Exploring Unique Extracellular Vesicles Associated Signatures: Prognostic Insights, Immune Microenvironment Dynamics, and Therapeutic Responses in Pancreatic Adenocarcinoma.

Extracellular vesicles play an important role in the progression of pancreatic adenocarcinoma (PAAD) through the transfer of proteins, mRNAs, and long noncoding RNAs (lncRNAs). However, the intricate interplay between extracellular vesicles-related lncRNAs and the tumor microenvironment (TME) remains poorly elucidated. Consequently, our investigation aimed to delineate the association between extracellular vesicles-related lncRNAs and the PAAD microenvironment. Initially, we identified differentially expressed lncRNAs (DELs) from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project datasets. Subsequently, we validated the expression of these DELs within extracellular vesicles and assessed their prognostic implications in PAAD using the GSE133684 and TCGA datasets. Multiomics data were analyzed comprehensively, including genomic landscape, functional annotation, immune profiles, and therapeutic responses. Differential expression of selected lncRNAs in both cellular and exosomal fractions of PAAD was further confirmed through quantitative polymerase chain reaction (qPCR). Eight DELs were identified from TCGA and GTEx datasets, and two exosomal lncRNAs exhibited a significant correlation with overall survival, warranting further investigation. Specifically, elevated expression of LINC00996 correlated positively with immune infiltration and enhanced response to immunotherapy. Conversely, heightened expression of TRHED-AS1 was associated with compromised immune cell infiltration and diminished responsiveness to immunotherapy. Our study establishes a compelling link between two extracellular vesicles-related gene signatures, prognosis, and immune infiltration in PAAD. Notably, these signatures serve as robust prognostic indicators for PAAD patients, offering valuable insights for the strategic selection of immunotherapeutic interventions.

Nan K ，Zhang M ，Geng Z ，Zhang Y ，Liu L ，Yang Z ，Xu P ... -  《-》

Development and validation of a novel N6-methyladenosine (m6A)-related multi- long non-coding RNA (lncRNA) prognostic signature in pancreatic adenocarcinoma.

Yuan Q ，Ren J ，Li L ，Li S ，Xiang K ，Shang D ... -  《-》

Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell.

Sun Y ，Yao L ，Man C ，Gao Z ，He R ，Fan Y ... -  《Frontiers in Immunology》

Comprehensive exploration of immune checkpoint-related genes in the prognosis and tumor immune microenvironment of pancreatic adenocarcinoma.

To comprehensively analyze the clinical significance of Immune Checkpoint-Related Genes (ICRGs) in Pancreatic Adenocarcinoma (PAAD). PAAD tissues and normal pancreatic tissues were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and 283 ICRGs were integrated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome datasets. Unsupervised clustering was used to obtain potential ICRGs-based PAAD subtypes. Wilcoxon test was performed to screen Differentially Expressed ICRGs (DEICRGs), while cox regression analyses were utilized to identify prognosis-related ICRGs and clinicopathological factors, and construct the corresponding models. The Tumor Immune Microenvironment (TIME) was evaluated. Moreover, the authors performed enrichment analysis, Gene Set Enrichment Analysis (GSEA), and transcription factor regulatory networks to realize underlying mechanisms. Three ICRGs-based PAAD subtypes were identified, and they were associated with three ESTIMATE scores, a Tumor Microenvironment (TMB) score, 14 therapeutic immune checkpoints, and infiltration levels of seven immune cells. On top of that, the authors constructed two signatures based on DEICRGs to predict the Overall Survival (OS) (Area Under the ROC Curve [AUC: 0.741∼0.778]) and Progression-Free Survival (PFS) (AUC: 0.746∼0.831) of patients. Two nomograms were established by combining clinical variables and signatures. In addition, the authors found higher infiltration of naïve B cells and CD8+ T-cells in low-risk PAAD patients, and higher infiltration of suppressive immune cells and cancer-related signaling pathways in high-risk PAAD patients. The present study suggested that ICRGs were associated with TIME formation and prognosis of PAAD patients, which may serve as novel clinical biomarkers and therapeutic targets.

Chen X ，Zhang H 《-》

Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer.

Guo Y ，Wang R ，Li J ，Song Y ，Min J ，Zhao T ，Hua L ，Shi J ，Zhang C ，Ma P ，Yang C ，Zhu L ，Gan D ，Li S ，Liu X ，Su H ... -  《Frontiers in Immunology》