Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

A novel prognostic prediction model of cuprotosis-related genes signature in hepatocellular carcinoma.

Background: Cuprotosis is a recently discovered copper-dependent cell death mechanism that relies on mitochondrial respiration. However, the role of cuprotosis-related genes (CRGs) in hepatocellular carcinoma (HCC) and their prognostic significances remain unknown. Methods: Based on the recently published CRGs, the LASSO Cox regression analysis was applied to construct a CRGs risk model using the gene expression data from the International Cancer Genome Consortium as a training set, followed by validation with datasets from The Cancer Genome Atlas and the Gene Expression Omnibus (GSE14520). Functional enrichment analysis of the CRGs was performed by single-sample gene set enrichment analysis. Results: Five of the 13 previously published CRGs were identified to be associated with prognosis in HCC. Kaplan-Meier analysis suggested that patients with high-risk scores have a shorter overall survival time than patients with low-risk scores. ROC curves indicated that the average AUC was more than 0.7, even at 4 years, and at least 0.5 at 5 years. Moreover, addition of this CRG risk score can significantly improve the efficiency of predicting overall survival compared to using traditional factors alone. Functional analysis demonstrated increased presence of Treg cells in patients with high-risk scores, suggesting a suppressed immune state in these patients. Finally, we point to the possibility that novel immunotherapies such as inhibitors of PDCD1, TIGIT, IDO1, CD274, CTLA4, and LAG3 may have potential benefits in high-risk patients. Conclusion: We constructed a better prognostic model for liver cancer by using CRGs. The CRG risk score established in this study can serve as a potentially valuable tool for predicting clinical outcome of patients with HCC.

Comprehensive analysis of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2): A potential novel pan-cancer immune checkpoint.

Tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly identified negative regulator of natural and acquired immunity that plays a critical function in maintaining immune homeostasis. Recently, CAR-NK immune cell therapy has been a focus of major research efforts as a novel cancer therapeutic strategy. TIPE2 is a potential checkpoint molecule for immune cell maturation and antitumor immunity that could be used as a novel NK cell-based immunotherapeutic approach. In this study, we explored the expression of TNFAIP8L2 across various tumor types and found that TNFAIP8L2 was highly expressed in most tumor types and correlated with prognosis. Survival analysis showed that TNFAIP8L2 expression was predictive of improved survival in cervical-squamous-cell-carcinoma (CESC), sarcoma (SARC) and skin-cutaneous-melanoma (SKCM). Conversely, TNFAIP8L2 expression predicted poorer survival in acute myeloid leukemia (LAML), lower-grade-glioma (LGG), kidney-renal-clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). Analysis of stemness features and immune cell infiltration indicated that TNFAIP8L2 was significantly associated with cancer stem cell index and increased macrophage and dendritic cell infiltration. Our data suggest that TNFAIP8L2 may be a novel immune checkpoint biomarker across different tumor types, particularly in LAML, LGG, KIRC and UVM, and may have further utility as a potential target for immunotherapy.

Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients.

Tigecycline is a broad-spectrum active intravenous antibiotic that is active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is unclear. In this study, we found that tigecycline cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT), and D-dimer. In addition, through functional studies, we found that tigecycline inhibit platelet adhesion and aggregation, and the coagulation function of patients gradually recover after discontinuation. Gene sequencing results suggested that tigecycline significantly regulate the expression of genes related to platelet function pathways and increase the incidence of single nucleotide polymorphisms and the number of alternative splices in the Chinese hamster ovary (CHO) cells treated with tigecycline. An abnormal function and low numbers of platelets are common in patients with hematological malignancies. Our study can explain the mechanism of abnormal coagulation caused by tigecycline. Additionally, doctors who apply tigecycline to cure infections in tumor patients should be warned.

Multi-omics analyses of tumor-associated immune-infiltrating cells with the novel immune checkpoint protein tyrosine phosphatase 1B (PTP1B) in extracellular matrix of brain-lower-grade-glioma (LGG) and uveal-melanoma (UVM).

Immune checkpoint inhibitors represented by PD-1 have greatly changed the way cancer is treated. In addition to PD-1, new immune checkpoints are constantly excavated to better treat cancer. Recently, protein tyrosine phosphatase 1B (PTP1B) was identified as a new immune checkpoint and played a critical role in the treatment of tumors by inhibiting the proliferation and cytotoxicity of T cells induced by tumor antigen. To explore the targeting role of PTP1B in precision tumor therapy, we deeply analyzed the expression and prognosis of PTP1B in all tumors. Survival analysis results indicated that PTP1B was highly expressed in most tumor tissues and indicated poor prognosis in acute-myeloid-leukemia (LAML), brain-lower-grade-glioma (LGG), kidney-renal clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). The methylation status of PTP1B in these four tumors exhibited hypomethylation and mutation landscape showed that PTP1B had its specific characteristics in genomic instability and heterogeneity. The homologous recombination deficiency (HRD) and loss of heterozygosity (LOH) were positive related to PTP1B expression in liver-hepatocellular-carcinoma (LIHC) and kidney-chromophobe (KICH), while the immunescore and immune infiltration displayed a significant positive correlation with PTP1B expression in LGG and UVM. Drug sensitivity tests showed that the PTP1B inhibitor MSI-1436 had a sensitivity effect suppressing tumor cell viability and suggested it enhanced the efficacy of PD-1 inhibitors in cancers.

Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index.

Cancer stem cells (CSCs) are characterized by self-renewal and -differential potential as compared to common cancer cells and play an important role in the development and therapeutic resistance of liver hepatocellular carcinoma (LIHC). However, the specific pathogenesis of LIHC stem cells is still unclear, and the genes involved in the stemness of LIHC stem cells are currently unknown. In this study, we investigated novel biomarkers associated with LIHC and explored the expression characteristics of stem cell-related genes in LIHC. We found that mRNA expression-based stemness index (mRNAsi) was significantly overexpressed in liver cancer tissues. Further, mRNAsi expression in LIHC increased with the tumor pathological grade, with grade 4 tumors harboring the greatest stem cell features. Upon establishing mRNAsi scores based on mRNA expression of every gene, we found an association with poor overall survival in LIHC. Moreover, modules of interest were determined based on weighted gene co-expression network analysis (WGCNA) inclusion criteria, and three significant modules (red, green, and brown) and 21 key genes (DCN, ECM1, HAND2, PTGIS, SFRP1, SRPX, COLEC10, GRP182, ADAMTS7, CD200, CDH11, COL8A1, FAP, LZTS1, MAP1B, NAV1, NOTCH3, OLFML2A, PRR16, TMEM119, and VCAN) were identified. Functional analysis of these 21 genes demonstrated their enrichment in pathways involved in angiogenesis, negative regulation of DNA-binding transcription factor activity, apoptosis, and autophagy. Causal relationship with proteins indicated that the Wnt, Notch, and Hypoxia pathways are closely related to LIHC tumorigenesis. To our knowledge, this is the first report of a novel CSC biomarker, mRNAsi, to predict the prognosis of LIHC. Further, we identified 21 key genes through mRNA expression network analysis, which could be potential therapeutic targets to inhibit the stemness of cancer cells in LIHC.