Single-cell RNA-seq reveals heterogeneity in metastatic renal cell carcinoma and effect of anti-angiogenesis therapy in the pancreas metastatic lesion.

Metastatic clear cell renal cell carcinoma has heterogenous tumor microenvironment (TME). Among the metastatic lesions, pancreas metastasis is rare and controversy in treatment approaches. Here, extensive primary and metastatic lesion samples were included by single-cell RNA-seq to decipher the distinct metastasis TME.

Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled the development of immunotherapeutic and targeted therapeutic strategies with a promising future. The emergence of single-cell sequencing and mass spectrometry technologies, coupled with spatial omics, has collectively revealed the heterogeneity of the TME from a multiomics perspective, outlined the development trajectories of cell lineages, and revealed important functions of previously underrated myeloid cells and tumor stroma cells.

FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. In this study, we identified FBXO32 as an oncogenic driver in PDAC.

Multiomics integration reveals NETosis heterogeneity and TLR2 as a prognostic biomarker in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm characterized by a poor prognosis and limited therapeutic strategy. The PDAC tumor microenvironment presents a complex heterogeneity, where neutrophils emerge as the predominant constituents of the innate immune cell population. Leveraging the power of single-cell RNA-seq, spatial RNA-seq, and multi-omics approaches, we included both published datasets and our in-house patient cohorts, elucidating the inherent heterogeneity in the formation of neutrophil extracellular traps (NETs) and revealed the correlation between NETs and immune suppression.

E3 ubiquitin ligase RBCK1 confers ferroptosis resistance in pancreatic cancer by facilitating MFN2 degradation.

Ferroptosis, a novel form of iron-dependent non-apoptotic cell death, plays an active role in the pathogenesis of diverse diseases, including cancer. However, the mechanism through which ferroptosis is regulated in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, our study, via combining bioinformatic analysis with experimental validation, showed that ferroptosis is inhibited in PDAC.

The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3.

Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2's role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis.

Ribosome profiling: a powerful tool in oncological research.

Neoplastic cells need to adapt their gene expression pattern to survive in an ever-changing or unfavorable tumor microenvironment. Protein synthesis (or mRNA translation), an essential part of gene expression, is dysregulated in cancer. The emergence of distinct translatomic technologies has revolutionized oncological studies to elucidate translational regulatory mechanisms.

Epidemiology of pancreatic cancer: New version, new vision.

Pancreatic cancer (PC) is a devastating malignancy with an extremely high mortality rate and poses significant challenges to healthcare systems worldwide. The prevalence of PC risk factors spiked over the years, leading to a global increase in PC incidence rates. The contribution of different risk factors, however, varied from region to region due to genetic predisposition, environmental, social, and political factors underlying disease prevalence in addition to public health strategies.

Novel strategies optimize immunotherapy by improving the cytotoxic function of T cells for pancreatic cancer treatment.

Pancreatic cancer (PC) is considered highly malignant due to its unsatisfying prognosis and limited response to therapies. Immunotherapy has therefore been developed to harness the antigen-specific properties and cytotoxicity of the immune system, aiming to induce a robust anti-tumor immune response that specifically demolishes PC cells while minimizing lethality in healthy tissue. The activation and augmentation of cytotoxic T cells play a critical role in the initiation and final success of immunotherapy.

From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.

Purpose: This study aims to review the multifaceted roles of a membrane protein named Fibroblast Activation Protein (FAP) expressed in tumor tissue, including its molecular functionalities, regulatory mechanisms governing its expression, prognostic significance, and its crucial role in cancer diagnosis and treatment.

Methods: Articles that have uncovered the regulatory role of FAP in tumor, as well as its potential utility within clinical realms, spanning diagnosis to therapeutic intervention has been screened for a comprehensive review.

Results: Our review reveals that FAP plays a pivotal role in solid tumor progression by undertaking a multitude of enzymatic and nonenzymatic roles within the tumor stroma.

Organoid: Bridging the gap between basic research and clinical practice.

Nowadays, the diagnosis and treatment system of malignant tumors has increasingly tended to be more precise and personalized while the existing tumor models are still unable to fully meet the needs of clinical practice. Notably, the emerging organoid platform has been proven to have huge potential in the field of basic-translational medicine, which is expected to promote a paradigm shift in personalized medicine. Here, given the unique advantages of organoid platform, we mainly explore the prominent role of organoid models in basic research and clinical practice from perspectives of tumor biology, tumorigenic microbes-host interaction, clinical decision-making, and regenerative strategy.

Comparing the clinical value of baseline [ Ga]Ga-FAPI-04 PET/CT and [F]F-FDG PET/CT in pancreatic ductal adenocarcinoma: additional prognostic value of the distal pancreatitis.

