreatic Cancer Survival Prediction: A Survey of the State-of-the-Art

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Wilson Bakasa ◽  
Serestina Viriri
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Survival ◽  
State Of The Art ◽  
The State ◽  
Ductal Adenocarcinoma ◽  
Support Vector ◽  
Survival Prediction ◽  
Use Of Resources

Cancer early detection increases the chances of survival. Some cancer types, like pancreatic cancer, are challenging to diagnose or detect early, and the stages have a fast progression rate. This paper presents the state-of-the-art techniques used in cancer survival prediction, suggesting how these techniques can be implemented in predicting the overall survival of pancreatic ductal adenocarcinoma cancer (pdac) patients. Because of bewildering and high volumes of data, the recent studies highlight the importance of machine learning (ML) algorithms like support vector machines and convolutional neural networks. Studies predict pancreatic ductal adenocarcinoma cancer (pdac) survival is within the limits of 41.7% at one year, 8.7% at three years, and 1.9% at five years. There is no significant correlation found between the disease stages and the overall survival rate. The implementation of ML algorithms can improve our understanding of cancer progression. ML methods need an appropriate level of validation to be considered in everyday clinical practice. The objective of these techniques is to perform classification, prediction, and estimation. Accurate predictions give pathologists information on the patient’s state, surgical treatment to be done, optimal use of resources, individualized therapy, drugs to prescribe, and better patient management.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1612
Author(s):  
Julie Earl ◽  
Emma Barreto ◽  
María E. Castillo ◽  
Raquel Fuentes ◽  
Mercedes Rodríguez-Garrote ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Somatic Mutation ◽  
Disease Status ◽  
Clinical Analysis ◽  
Cytotoxic Agents ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Circulating Free Dna

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.

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