Establishment of glioma prognosis nomogram based on the function of meox1 in promoting the progression of cancer.

Background: Gliomas stand out as highly predominant malignant nervous tumors and are linked to adverse treatment outcomes and short survival periods. Current treatment options are limited, emphasizing the need to identify effective therapeutic targets. The heterogeneity of tumors necessitates a personalized treatment approach with an effective grouping system. Meox1 has been implicated in promoting tumor progression in diverse cancers; nonetheless, its role in gliomas remains unelucidated. Material/methods: Utilized immunohistochemistry to assess the expression of Meox1 protein in glioma tissues. Proliferation and invasion assays were conducted on wild-type and meox1-overexpressed glioma cells using the CCK8 and Transwell assays, respectively. The expression levels of meox1 and its related genes in gliomas were obtained from Chinese Glioma Genome Atlas (CGGA), along with the corresponding patient survival periods. LASSO regression modeling was employed to construct a scoring system for patients with gliomas, categorizing them into high-/low-risk groups. Additionally, a nomogram for predicting the survival period of patients with glioma was developed using multivariate logistic analysis. Results: We attempted, for the first time, to demonstrate heightened expression of Meox1 in glioma tumor tissues, correlating with significantly increased invasion and proliferation abilities of glioma cells following meox1 overexpression. The scoring system effectively stratified patients with glioma into high-/low-risk groups, revealing differences in the survival period and immunotherapy efficacy between the two groups. The integration of this scoring system with other clinical indicators yielded a nomogram capable of effectively predicting the survival period of individuals with gliomas. Conclusions: Our study established a stratified investigation system based on the levels of meox1 and its related genes, providing a novel, cost-effective model for facilitating the prognosis prediction of individuals with glioma.

Cancer-Associated Fibroblasts Affect Tumor Metabolism and Immune Microenvironment in Gastric Cancer and Identification of Its Characteristic Genes.

Background: Cancer-associated fibroblasts (CAFs) have reported widely involved in cancer progression. However, its underlying mechanism in gastric cancer is still not clarified. Methods: The data used in this study were all downloaded from the Cancer Genome Atlas database. R software and the R packages were used for all the analyses. Results: In our study, we first quantified the CAFs infiltration using the ssGSEA algorithm. The clinical correlation result showed that CAFs were associated with a worse prognosis and clinical features. Pathway enrichment also indicated several oncogenic pathways in GC patients with high CAFs infiltration, including epithelial-mesenchymal transition (EMT), myogenesis, allograft rejection, the inflammatory response, and IL2/STAT5 signaling. Furthermore, FNDC1 and RSPO3 were identified as the characteristic genes of CAFs through two machine learning algorithms, LASSO logistic regression and SVM-RFE. The following analysis showed that FNDC1 and RSPO3 were associated with more progressive clinical features and had a good prediction efficiency of the CAFs infiltration status in GC patients. Pathway enrichment and genomic instability were performed to explore the underlying mechanisms of FNDC1 and RSPO3. Immune infiltration analysis showed that CAFs were positively correlated with M2 macrophages. Moreover, we found that the GC patients with low CAFs infiltration were more sensitive to immunotherapy. Also, the CAFs, FNDC1, and RSPO3 could generate a certain effect on the sensitivity of doxorubicin, mitomycin, and paclitaxel. Conclusions: In summary, our study comprehensively investigated the role of CAFs in GC, which might be associated with immunotherapy sensitivity. Meanwhile, FNDC1 and RSPO3 were identified as the underlying targets of GC.

Latent Class Analysis of Subphenotypes in Intermediate-Stage Hepatocellular Carcinoma after Transarterial Chemoembolization.

Background: Transarterial chemoembolization (TACE) is the standard first-line therapy for intermediate-stage hepatocellular carcinoma (HCC). However, no latent-classing indices, concerning repeat conventional TACE or switching to another treatment, have been incorporated into the guidelines. Methods: The unsupervised latent class modeling was applied to identify subphenotypes using the clinical and medical imaging data of 1517 HCC patients after the first TACE from four hospitals (derivation cohort: 597 cases; validation cohort: 920 cases); modeling was conducted independently in each cohort. We then explored the relationship of subphenotypes with clinical outcomes in both cohorts and response to treatment strategies after the first TACE in the derivation cohort. Results: Independent latent class models suggested that a three-class model was optimal for both cohorts. In both cohorts, we identified a TACE-refractory subphenotype (Phenotype 1: PS score 1, stage progress, more intrahepatic lesions, and new intrahepatic lesions), TACE-responsive subphenotype (Phenotype 3: PS score 0, No intrahepatic lesions and new intrahepatic lesions), compared to TACE-intermediate subphenotype (Phenotype 2). Compared to Phenotype 1 or 2, patients in Phenotype 3 had significantly lower 3-month or 3-year mortality (all P<0.001). In the derivation cohort, the effects of treatment strategy (surgery/ablation vs. repeat TACE vs. stop TACE) differed significantly in phenotype 2 but not in phenotype 3 (P=0.721 for interaction). Conclusions: Latent class models identified three subphenotypes for HCC after the first TACE treatment. Differences were significant in clinical outcome and response to treatment strategy after the first TACE among three subphenotypes.

