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Background: Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear. Method: This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells. Results: One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan–Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels. Conclusion: ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients. [ABSTRACT FROM AUTHOR]

The analysis of the main factors of brittleness is an important basis for the selection of engineering desserts in shale oil reservoirs. In this study, with the shale oil reservoir of the Liushagang Formation in the X Depression of the Beibuwan Basin as the research object, a characterization and analysis of the main factors of brittleness of the reservoir was performed in order to further reveal the brittleness of shale reservoirs in the study area. The brittleness of reservoirs in the study area was controlled by both internal and external factors, and the main factors of brittleness in the target section included the maturity of organic matter, horizontal stress difference, and brittle minerals. As the maturity of organic matter increased, the density, elastic modulus, and hardness of casein increased and the differentially hardened internal structure occurred and significantly affected brittleness. The mineral composition of the reservoir was characterized by complex mineral types and high contents of brittle minerals, and the minerals determining brittleness were mainly quartz, feldspar, calcite, and dolomite. The horizontal stress difference of the shale oil section was relatively small and contributed to fracturing and reforming. This study clarified the brittleness characteristics of E2l shale and its main factors, and provided a basis for the selection of shale formation geo-engineering dessert layers in the study area. [ABSTRACT FROM AUTHOR]

Background. NKG2A (KLRC1) belongs to the NKG2 family, which has been shown to affect the activity of natural killer (NK) cells and CD8T cells. However, a comprehensive biological analysis and exploration of NKG2A in different cancers is lacking and this needs to be further investigated. Methods. A comprehensive pan-cancer analysis of NKG2A was performed based on multiple databases. The Cancer Genome Atlas (TCGA) and Genotype–Tissue Expression (GTEx) databases were used to analyze the expression profile of NKG2A in pan-cancer. The relevance of NKG2A to the prognosis of different cancers was assessed using Kaplan–Meier survival analysis. In addition, we explored the correlation between NKG2A expression and gene mutations, pathological staging, tumor-infiltrating immune cells (TIICs), DNA methyltransferase (DNMT) genes, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and immune checkpoints (ICPs). Finally, the expression levels of NKG2A in several cancer cell lines were verified by qRT-PCR. Results. Pan-cancer comprehensive analysis showed that NKG2A expression levels were significantly different between multiple cancers and corresponding normal tissues. The differential expression of NKG2A was related to the prognosis and pathological staging of patients with multiple cancers, and was closely related to the excessive infiltration of immune cells and the regulation of ICP genes in the tumor microenvironment (TME). In addition, TMB, MSI, MMR, and DNMT genes in many cancer types are also affected by NKG2A expression. Gene set enrichment analysis (GSEA) showed that NKG2A was associated with multiple immune-related functions and pathways in malignant tumors. qRT-PCR results showed that NKG2A was underexpressed in liver, gastric, and colon cancer cell lines compared to normal cells, which was consistent with bioinformatics analysis. Conclusion. The present study suggests that NKG2A may be a potential predictive biomarker for cancer immune response and prognosis. [ABSTRACT FROM AUTHOR]

Background: The immunological checkpoint known as Inducible T Cell Costimulatory Factor (ICOS, Cluster of Differentiation, CD278) is activated and expressed on T cells. Both somatic cells and antigen-presenting cells expressed its ligand, ICOSL (including tumor cells in the tumor microenvironment).It is important for immunosuppression. Uncertainty surrounds the function of ICOS in tumor immunity. Methods: Several bioinformatics techniques were employed by us to thoroughly examine the expression and prognostic value of ICOS in 33 cancers based on data collected from TCGA and GTEx. In addition, ICOS was explored with pathological stage, tumor-infiltrating cells, immune checkpoint genes, mismatch repair (MMR) genes, DNA methyltransferases (DNMTs), microsatellite instability (MSI),and tumor mutation burden (TMB).In addition,To ascertain the level of ICOS expression in various cells, qRT-PCR was employed. Results: The findings revealed that ICOS expression was up regulation in most cancer types. The high expression of ICOS in tumor samples was related to the poor prognosis of UVM and LGG; The positive prognosis was boosted by the strong expression of ICOS in OV, SARC, SKCM, THYM, UCEC, and HNSC. The result is that the expression of malignancy was revealed by the immune cells' invasion.profile of ICOS in different types of cancer. Different ways that ICOS expression is connected to immune cell infiltration account for variations in patient survival. Additionally, the TMB, MSI, MMR, and DNMT genes as well as ICOS expression are linked in many cancer types.The results of PCR showed that it is highly expressed in gastric, breast, liver and renal cell carcinoma cell lines compared with normal cells. Conclusion: This study suggests that ICOS may be a potential tumor immunotherapy target and prognostic marker. [ABSTRACT FROM AUTHOR]

Melanoma has a high degree of central nervous system tropism, and there are many treatment modalities for melanoma brain metastases (MBM). The efficacy and toxicity of various treatments are still controversial. Therefore, they were evaluated by direct and indirect comparison to assist clinical decision-making in this study. A total of 7 therapeutic modalities for MBM were studied. Retrieval was conducted through Embase, PubMed, Cochrane Library and Web of science databases and the quality of the included literature was evaluated. Meta-analysis and Bayesian network meta-analysis were performed using Review Manager and R language. A total of 10 articles were included with 836 MBM patients. Direct comparison showed that stereotactic radiotherapy combined with immunotherapy (SRS + IT) was superior to IT (HR = 0.66, 95%CI = 0.52–0.84) or SRS (HR = 0.81, 95%CI = 0.63–1.03) alone in improving intracranial progression-free survival (PFS). In terms of overall survival (OS), SRS + IT was superior to SRS alone (HR = 0.64, 95%CI = 0.49–0.83), or IT (HR = 0.59, 95%CI = 0.29–1.21). Rank probability and surface under the cumulative ranking curve (SUCRA) by indirect comparison showed that SRS + IT had the best effect on improving intracranial PFS (0.88) and OS (0.98). Additionally, various combination therapies, especially SRS + IT (0.72), increased the incidence of radiation necrosis (RN). In direct comparisons, SRS + IT (RR = 0.93, 95%CI = 0.47–1.83) and SRS + TT (targeted therapy) (RR = 0.24, 95%CI = 0.10–0.56) did not increase intracranial hemorrhage (ICH) compared with SRS. SRS + IT treatment was the best choice for MBM patients in both intracranial PFS and OS, even though it also led to an increased probability of RN. [Display omitted] • Melanoma has a high central nervous system convergence, and the vast majority of patients develop brain metastases. • 836 patients with melanoma brain metastases were included from 10 retrospective studies. • Bayesian network meta-analysis were used to compare seven treatment modalities for melanoma brain metastases. • Stereotactic radiotherapy combined with immunotherapy has the best efficacy for melanoma brain metastases. [ABSTRACT FROM AUTHOR]