Anoikis-related genes in breast cancer patients: reliable biomarker of prognosis.

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.

Potential role of lncRNA LOXL1-AS1 in human cancer development: a narrative review.

Background and Objective: Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs consisting of more than 200 nucleotides that are widely involved in various physiological and pathobiological processes in the body. LncRNA plays a crucial role in tumorigenesis and development with its unique functions, such as playing a role in a variety of biological processes of malignant tumors as a cancer-promoting factor or a cancer-suppressor factor. Lysyl oxidase-like protein 1-antisense RNA1 (LOXL1-AS1) is a novel functional lncRNA recently reported. This article reviews the current findings on the role of LOXL1-AS1 in cancer, and discusses the potential clinical significance and application prospects, in order to provide a theoretical basis and reference for the clinical diagnosis, treatment and screening of prognostic markers for malignant tumors. Methods: The PubMed and Embase databases were searched using the keywords "cancer" or "tumor" or "neoplasm" and "LOXL1-AS1" for publications from 2018 to the present. The English literature was searched, with a focus on relevant articles. These articles validated the role and mechanism of LOXL1-AS1 in different cancers. Key Content and Findings: LOXL1-AS1 is a recently reported novel lncRNA, which is abnormally expressed and upregulated in more than ten cancers, and is positively correlated with adverse clinical features and poor prognosis in cancer patients. LOXL1-AS1 competently binds to a variety of microRNAs to regulate the expression of downstream target genes and regulate related signaling pathways, including proliferation, migration, invasion and inhibition of malignant biological behaviors such as apoptosis. Conclusions: LOXL1-AS1 is expected to become a novel biomarker for cancer diagnosis and treatment, with great potential as an independent prognostic indicator.

[Clinical study on the incidence of femoral head posterior tilt angle in non-displaced femoral neck fractures].

OBJECTIVE: To investigate the occurrence of posterior femoral head tilt after clinical non-displaced femoral neck fracture, and to provide a reference basis for clinical surgery and improvement of disease prognosis. METHODS: Total of 165 patients with non-displaced femoral neck fractures of Garden typeⅠandⅡfrom January 2018 to June 2022 were selected as study subjects including 48 males and 117 females, with an average age of (71.5±8.5) years old ranging from 53 to 89, involving 97 cases of typeⅠand 68 of typeⅡ. On the patient's preoperative sagittal or axial CT film of the hip, the angle formed by the radius line of the femoral head and the midline of the femoral neck was used as the posterior tilt angle of the femoral head (α), and the posterior tilt femoral head angle was measured using the method proposed by Palm. The measured data were divided into 6 groups:α<0°, 0°<α< 5°, 5°≤α<10°, 10°≤α<15°, 15°≤α<20°, α≥20°, and the incidence of different ranges of posterior tilt angle was compared. The sex composition ratio of 165 patients were analyzed and compared, and the age of 65 was used as the cut-off point to compare the incidence of fractures between genders. Patients were divided into the posterior tilt <20° group for 135 cases and the posterior tilt ≥20°group for 30 cases according to the preoperative posterior tilt angle, the differences between two groups in terms of gender and age were analyzed. RESULTS: Among 165 patients with non-displaced femoral neck fractures, 143 cases with poaterior tilt of the femoral head occurred with an incidence of 86.7%. Posterior tilt 0°<α<5° accounted for 36 cases with an incidence of 21.8%;5°≤α<10° accounted for 40 cases with an incidence of 24.2%;10°≤α<15° accounted for 27 cases with an incidence of 16.4%;15°≤α<20° accounted for 10 cases with an incidence of 6.1%;posterior tilt angle α≥20° accounted for 30 cases, the incidence was 18.2%, of which the maximum posterior tilt angle was 42.7°. Statistical analysis showed that the percentage of fractures in the 165 patients selected for this study was significantly higher in female than in male, and that the female group was more likely to have fractures before the age of 65 years compared to the male group. However, gender, age and fracture subtypes (GardenⅠ, Ⅱ) were not influential factors for femoral neck fractures with a preoperative posterior femoral head tilt angle >20°(P>0.05). CONCLUSION: The incidence of femoral head posterior tile in non-displaced femoral neck fractures is relatively high, in which severe posterior tile occurs, and the femoral head posterior tile angle≥20° can reach 18.2%. In patients with closed reduction internal fixation, the fracture end needs to be repositioned as much as possible to reduce the risk of postoperative avascular necrosis of the femoral head. In order to prevent femoral neck fractures, special attention should be paid to anti-osteoporosis treatment for female. Preoperative assessment of posterior tilt is critical for patients of different ages, genders and fracture subtypes (GardenⅠ, Ⅱ).

Expression of lncRNA LINC00943 in lung squamous cell carcinoma and its relationship with tumor progression.

