Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion.

Analysis of cuproptosis-related lncRNA signature for predicting prognosis and tumor immune microenvironment in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making.

Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma.

To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver.

ADAMTS12 promotes migration and epithelial-mesenchymal transition and predicts poor prognosis for pancreatic cancer.

Background: ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma (PDAC).

IRAK2-NF-κB signaling promotes glycolysis-dependent tumor growth in pancreatic cancer.

Background: Metabolic reprogramming has emerged as a core hallmark of cancer, and cancer metabolism has long been equated with aerobic glycolysis. Moreover, hypoxia and the hypovascular tumor microenvironment (TME) are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is imperative for tumor cell survival and proliferation. Here, we explored the impact of interleukin 1 receptor-associated kinase 2 (IRAK2) on the biological behavior of PDAC and investigated the underlying mechanism.

SF3B1 mutation in pancreatic cancer contributes to aerobic glycolysis and tumor growth through a PP2A-c-Myc axis.

Hot spot gene mutations in splicing factor 3b subunit 1 (SF3B1) are observed in many types of cancer and create abundant aberrant mRNA splicing, which is profoundly implicated in tumorigenesis. Here, we identified that the SF3B1 K700E (SF3B1 ) mutation is strongly associated with tumor growth in pancreatic ductal adenocarcinoma (PDAC). Knockdown of SF3B1 significantly retarded cell proliferation and tumor growth in a cell line (Panc05.

CD74 promotes perineural invasion of cancer cells and mediates neuroplasticity via the AKT/EGR-1/GDNF axis in pancreatic ductal adenocarcinoma.

Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC) and is one of the important causes of local recurrence in resected pancreatic cancer, but the molecular mechanism remains largely unexplored. Here, we used immunohistochemistry staining to determine the expression of CD74. Then the in vivo PNI model, in vitro neuroplasticity assay, cell proliferation assay, wound healing and Transwell-based invasion assay were performed to examine the function of CD74 in pancreatic cancer cell lines.

Single-cell RNA sequencing reveals that targeting HSP90 suppresses PDAC progression by restraining mitochondrial bioenergetics.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC.

Identification of a subset of immunosuppressive P2RX1-negative neutrophils in pancreatic cancer liver metastasis.

The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown.

Perineural Invasion Reprograms the Immune Microenvironment through Cholinergic Signaling in Pancreatic Ductal Adenocarcinoma.

Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed.

Clinical significance of programmed death 1/programmed death ligand 1 pathway in gastric neuroendocrine carcinomas.

Background: Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas (G-NECs) remains unknown.

Aim: To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.

CD90 highly expressed population harbors a stemness signature and creates an immunosuppressive niche in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with no effective treatment. Cancer cells, especially cancer stem cells (CSCs), redirect immune cells to evade immune surveillance and even coopt these immune cells to support their growth and metastasis. However, the identification of CSCs and how CSCs interact with immune cells in PDAC remain uncharacterized.

SFRP4 is a prognostic marker and correlated with Treg cell infiltration in pancreatic ductal adenocarcinoma.

Secreted Frizzled-Related Protein 4 (SFRP4), a member of secreted frizzled-related protein family, has been found as a vital modulator in cell proliferation, cell self-renew and apoptosis through Wnt signaling transduction pathway. In the present study, we re-analyzed the expression pattern of SFRPs in Gene Expression Omnibus (GEO) datasets and evaluated the expression of SFRP4 at protein level in both Kras; Trp53; Pdx1-Cre; (KPC) mice and human pancreatic ductal adenocarcinoma (PDAC) tissue. We found that the expression of SFRP4 increased gradually in PanINs and PDAC lesions in KPC mice and high expression of SFRP4 was much more common in tumor lesions compared to the adjacent non-tumor tissues.

High expression of WNT7A predicts poor prognosis and promote tumor metastasis in pancreatic ductal adenocarcinoma.

Due to the therapy resistance and frequent metastasis, pancreatic ductal adenocarcinoma(PDAC) remains one of the most malignant carcinoma. WNT7A, an important ligand of Wnt/β-catenin signaling pathways, has a controversial role in tumor development. The role of WNT7A in PDAC remains unclear.

Aberrant upregulation of KLK10 promotes metastasis via enhancement of EMT and FAK/SRC/ERK axis in PDAC.

Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors.

IL22RA1/STAT3 Signaling Promotes Stemness and Tumorigenicity in Pancreatic Cancer.

Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cells or immune cell-related signals affect pancreatic cancer stemness and development. Our previous work showed that IL22/IL22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating cross-talk between immune cells and acinar cells or stellate cells, respectively. Here, we find IL22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of patients with pancreatic cancer.

The role of Dickkopf-1 as a potential prognostic marker in pancreatic ductal adenocarcinoma.

Dickkopf-1(DKK-1), the downstream target of β-catenin/T-cell factor, participates in a negative feedback loop in the Wnt signaling and reported as an important biomarker in many tumors. In this study, we analyzed the expression of DKK-1 in pancreatic ductal adenocarcinoma (PDAC) patients at both mRNA and protein levels. We used real-time PCR to detect the expression of DKK-1 in 32 PDAC and paired adjacent non-tumor tissues, results suggested that the expression of DKK-1 was increased in PDAC tissues.

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

Background & Aims: Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.

Elevated expression of CTHRC1 predicts unfavorable prognosis in patients with pancreatic ductal adenocarcinoma.

Collagen triple helix repeat containing-1 (CTHRC1), a secreted protein, has been demonstrated as an oncogene in many types of human cancers including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the prognostic value of CTHRC1 in PDAC. In current study, we investigated the expression pattern and underlying clinical significance of CTHRC1 in PDAC.

Analysis of long non-coding RNA expression profiles in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been implicated in cancer biogenesis and prognosis. By repurposing microarray probes, we herein analysed the lncRNA expression profiles in two public PDAC microarray datasets and identified 34 dysregulated lncRNAs in PDAC.

Efficacy of Neo-Adjuvant Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma: A PRISMA-Compliant Meta-Analysis and Systematic Review.

We have conducted a meta-analysis and systematic review to determine the overall survival, mortality rate, and complete resection rate of neo-adjuvant chemoradiotherapy (CRT) compared with pancreaticoduodenectomy alone in patients with pancreatic adenocarcinoma. Whether neo-adjuvant CRT is beneficial in the treatment of resectable pancreatic cancer or not, it is still a controversial issue. Medline and Cochrane were searched with relevant terms.

Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer.

Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein associated with vascular morphogenesis and remodeling, is commonly upregulated in multiple types of human cancers and correlates with tumor progression. However, its expression pattern and underlying cellular functions in pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. In current study, we observed that expression of EDIL3 was significantly up-regulated in PDAC compared with normal controls in both cell lines and clinical specimens.

High expression of WISP-1 correlates with poor prognosis in pancreatic ductal adenocarcinoma.

WNT1 inducible signaling pathway protein 1 (WISP-1) is a member of the CCN family of growth factors and reported to possess an important role in tumorigenesis by triggering downstream events via integrin signaling. However, the exact role of WISP-1 in cancer remains unclear. In this study, we examined the expression pattern of WISP-1 at both mRNA and protein levels and evaluated the prognostic value of WISP-1 in pancreatic ductal adenocarcinoma (PDA).