Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization.

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

Histopathology and molecular pathology confirmed a diagnosis of atypical Caroli's syndrome: a case report.

Caroli's syndrome is a congenital disease characterized by dilation of intrahepatic bile ducts and congenital hepatic fibrosis. It is a rare condition in clinical work. Typically, the diagnosis of this disease is confirmed through medical imaging. Here, we report a case of atypical Caroli's syndrome in a patient who presented with recurrent upper gastrointestinal tract bleeding. The patient underwent imaging examinations, liver biopsy and whole exome sequencing. The results of the imaging examination were non-specific. However, with the aid of pathological examination, the patient was diagnosed with Caroli's syndrome. In conclusion, for cases where the imaging presentation of Caroli's syndrome is inconclusive, an accurate diagnosis should rely on pathology. By discussing this specific case, our aim is to enhance readers' understanding of this disease, provide valuable information that can aid in the early detection and appropriate management of Caroli's syndrome, ultimately improving patient outcomes.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.

An integrative bioinformatics analysis identified miR-375 as a candidate key regulator of malignant breast cancer.

MicroRNAs (miRNAs) are key regulators that play important biological roles in carcinogenesis and are promising biomarkers for cancer diagnosis and therapy. hsa-miR-375-3p (miR-375) has been suggested to serve as a tumor suppressor or oncogene in various tumor types; however, its specific expression and potential regulatory role in malignant breast cancer remain unclear. In this study, the results from noncoding RNA microarray analysis indicated that the miR-375 expression level is significantly decreased in malignant basal-like breast cancer compared with luminal-like breast cancer. A total of 1895 co-downregulated and 1645 co-upregulated genes were identified in miR-375 mimic-transfected basal-like breast cancer cell lines. Predicted miR-375 targets were obtained from the online databases TargetScan and DIANA-microT-CDS. Combined KEGG enrichment analysis for coregulated genes and predicted miR-375 targets provided information and revealed differences in potential dynamic signaling pathways regulated by miR-375 and also indicated specific regulatory pathways, such as RNA transport and processing, in basal-like breast cancer. Additionally, gene expression microarray analysis accompanied by UALCAN analysis was performed to screen upregulated genes in the basal-like subtype. Four potential key genes, including LDHB, CPNE8, QKI, and EIF5A2, were identified as candidate target genes of miR-375. Therefore, the present study demonstrated that miR-375 may be a potential key regulator and provide a promising direction for diagnostic and therapeutic developments for malignant breast cancer.

Targeting TDO in cancer immunotherapy.

Tryptophan-2,3-dioxygenase (TDO) is a homotetrameric heme-containing protein catalyzing the initial step in the kynurenine pathway, which oxidates the 2,3-double bond of the indole ring in L-tryptophan and catalyzes it into kynurenine (KYN). The upregulation of TDO results in a decrease in tryptophan and the accumulation of KYN and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence demonstrates that TDO is a promising therapeutic target in the anti-tumor process. Despite its growing popularity, there are only a few reviews focusing on TDO in tumors. Hence, we herein review the biological features and regulatory mechanisms of TDO. Additionally, we focus on the role of TDO in the anti-tumor immune response in different tumors. Finally, we also provide our viewpoint regarding the future developmental directions of TDO in cancer research, especially in relation to the development and application of TDO inhibitors as novel cancer treatments.

[A noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B].

OBJECTIVE: To construct a noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B. METHODS: 275 patients with chronic hepatitis B were divided into a training group (206 cases) and a validation group (69 cases). The constituent ratios of patients in the fibrosis stages S0-S3, fibrosis stage S4 (early cirrhosis) and active cirrhosis stage were calculated according to the liver biopsy results. 30 noninvasive variables, including age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), spleen-platelet ratio index (SRPI) and age-spleen-platelet ratio index (ASPRI), were analyzed by univariate analysis and multivariate logistic regression. Variables that were significantly different between patients with and without cirrhosis were used to construct a noninvasive prediction model, and the model was then tested in the validation group. RESULTS: (1) Of the 275 patients with chronic hepatitis B, 193 (70.2%) were in the fibrosis stages S0-S3, 42 (15.3%) in fibrosis stage S4, 40 (14.5%) in active cirrhosis stage. (2) There were 23 variables that are significantly different between patients with and without cirrhosis by univariate analysis. The 23 variables were further analyzed by multivariate logistic regression, and 4 independent factors, including international normalized ratio (INR), gamma glutamyltranspeptidase (GGT), ASPRI, hepatitis B e antigen (HBeAg) were used to construct a noninvasive prediction model. (3) By receiver operating characteristic curves (ROC) analysis, to discriminate patients in stages S0-S3 from patients in stage S4 and patients in active cirrhosis stage, the area under ROC (AUROC), cut-off value, sensitivity, specificity and accuracy of the model were 0.871, 0.458, 84.4%, 75.7%, and 79.7% respectively. To discriminate patients in active cirrhosis stage from patients in other stages, the AUROC, cut-off value, sensitivity, specificity and accuracy were 0.753, 0.526, 81.8%, 62.9%, and 67.4% respectively. There was no significant difference in AUROC between the training group and the validation group (P less than 0.05). CONCLUSION: INR, GGT, ASPRI and HBeAg are associated with early cirrhosis and active cirrhosis. Our model can be used to predict early cirrhosis and active cirrhosis.