A multicenter-retrospective study of non-small-cell lung carcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations: different subtypes of EGFR exon 19 deletion-insertions exhibit the clinical characteristics and prognosis of non-small cell lung carcinoma.

Background: The aim of this study was to investigate the clinical features, immunohistochemistry (IHC), compound mutation, and prognosis of patients with non-small cell lung cancer (NSCLC) harboring exon 19 deletion-insertion mutations. Methods: This retrospective analysis included 4,666 NSCLC patients harboring epidermal growth factor receptor (EGFR) mutations in a multi-center study from January 2017 to December 2020, and 69 patients with EGFR exon 19 deletion-insertions were taken to account. Next-generation sequencing (NGS) was used to detect the subtype of EGFR exon 19 deletion-insertions. These mutations were correlated with clinical features, immunophenotype and molecular characteristics of tumors and outcomes of patients. Results: Sixty-nine patients with EGFR exon 19 deletion-insertions were analyzed in this study, comprising 24 cases (34.8%) with L747_P753delinsS, 9 cases (13.1%) with L747_A750delinsP, both 5 cases (7.2%) in E746_A750delinsQP, E746_S752delinsV and both 4 cases (5.8%) in E746_T751delinsA and L747_T751delinsP. Twenty-nine males (42%) and 40 females (58%), with a median age of 59.7 years; 12 (21.7%) participants were smokers and 54 (78.3%) were nonsmokers. The compound mutations were tumor protein 53 (TP53) (45.83%), phosphoinositide-3-kinase (PIK3CA) (11.59%), and almost 16.67% in retinoblastoma 1 (RB1), melanocyte stimulating hormone (MSH), and myelocytomatosis (MYC). The best overall response was complete response (CR) in 47.8% of patients, partial response (PR) in 33.3% and stable disease (SD) in 13.1% of patients. Correlation between immunoreactivity of Napsin A, thyroid transcription factor (TTF), cytokeratin (CK7), surfactant proteins B (SPB), and the subtypes of EGFR exon 19 deletion-insertion was significantly statistically different (P<0.05). The disease control rate (DCR) was 29%. The median progression-free survival (mPFS) and 95% confidence interval (CI) of exon 19 deletion-insertion subtypes were 14.821 (9.917 to 19.726) months for L747_P753delinsS, 23.500 (15.877 to 31.123) months for L747_A750delinsP, 26.667 (11.731 to 41.603) months for L747_T751delinsP, and 11.713 (7.786 to 15.639) months for the others. Patients receiving treatment with 3rd generation tyrosine kinase inhibitors (TKI) had the shortest progression-free survival (PFS) (median: 7.179, 95% CI: 3.969-10.388). Conclusions: The subtypes of exon 19 deletion-insertion exhibited different clinical characteristics compared with other common mutations. Our finding argued in favor of analyzing the correlation between immunoreactivity and the subtypes of EGFR exon 19 deletion-insertion. The EGFR exon 19 deletion-insertion mutations exhibited limited sensitivity to 3rd generation TKI. Moreover, in light of therapeutic effect for the subtype, L747_T751delinsP achieved longer PFS.

Management of a uterine serosal heterotopic pregnancy after in vitro fertilization in a woman with bilateral salpingectomy: A case report and literature review.

RATIONALE: Heterotopic pregnancy (HP) is defined as the simultaneous presence of intrauterine pregnancy and ectopic pregnancy (EP). HP after bilateral salpingectomy is extremely rare and may lead to serious complications if it is misdiagnosed and untreated timely. Here, we presented the first reported case of uterine serosal HP in a woman after assisted reproductive technology with bilateral salpingectomy because of bilateral tubal ectopic pregnancy. PATIENT CONCERNS: A 27-years-old pregnant woman after in vitro fertilization with bilateral salpingectomy complained of a sudden onset of unprovoked abdominal pain, which was persistent and dull. She denied vaginal bleeding. DIAGNOSES: Serum beta-human chorionic gonadotropin levels are difficult to predict HP. Transvaginal ultrasonography demonstrated 1 gestational sac in the uterine cavity and 1 thick-walled cystic mass over the upper of the uterus, with a large amount of fluid in the Pouch of Douglas. Emergency laparotomy revealed a uterine serosal pregnancy combined with intrauterine pregnancy. INTERVENTIONS: This patient was successfully managed via emergency laparotomy to remove residual tissue and repair the rupture of the uterine serosal pregnancy. OUTCOMES: At postoperative 4 days, repeat transvaginal ultrosonography presented 1 intrauterine gestational sac with a visible fetal bud and cardiac tube pulsation. Now the patient recover well and is in an ongoing pregnancy. LESSONS: It is noteworthy that HP/ectopic pregnancy is still not prevented after bilateral salpingectomy. In cases of multiple embryo transfer, even if intrauterine pregnancy has been established, it is important to rule out HP/ectopic pregnancy in time. Early diagnosis and early management can significantly improve clinical outcomes.