BACKGROUND: Molecular biology has been applied to the diagnosis, prognosis and treatment of various diseases, and long noncoding RNA LINC00943 (lncRNA LINC00943; LINC00943) plays an important role in a variety of cancers. Therefore, this study explored the prognostic role of LINC00943 in lung squamous cell carcinoma (LUSC) and understood its impact on the development of LUSC. METHODS: There are 89 LUSC patients were involved in current assay. By detecting the expression of LINC00943 and miR-196b-5p in tissues and cells, LINC00943 and its correlation with the characteristics of clinical data were analyzed. The biological function of LINC00943 was studied by Transwell migration and invasion assays. In addition, Pearson correlation coefficient and luciferase activity experiments were chosen to characterize the relationship between LINC00943 and miR-196b-5p and explore the mechanism of LINC00943. RESULTS: Compared with normal controls, LINC00943 expression in LUSC tissues and cells was significantly reduced, miR-196b-5p was markedly increased, there was a negative correlation between LINC00943 and miR-196b-5p. According to the in vitro cell experiments, migration and invasion of LUSC cells were suppressed by overexpression of LINC00943. Besides, LINC00943 was demonstrated to have prognostic power and targeting miR-196b-5p was involved in the progression of LUSC. CONCLUSIONS: Overexpression of LINC00943 was molecular sponge for miR-196b-5p that controlled the deterioration of LUSC, which had great potential as a prognostic biomarker for LUSC.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer.

BACKGROUND: A growing number of clinical examples suggest that coronavirus disease 2019 (COVID-19) appears to have an impact on the treatment of patients with liver cancer compared to the normal population, and the prevalence of COVID-19 is significantly higher in patients with liver cancer. However, this mechanism of action has not been clarified. AIM: To investigate the disease relevance of COVID-19 in liver cancer. METHODS: Gene sets for COVID-19 (GSE180226) and liver cancer (GSE87630) were obtained from the Gene Expression Omnibus database. After identifying the common differentially expressed genes (DEGs) of COVID-19 and liver cancer, functional enrichment analysis, protein-protein interaction network construction and screening and analysis of hub genes were performed. Subsequently, the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed. RESULTS: Of 518 common DEGs were obtained by screening for functional analysis. Fifteen hub genes including aurora kinase B, cyclin B2, cell division cycle 20, cell division cycle associated 8, nucleolar and spindle associated protein 1, etc., were further identified from DEGs using the "cytoHubba" plugin. Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation, cell cycle and other functions, and they may serve as potential molecular markers for COVID-19 and liver cancer. Finally, we selected 10 of the hub genes for in vitro expression validation in liver cancer cells. CONCLUSION: Our study reveals a common pathogenesis of liver cancer and COVID-19. These common pathways and key genes may provide new ideas for further mechanistic studies.

Time to sputum culture conversion and its associated factors among drug-resistant tuberculosis patients: a systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors. METHODS: PubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software. RESULTS: A total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1+) (aHR = 0.87,95%CI:0.77,0.99), (grade 2+) (aHR = 0.81,95%CI:0.69,0.95), (grade 3+) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB. CONCLUSION: Patients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m2, lung cavity, sputum smear grading at baseline (Positive, grade 1+, grade 2+, grade 3+) may be risk factors for longer sputum culture conversion time. This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.

Analysis of the potential biological value of pyruvate dehydrogenase E1 subunit ß in human cancer.

BACKGROUND: The pyruvate dehydrogenase E1 subunit ß (PDHB) gene which regulates energy metabolism is located in mitochondria. However, few studies have elucidated the role and mechanism of PDHB in different cancers. AIM: To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer. In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer. METHODS: Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas (TCGA) database. Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases. Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients. The correlation between PDHB and receiver operating characteristic diagnostic curve, clinicopathological staging, somatic mutation, tumor mutation burden (TMB), microsatellite instability (MSI), DNA methylation, and drug susceptibility in pan-cancer was also analyzed. Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment, as well as the co-expression analysis of PDHB and immune checkpoint (ICP) genes. The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing, and the functional enrichment analysis of PDHB-related genes was performed. The study also validated the level of mRNA or protein expression of PDHB in several cancers. Finally, in vitro experiments verified the regulatory effect of PDHB on the proliferation, migration, and invasion of liver cancer. RESULTS: PDHB was significantly and differently expressed in most cancers. PDHB was significantly associated with prognosis in patients with a wide range of cancers, including kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, breast invasive carcinoma, and brain lower grade glioma. In some cancers, PDHB expression was clearly associated with gene mutations, clinicopathological stages, and expression of TMB, MSI, and ICP genes. The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment. In addition, single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells. This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation, migration, and invasion functions of hepatoma cells. CONCLUSION: As a member of pan-cancer, PDHB may be a novel cancer marker with potential value in diagnosing cancer, predicting prognosis, and in targeted therapy.

The Functions and Mechanisms of Long Non-coding RNA SNHGs in Gastric Cancer.

