Pancreatic adenosquamous carcinoma (PASC) is a rare pathological subtype of pancreatic cancer (PC), with a worse prognosis than pancreatic ductal adenocarcinoma (PDAC). Due to its rarity, our knowledge of PASC and its biological characteristics are limited. In this review, we provide an overview of the histogenesis, genetic features, diagnosis, treatment, and prognosis of PASC, as well as pancreatic squamous cell carcinoma (PSCC). The information provided here may help to clarify our understanding of PASC and provide useful avenues for further research on this disease.

The tumor microenvironment (TME) plays a vital role in the development, progression, and metastasis of pancreatic cancer (PC). The composition of the TME and its potential prognostic value remains to be fully understood, especially in adenosquamous carcinoma of pancreas (ASCP) patients. Immunohistochemistry was used to explore the clinical significance of CD3, CD4, CD8, FoxP3, and PD-L1 expression within the TME and to identify correlations with the prognosis of PC in a series of 29 patients with ASCP and 54 patients with pancreatic ductal adenocarcinoma (PDAC). Data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) were accessed to obtain the scRNA-seq data and transcriptome profiles. Seurat was used to process the scRNA-seq data, and CellChat was used to analyze cell–cell communication. CIBERSORT was used to approximate the constitution of tumor-infiltrating immune cell (TICs) profiles. Higher levels of PD-L1 were linked with a shorter overall survival in ASCP (p = 0.0007) and PDAC (p = 0.0594). A higher expression of CD3+ and CD8+ T-cell infiltration was significantly correlated with a better prognosis in PC. By influencing the composition of tumor-infiltrating immune cells (TICs), high levels of PD-L1 expression are linked with a shorter overall survival in ASCP and PDAC.

WD repeat and HMG-box DNA binding protein 1 (WDHD1) is a highly conserved gene from yeast to humans. It actively participates in DNA replication, playing a crucial role in DNA damage repair and the cell cycle, contributing to centromere formation and sister chromosome segregation. Notably, several studies have implicated WDHD1 in the development and progression of diverse tumor types, including esophageal carcinoma, pulmonary carcinoma, and breast carcinoma. Additionally, the inhibitor of WDHD1 has been found to enhance radiation sensitivity, improve drug resistance, and significantly decrease tumor cell proliferation. This comprehensive review aims to provide an overview of the molecular structure, biological functions, and regulatory mechanisms of WDHD1 in tumors, thereby establishing a foundation for future investigations and potential clinical applications of WDHD1.

Background: As a member of the Krüppel-like factor (KLFs) family, Krüppel-like factor 6 (KLF6) plays a critical role in regulating key cellular functions. Presently, scholars have proved the important role of KLF6 in the tumorigenesis of certain cancers through a large number of experiments. However, gaps still remain in our knowledge of the role of KLF6 in pancreatic cancer (PAAD). Therefore, this paper mainly investigates the role of KLF6 in the progression of pancreatic cancer. Methods: The expression pattern of KLF6 in pancreatic cancer was explored in pancreatic cancer tissues and cell lines. Then, we investigated the prognostic value of KLF6 in pancreatic cancer by immunohistochemical assays. Next, Cell Counting Kit-8 (CCK8) and clone information assays were employed to explore the proliferation of PAAD affected by KLF6. The metastasis and epithelial-mesenchymal transition (EMT) abilities affected by KLF6 were identified through transwell invasion as well as migration assays and western blots. Finally, the TRRUST tool was used to analyze the potential targeted genes of KLF6. The results were verified by Quantificational Real-time Polymerase Chain Reaction (qRT-PCR), western blot and rescue assays. Results: KLF6 expresses lowly in pancreatic cancer compared to corresponding normal tissues and relates to poor survival times. Overexpression of KLF6 inhibits the proliferation, metastasis, and EMT progression in pancreatic cancer cells. Further studies suggest that KLF6 could upregulate ATF3 in PAAD. Conclusions: Our results suggest that KLF6 can be a useful factor in predicting the prognosis of PAAD patients and that it inhibits the progression of pancreatic cancer by upregulating activating transcription factor 3 (ATF3).

Background: Nardilysin, (N-arginine dibasic convertase, NRDC) has been reported to play an important role in cancer progression, and is associated with tumor proliferation signals and inflammatory signals, such as tumor necrosis factor-a (TNF-a) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), through the activation of disintegrin and metalloproteinase (ADAM) proteases. NRDC has recently been revealed to be involved in the tumorigenesis of various types of cancer, including intrahepatic cholangiocarcinoma, malignant cerebral infarction, esophageal squamous cell carcinoma, and gastric cancer. However, the expression profiles and biological relevance of NRDC in pancreatic ductal adenocarcinoma have rarely been reported. Methods: We analyzed the NRDC expression profile in pancreatic ductal adenocarcinoma by enzyme-linked immunosorbent assay (ELISA) and identified NRDC as a circulating biomarker in the serum of 112 pancreatic ductal adenocarcinoma patients. The diagnostic value of NRDC was analyzed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test. Results: Our results demonstrated that the clinical prognosis significance of NRDC with the clinical characteristics in pancreatic ductal adenocarcinoma (PDAC). NRDC was notably decreased in PDAC patient serum compared with the control group (p < 0.001). Furthermore, the present study found that the NRDC expression level was correlated with T grade (p < 0.001), metastasis(p < 0.001), differentiation(p < 0.001), and TNM stage (p = 0.011). Further bioinformatics analysis revealed that NRDC correlated with proliferation and migration pathways; in particular, it mediated cell-matrix adhesion-dependent activation in pancreatic ductal adenocarcinoma. Conclusions: Serum NRDC may play a useful diagnostic biomarker to evaluate the aggressive clinical features in PAAD patients.

Triple-negative breast cancer (TNBC) is a type of breast tumor that currently lacks options for targeted therapy. Tremendous effort has been made to identify treatment targets for TNBC. Here, we report that the expression level of anaphase promoting complex (APC) coactivator Cdh1 in TNBC is elevated compared to that in the adjacent healthy tissues, and high levels of Cdh1 expression are correlated with poor prognoses, suggesting that Cdh1 contributes to the progression of TNBC. Interfering with the function of Cdh1 can potentiate the cytotoxic effects of PARP inhibitors against BRCA-deficient and BRCA-proficient TNBC cells through inducing DNA damage, checkpoint activation, cell cycle arrest, and apoptosis. Further investigation reveals that Cdh1 promotes BRCA1 foci formation and prevents untangled DNA entering mitosis in response to PARP inhibition (PARPi) in TNBC cells. Collectively, these results suggest that APC/Cdh1 is a potential molecular target for PARPi-based therapies against TNBCs.