An ultrasensitive electrochemical immunosensor for the detection of CD146 based on TiO2 colloidal sphere laden Au/Pd nanoparticles.

An ultrasensitive electrochemical immunosensor for the detection of cluster of differentiation 146 antigen (CD146) based on TiO2 colloidal sphere laden Au/Pd nanoparticles (Au/Pd@TiO2) was developed. In this work, reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) was applied as an electrode modifying material to modify the surface of a glassy carbon electrode (GCE). Au/Pd@TiO2 was used as the secondary-antibody (Ab2) label for the fabrication of the immunosensor. Amperometric response of the immunosensor for electrocatalytic reduction of hydrogen peroxide (H2O2) was recorded. Electrochemical impedance spectroscopy (EIS) proved that fabrication of the immunosensor was successful. The anti-CD146 primary antibody (Ab1) was immobilized on the rGO-TEPA modified GCE by a cross-linking reagent of glutaraldehyde (GA). With Ab1 immobilized onto the rGO-TEPA modified GCE and Ab2 linked with Au/Pd@TiO2, the immunosensor displayed a wide linear range (0.0050-20 ng mL(-1)), a low detection limit (1.6 pg mL(-1)), good reproducibility, good selectivity and acceptable stability. The designed sensing strategy may provide a potential application in the detection of other tumor markers.

Sandwich-type electrochemical immunosensor using dumbbell-like nanoparticles for the determination of gastric cancer biomarker CA72-4.

A novel and sensitive nonenzymatic sandwich-type electrochemical immunosensor for the detection of gastric cancer biomarker CA72-4 was fabricated using dumbbell-like PtPd-Fe3O4 nanoparticles (NPs) as a novel kind of label. The signal amplification strategy, using the synergetic effect present in PtPd-Fe3O4 to increase the reduction ability of the NPs toward H2O2, improved the sensitivity of the immunosensor. The immunosensor was constructed by modifying glassy carbon electrode with reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) for effective immobilization of primary anti-CA72-4 antibody (Ab1). Secondary anti-CA72-4 antibody (Ab2) was adsorbed onto the PtPd-Fe3O4 NPs. The proposed immunosensor displayed a wide linear range (0.001-10 U/mL) with the low detection limit (0.0003 U/mL). The immunosensor was evaluated for serum samples, receiving satisfactory results. Therefore, the immunosensor possesses excellent clinical value in cancer screening as well as convenient point-of-care diagnostics.

An electrochemical immunosensor for ultrasensitive detection of carbohydrate antigen 199 based on Au@Cu(x)OS yolk-shell nanostructures with porous shells as labels.

A novel and sensitive electrochemical immunosensor for ultrasensitive detection of pancreatic cancer biomarker carbohydrate antigen 199 (CA199) was proposed by using Au@Cu(x)OS yolk-shell nanostructures with porous shells as labels for signal amplification. Au@Cu(x)OS yolk-shell nanostructures exhibit high electrocatalytic activity toward the reduction of hydrogen peroxide (H2O2) as analytical signal. Moreover, secondary antibody (Ab2) can adsorb on the surface of Au@Cu(x)OS with porous shells which has large surface area and could greatly increase the probability of Ab2-antigen interactions thereby leading to higher sensitivity. Reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), containing abundant amine groups, was supported Au nanoparticles as a support platform to immobilize the primary antibody (Ab1). The resulting sensing interface of rGO-TEPA/AuNPs could provide a large electroconductive surface area, allowing high loadings of the biological recognition elements as well as the occurrence of electrocatalytic and electron-transfer processes. Under optimal conditions, the immunosensor exhibited a wide linear response to CA199 ranging from 0.001 to 12 U/mL with a low detection limit of 0.0005 U/mL. The designed immunosensor displayed good precision, high sensitivity, acceptable stability and reproducibility, and has been applied to the analysis of serum with satisfactory results. The proposed method provides a new promising platform of clinical immunoassay for other biomolecules.