Gastric cancer is one of the most common malignancies worldwide. Despite significant advancements in surgical and adjuvant treatments, patient prognosis remains unsatisfactory. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that lack protein-coding capacity but can participate in various mechanisms of tumor malignancy. Among them, small nucleolar host genes (SNHGs) represent a subgroup of lncRNAs. Studies have revealed their involvement not only in gastric cancer cell proliferation, invasion, migration, epithelialmesenchymal transition (EMT), and apoptosis but also in chemotherapy resistance and tumor stemness. This review comprehensively summarizes the biological functions, molecular mechanisms, and clinical significance of SNHGs in gastric cancer. It provides novel insights into potential biomarkers and therapeutic targets for the exploration of gastric cancer.

[Research progress of caput femoris posterior tilt and its impact on prognosis in nondisplaced femoral neck fractures].

There are still many unresolved problems in the treatment and prognosis of nondisplaced femoral neck fractures, such as nonunion and avascular necrosis of the caput femoris .In order to reduce the risk of various complications after non-displaced femoral neck fractures, the caput femoris posterior tilt of femoral neck fractures and its impact on prognosis have attracted more and more attention. A large number of scholars' studies have found that when the posterior tilt exceeds 20°, the risk of internal fixation failure increases significantly. Based on this concept, we can choose to use primary artificial joint replacement instead of three-screw internal fixation according to the different posterior tilt angles of patients to reduce the incidence of postoperative complications. At the same time, our analysis found that comminution of the posterior segment of the femoral neck would lead to an increase in the posterior inclination angles. The purpose of this review was to investigate the relationship between caput femoris posterior tilt of femoral neck fractures and surgical outcome, and to introduce a new method for measuring caput femoris posterior tilt of the femoral neck.

Rapid adaptation to CDK2 inhibition exposes intrinsic cell-cycle plasticity.

CDK2 is a core cell-cycle kinase that phosphorylates many substrates to drive progression through the cell cycle. CDK2 is hyperactivated in multiple cancers and is therefore an attractive therapeutic target. Here, we use several CDK2 inhibitors in clinical development to interrogate CDK2 substrate phosphorylation, cell-cycle progression, and drug adaptation in preclinical models. Whereas CDK1 is known to compensate for loss of CDK2 in Cdk2-/- mice, this is not true of acute inhibition of CDK2. Upon CDK2 inhibition, cells exhibit a rapid loss of substrate phosphorylation that rebounds within several hours. CDK4/6 activity backstops inhibition of CDK2 and sustains the proliferative program by maintaining Rb1 hyperphosphorylation, active E2F transcription, and cyclin A2 expression, enabling re-activation of CDK2 in the presence of drug. Our results augment our understanding of CDK plasticity and indicate that co-inhibition of CDK2 and CDK4/6 may be required to suppress adaptation to CDK2 inhibitors currently under clinical assessment.

Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

Comprehensive analysis of the role of ICOS ( CD278 ) in pan-cancer prognosis and immunotherapy.

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.

The crosstalking of lactate-Histone lactylation and tumor.

Lactate was once considered to be a by-product of energy metabolism, but its unique biological value was only gradually explored with the advent of the Warburg effect. As an end product of glycolysis, lactate can act as a substrate for energy metabolism, a signal transduction molecule, a regulator of the tumor microenvironment and immune cells, and a regulator of the deubiquitination of specific enzymes, and is involved in various biological aspects of tumor regulation, including energy shuttling, growth and invasion, angiogenesis and immune escape. Furthermore, we describe a novel lactate-dependent epigenetic modification, namely histone lactylation modification, and review the progress of its study in tumors, mainly involving the reprogramming of tumor phenotypes, regulation of related gene expression, mediation of the glycolytic process in tumor stem cells (CSCs) and influence on the tumor immune microenvironment. The study of epigenetic regulation of tumor genes by histone modification is still in its infancy, and we expect that by summarizing the effects of lactate and histone modification on tumor and related gene regulation, we will clarify the scientific significance of future histone modification studies and the problems to be solved, and open up new fields for targeted tumor therapy.

Selenium substituted axitinib reduces axitinib side effects and maintains its anti-renal tumor activity.

Axitinib is a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, which has a strong inhibitory effect on the three isoforms of VEGFR 1-3. Having strong therapeutic efficacy, its broad use is limited by its side effects such as hypertension, proteinuria, cardiovascular damage, and liver and kidney dysfunction. Selenium compounds are broadly reported to have a good protective effect on cardiovascular disease, inflammation, infection, and immune function. In this study, a selenium substitute of axitinib was synthesized, and its anti-renal cell carcinoma activity and side effects were investigated. The results of the study indicated that Se-axitinib had potent antitumor activity on renal cell carcinoma (RCC), alleviated vascular hyperpermeability, and also alleviated axitinib-related side effects including hypertension, liver dysfunction and kidney dysfunction significantly. Therefore, we suggest that Se-axitinib could be a solution to the severe side effects of VEGFR inhibitors and provide evidence to improve the outcome of RCC treatment.