Ferroptosis-related lncRNA pairs to predict the clinical outcome and molecular characteristics of pancreatic ductal adenocarcinoma

Brief Bioinform. 2021 Sep 22:bbab388. doi: 10.1093/bib/bbab388. Online ahead of print.ABSTRACTFerroptosis is a form of regulated cell death initiated by oxidative perturbations that can be blocked by iron chelators and lipophilic antioxidants, and ferroptosis may be the silver bullet treatment for multiple cancers, including immunotherapy- and chemotherapy-insensitive cancers such as pancreatic ductal adenocarcinoma (PDAC). Numerous studies have noted that long non-coding RNAs (lncRNAs) regulate the biological behaviour of cancer cells by binding to DNA, RNA and protein. However, few studies have reported the role of lncRNAs in ferroptosis processes and the function of ferroptosis-associated lncRNAs. The primary objective of the present study was to identify ferroptosis-related lncRNAs using bioinformatic approaches combined with experimental validation. The second objective was to construct a prognostic model to predict the overall survival of patients with PDAC. The present study identified ferroptosis-related lncRNAs using a bioinformatic approach and validated them in an independent pancreatic cancer cohort from Fudan University Shanghai Cancer Center. The lncRNA SLCO4A1-AS1 was identified as a novel molecule mediating ferroptosis resistance in vitro. A novel algorithm was used to construct a '0 or 1' matrix-based prognosis model, which showed promising diagnostic accuracy for potential clinical translation (area under the curve = 0.89 for the 2-year survival rate). Notab...
Source: Briefings in Bioinformatics - Category: Bioinformatics Authors: Source Type: research

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ConclusionsThe AGIG chemo-immunotherapy regimen has presented favorable ORR, OS, and manageable toxicities as first-line therapeutic strategy of advanced pancreatic cancer treatment. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response.Clinical Trial Registrationhttps://clinicaltrials.gov/. identifier NCT03768687.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Oncol Lett. 2021 Nov;22(5):809. doi: 10.3892/ol.2021.13070. Epub 2021 Sep 27.ABSTRACTPancreatic cancer has a dire prognosis and will represent the second leading cause of cancer death in the next 10 years. The multifactorial approach represents one of the main issues in controlling the extension of this neoplasm. In recent years, the characteristics of the tumor microenvironment, metastasis mechanisms and the relationship between immune system and neoplastic cells have been described, which has made it possible to understand the pathophysiology of pancreatic adenocarcinoma. Currently, there is a failure to provide an effec...
Source: Oncology Letters - Category: Cancer & Oncology Authors: Source Type: research
Brief Bioinform. 2021 Sep 22:bbab388. doi: 10.1093/bib/bbab388. Online ahead of print.ABSTRACTFerroptosis is a form of regulated cell death initiated by oxidative perturbations that can be blocked by iron chelators and lipophilic antioxidants, and ferroptosis may be the silver bullet treatment for multiple cancers, including immunotherapy- and chemotherapy-insensitive cancers such as pancreatic ductal adenocarcinoma (PDAC). Numerous studies have noted that long non-coding RNAs (lncRNAs) regulate the biological behaviour of cancer cells by binding to DNA, RNA and protein. However, few studies have reported the role of lncRN...
Source: Briefings in Bioinformatics - Category: Bioinformatics Authors: Source Type: research
Michele Ghidini Pancreatic ductal adenocarcinoma (PDAC) has an aggressive tumor biology and is associated with poor survival outcomes. Most patients present with metastatic or locally advanced disease. In the 10–20% of patients with upfront resectable disease, surgery offers the only chance of cure, with the addition of adjuvant chemotherapy representing an established standard of care for improving outcomes. Despite resection followed by adjuvant chemotherapy, at best, 3-year survival reaches 63.4%. Post-operative complications and poor performance mean that around 50% of the patients do not commence adjuvant ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPancreas ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the USA. While other cancers with historically poor prognoses have benefited from new immunotherapies and targeted agents, the 5-year survival rate for PDAC patients has remained static. The accessibility to genomic testing has improved in recent years, and it is now clear that PDAC is a heterogenous disease, with a subset of patients harboring actionable mutations. There are several targeted therapies approved by the Food and Drug administration (FDA) in PDAC: EGFR inhibitor erlotinib (combined with gemcitabine) in unselected p...
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research
ad G. McNamara Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micr...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
This study investigates the effect of 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX), and gemcitabine plus nab-paclitaxel (GEMnPAC) regimens on PD-L1 mRNA expression in plasma-derived microvesicles (MVs) in 50 PDAC patients. Plasma was collected before starting chemotherapy and after 3 months of treatment. mRNA was extracted from MVs, and PD-L1 expression was measured by digital droplet PCR. Twenty-eight patients were PD-L1 positive in MVs at baseline, of which 18 were in the GEMnPAC cohort and 10 in the FOLFIRINOX one. The amount of PD-L1 expression in MVs increased from baseline to 3 months of treatment ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Front Oncol. 2021 Jul 5;11:682217. doi: 10.3389/fonc.2021.682217. eCollection 2021.ABSTRACTThe stroma-rich, immunosuppressive microenvironment is a hallmark of pancreatic ductal adenocarcinoma (PDA). Tumor cells and other cellular components of the tumor microenvironment, such as cancer associated fibroblasts, CD4+ T cells and myeloid cells, are linked by a web of interactions. Their crosstalk not only results in immune evasion of PDA, but also contributes to pancreatic cancer cell plasticity, invasiveness, metastasis, chemo-resistance, immunotherapy-resistance and radiotherapy-resistance. In this review, we characterize s...
Source: Ann Oncol - Category: Cancer & Oncology Authors: Source Type: research
. Pereira Many cancer studies now recognize that disease initiation, progression, and response to treatment are strongly influenced by the microenvironmental niche. Widespread desmoplasia, or fibrosis, is fundamental to pancreatic cancer development, growth, metastasis, and treatment resistance. This fibrotic landscape is largely regulated by cancer-associated fibroblasts (CAFs), which deposit and remodel extracellular matrix (ECM) in the tumor microenvironment (TME). This review will explore the prognostic and functional value of the stromal compartment in predicting outcomes and clinical prognosis in pancreatic ducta...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
The stroma-rich, immunosuppressive microenvironment is a hallmark of pancreatic ductal adenocarcinoma (PDA). Tumor cells and other cellular components of the tumor microenvironment, such as cancer associated fibroblasts, CD4+ T cells and myeloid cells, are linked by a web of interactions. Their crosstalk not only results in immune evasion of PDA, but also contributes to pancreatic cancer cell plasticity, invasiveness, metastasis, chemo-resistance, immunotherapy-resistance and radiotherapy-resistance. In this review, we characterize several prevalent populations of stromal cells in the PDA microenvironment and describe how ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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