Purpose: Anatomical and molecular staging strategies are needed for the personalized treatment of localized pancreatic ductal adenocarcinoma (PDAC). This study evaluated the performance of [ Ga]Ga-FAPI-04 and [F]F-FDG PET/CT on the disease staging and prognostic value of patients with localized PDAC on contrast-enhanced (CE)-CT images.

Methods: Patients with suspected localized PDAC on CE-CT were recruited for static [ Ga]Ga-FAPI-04 and [F]F-FDG and PET/CT, and select patients underwent simultaneous 60-min dynamic  Ga-FAPI-04 PET/CT.

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Objective: Pancreatic cancer (PC) is highly malignant, but the underlying mechanisms of cancer progression remain unclear. PRKRA is involved in cellular stress response, but its role in PC was unknown.

Methods: The expression of PRKRA between normal and tumor tissues were compared, and the prognostic value of PRKRA was evaluated.

Comprehensive study of clinical features, prognostic factors, and survival in patients with pancreatic solid pseudopapillary neoplasms based on the 2019 WHO classification.

Background: Pancreatic solid pseudopapillary neoplasms (pSPNs) are a rare tumor type with a limited understanding of their clinical characteristics and survival outcomes. We aimed to investigate potential prognostic factors among the existing clinical features in patients diagnosed with pSPN.

Methods: For this study, we utilized data from the Surveillance Epidemiology and End Results (SEER) database, specifically selecting patients with a histology type of pSPN from the years 2000 to 2019.

Prognostic value of preoperative [ Ga]Ga-FAPI-04 PET/CT in patients with resectable pancreatic ductal adenocarcinoma in correlation with immunohistological characteristics.

Purpose: Our aim was to assess the prognostic value of [ Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC).

Methods: We retrospectively analyzed treatment-naïve PDAC patients who underwent preoperative [ Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUV), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUV), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF).

mTOR inhibitor, gemcitabine and PD-L1 antibody blockade combination therapy suppresses pancreatic cancer progression via metabolic reprogramming and immune microenvironment remodeling in Trp53LSL-KrasPdx-1-Cre murine models.

Objective: Resistance to immunotherapy and chemotherapy hinders the prognosis of pancreatic cancer(PC). We hypothesized that the combination of mTOR inhibitor sirolimus and gemcitabine would change the metabolic landscape of PC and enhance the anti-PD-L1 therapy.

Methods: In KPC mice, the following regimens were administered and tumor growth inhibition rates(TGI%) were calculated: sirolimus(S), PD-L1 antibody(P), gemcitabine(G), sirolimus + PD-L1 antibody(SP), sirolimus + gemcitabine(SG), PD-L1 + gemcitabine(PG) and sirolimus + PD-L1 antibody + gemcitabine(SPG).

Cancer-specific survival and metastasis in pancreatic mucinous cystadenocarcinoma: A SEER-based cohort study.

Aims: This study aimed to investigate the prognostic value of clinical features for cancer-specific survival (CSS) and metastasis in patients with pancreatic mucinous cystadenocarcinoma (MCAC). We further constructed and validated an effective nomogram to predict CSS.

Methods: We screened patients diagnosed with pancreatic MCAC from Surveillance Epidemiology and End Results (SEER) database.

Meta-analysis of robotic versus open pancreaticoduodenectomy in all patients and pancreatic cancer patients.

Purposes: To compare perioperative outcomes of robotic pancreaticoduodenectomy (RPD) to open pancreaticoduodenectomy (OPD) using evidence from cohort studies.

Methods: Outcomes of interest include operative time, blood loss, R0 resection rate, lymph nodes harvested, overall complication rate, pancreatic fistula rate, delayed gastric emptying rate and 90-day mortality.

Results: 6 prospective studies and 15 retrospective studies were included.

Identification and Validation of Constructing the Prognostic Model With Four DNA Methylation-Driven Genes in Pancreatic Cancer.

Pancreatic cancer (PC) is a highly aggressive gastrointestinal tumor and has a poor prognosis. Evaluating the prognosis validly is urgent for PC patients. In this study, we utilized the RNA-sequencing (RNA-seq) profiles and DNA methylation expression data comprehensively to develop and validate a prognostic signature in patients with PC.

A randomised, multicentre trial of somatostatin to prevent clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy.

Background: Prophylactic somatostatin to reduce the incidence of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy remains controversial. We assessed the preventive efficacy of somatostatin on clinically relevant postoperative pancreatic fistula in intermediate-risk patients who underwent pancreaticoduodenectomy at pancreatic centres in China.

Methods: In this multicentre, prospective, randomised controlled trial, we used the updated postoperative pancreatic fistula classification criteria and cases were confirmed by an independent data monitoring committee to improve comparability between centres.