Ultrasensitive enzyme-free immunoassay for squamous cell carcinoma antigen using carbon supported Pd-Au as electrocatalytic labels.

A novel nonenzymatic sandwich-type electrochemical immunosensor has been developed to detect squamous cell carcinoma antigen (SCCA). Nitrogen-doped graphene sheet (N-GS) was used to increase capacity of capturing primary antibodies (Ab1). Carbon-supported Pd-Au binary nanoparticles (Pd-Au/C) were synthesized and used to label secondary antibodies (Ab2). The specific binding of SCCA and antibodies enabled a quantitative attachment of Pd-Au/C on the electrode surface. Electrocatalytic analysis showed that the prepared Pd-Au/C exhibit excellent electrocatalytic activity towards hydrogen peroxide (H2O2). We use current response of electrocatalytic labels Pd-Au/C to detect the concentration of SCCA. The unique nonenzymatic immunosensor exhibits a relatively wide linear range from 0.005 to 2 ng mL(-1) and high sensitivity with a low detection limit of 1.7 pg mL(-1). The immunsensor also shows good reproducibility (4.2%) and stability (5.8%), which makes it an enormous application prospect in clinical research.

A sandwich-type immunosensor using Pd-Pt nanocrystals as labels for sensitive detection of human tissue polypeptide antigen.

A sandwich-type immunosensor was developed for the detection of human tissue polypeptide antigen (hTPA). In this work, a graphene sheet (GS) was synthesized to modify the surface of a glassy carbon electrode (GCE), and Pd-Pt bimetallic nanocrystals were used as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for catalyzing hydrogen peroxide (H2O2) was recorded. And electrochemical impedance spectroscopy was used to characterize the fabrication process of the immunosensor. The anti-human tissue polypeptide antigen primary antibody (Ab1) was immobilized onto the GS modified GCE via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). With Ab1 immobilized onto the GS modified GCE and Ab2 linked on Pd-Pt bimetallic nanocrystals, the immunosensor demonstrated a wide linear range (0.0050-15 ng ml(-1)), a low detection limit (1.2 pg ml(-1)), good reproducibility, good selectivity and acceptable stability. This design strategy may provide many potential applications in the detection of other cancer biomarkers.

Simultaneous electrochemical detection of cervical cancer markers using reduced graphene oxide-tetraethylene pentamine as electrode materials and distinguishable redox probes as labels.

A novel, highly sensitive electrochemical immunoassay was proposed for the simultaneous determination of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCCA) for the diagnosis of cervical cancer. Using an electrochemical analysis technique, two well-separated peaks were generated by neutral red and thionine, making the simultaneous detection of the two analytes on the electrode possible. Reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), containing more amino groups, was of benefit to immobilize the primary antibody (Ab1) through an amidation reaction. Au@mesoporous carbon CMK-3 was synthesized and incubated with two secondary antibodies (Ab2) and different redox probes (neutral red and thionine) to fabricate the electrochemical immunosensor label intending to improve the analytical performance of the immunosensor. The immunosensor was prepared with a sandwich structure based on the peak current change of neutral red and thionine before and after the antigen-antibody reaction. The results showed that the immunosensor had a wide linear range, low detection limit, good reproducibility and stability. The method has been applied to the analysis of serum samples with satisfactory results.

An ultrasensitive enzyme-free electrochemical immunosensor for CA125 using Au@Pd core-shell nanoparticles as labels and platforms for signal amplification.

A facile and sensitive enzyme-free sandwich-type immunosensor for the detection of carbohydrate antigen 125 (CA125) was designed based on Au@Pd core-shell nanoparticles. Au@Pd nanoparticles were used both as electrode-modifying materials to immobilize the primary antibody (Ab1) of CA125 and as labels of secondary antibody (Ab2). The covalent bond between palladium nanoparticles and available amine groups of Ab1 enables the anchoring of larger amounts of Ab1 while the high stability and bioactivity of Ab1 can be reserved. Au@Pd nanoparticles show high electrocatalytic activity toward hydrogen peroxide (H2O2) reduction. The encapsulated Au nanoparticles can also accelerate the electron transfer. A high-performance electrochemical immunosensor was constructed based on the signal amplification of Au@Pd nanoparticles. Under optimal conditions, the immunosensor exhibited a wide linear response to CA125 ranging from 0.002 to 20 U mL-1 with a low detection limit of 0.001 U mL-1. The designed immunosensor displayed an excellent analytical performance with high sensitivity and stability. This strategy was successfully proved to be a simple method, which could be easily extended to other protein analysis.

Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia.

OBJECTIVE: MicroRNA-100 (miR-100), a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML), but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML. METHODS: The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed. RESULTS: Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P < 0.001) was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French-American-British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively). Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients. CONCLUSION: This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML.