Non-invasive prenatal testing (NIPT) based on fetal free DNA is a non-invasive technique to screen for common fetal aneuploidies by analyzing cell-free fetal DNA (cffDNA) in the peripheral blood of pregnant women. This technique has opened a new era of prenatal screening for its high safety and reliability. In recent years, it has been shown that NIPT can not only screen for fetal aneuploidies, but may also reveal maternal genomic abnormalities. The incidental detection of maternal tumors has aroused widespread concern in the clinical settings. The aim of this review is to systematically summarize the research progress of NIPT technique in incidental detection of maternal tumors, and to discuss its clinical significance, technical challenges, and future development direction. It has been found that multiple chromosome aneuploidies (MCAs) in NIPT detection is one of the important biomarkers suggesting occult maternal malignant tumors. In this paper, the relevant progress of NIPT technique in the incidental discovery of maternal tumors were reviewed in order to provide a reference for individualized and standardized application of NIPT technique in maternal health monitoring.
Humans ; Female ; Pregnancy ; Cell-Free Nucleic Acids/blood* ; Prenatal Diagnosis/methods* ; Incidental Findings ; Neoplasms/genetics* ; Noninvasive Prenatal Testing/methods* ; Aneuploidy ; Fetus/metabolism*

Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

Objective To explore the effects of miR-373 and Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signaling pathways on the M2 polarization of tumor associated macrophages (TAM) in rectal cancer. Methods THP-1 cells were induced into M0/M1/M2 macrophages, M0 macrophages were cocultured with Caco-2 cells to obtain TAM, Flow cytometry was used to detect the expression of CD86 and CD206, Real-time quantitative qPCR and Western blot were used to detect miR-373, inducible nitric oxide synthase (iNOS), toll-like receptor 4 (TLR-4), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), arginase 1 (Arg1), chitinase 3-like 1 (Ym1), resistin like α (Fizz1), IL-10 mRNA and protein levels. TAM were transfected and divided into overexpressing miR-373 group (miR-373-TAM) and control group (miR-NC-TAM), overexpressing miR-373+JAK2-TAM group (miR-373 combined with JAK2-TAM) and control group (miR-373 combined with NC-TAM), and then cocultured with Caco-2 cells. Flow cytometry was used to detect the expression of CD206 in TAM; Real-time quantitative PCR and Western blot were used to detect miR-373, Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels in TAM; CCK-8 assay, colony formation assay, and Transwell assay were used to detect the proliferation, migration, and invasion ability of Caco-2 cells. Thirty nude mice were randomly divided into Caco-2 cells group, Caco-2 cells combined with miR-NC-TAM group, and Caco-2 cells combined with miR-373-TAM group, with 10 mice in each group. Rats in each group were subcutaneously injected with pure Caco-2 cells, Caco-2 cells combined with TAM, and Caco-2 cells combined with TAM overexpressing miR-373. After 4 weeks of cell inoculation, immunofluorescence staining was used to detect F4/80⁺CD206⁺cells level in tumor tissue; Real-time quantitative PCR and Western blot were used to detect miR-373, JAK2, STAT6, Arg1, Ym1, Fizz1, IL-10 mRNA and protein levels in tumor tissues. Results TAM tended to M2 polarization. After overexpression of miR-373, miR-373 level in TAM was increased, while Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels were decreased, proliferation, migration, invasion ability of Caco-2 cells were decreased; Overexpression of JAK2 could partially reverse the effect of overexpression of miR-373 on the M2 polarization of TAM and proliferation, migration, invasion ability of Caco-2 cells. TAM could promote tumor growth; Overexpression of miR-373 could inhibit tumor growth and inhibit M2 polarization of TAM. Conclusion miR-373 could inhibit M2 polarization of TAM in rectal cancer, and miR-373 might inhibit proliferation and metastasis of rectal cancer cells by regulating the JAK2/STAT6 pathway.
MicroRNAs/metabolism* ; Humans ; STAT6 Transcription Factor/genetics* ; Signal Transduction/genetics* ; Animals ; Janus Kinase 2/genetics* ; Mice ; Tumor-Associated Macrophages/metabolism* ; Rectal Neoplasms/pathology* ; Caco-2 Cells ; Mice, Nude ; THP-1 Cells ; Mice, Inbred BALB C ; Cell Polarity ; Male

Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans ; RNA, Long Noncoding/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Esophageal Squamous Cell Carcinoma ; Exosomes/genetics* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Glycolysis/genetics* ; Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Cadherins/genetics*

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Objective To investigate the effect of resveratrol on the tumor microenvironment in osteosarcoma. Methods A C57BL/6 xenograft mouse model was established and treated with resveratrol. Single-cell sequencing was performed to analyze changes in the tumor microenvironment. Immunohistochemistry was used to assess immune cell infiltration, while Western blotting was conducted to examine alterations in cellular signaling pathways. Results Resveratrol significantly inhibited the proliferation of LM8 osteosarcoma cells in C57BL/6 mice compared to the control group. Additionally, CD8⁺ T cell recruitment was enhanced. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was notably downregulated in LM8 osteosarcoma cells following resveratrol treatment. Conclusion Resveratrol promotes CD8⁺ T cell infiltration by inhibiting the JAK2/STAT3 signaling pathway, suggesting its potential as a therapeutic agent in osteosarcoma treatment.
Osteosarcoma/genetics* ; STAT3 Transcription Factor/genetics* ; Resveratrol/pharmacology* ; Animals ; Janus Kinase 2/genetics* ; Signal Transduction/drug effects* ; Tumor Microenvironment/immunology* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice ; Humans ; Cell Proliferation/drug effects* ; Bone Neoplasms/metabolism* ; CD8-Positive T-Lymphocytes/drug effects* ; Xenograft Model Antitumor Assays

Objective To investigate whether PLCB1 expression leads to gastric adenocarcinoma metastasis and poor prognosis, and to preliminarily analyze its mechanism. Methods 122 gastric adenocarcinoma patients and their adjacent non-cancerous tissues were selected, and tissue microarray technology was used to detect the expression levels of PLCB1, epithelial cadherin(E-cadherin), vimentin and CD8⁺ T cells by immunohistochemistry, and scored by two pathologists. According to the immunohistochemical score of PLCB1, the patients were divided into PLCB1 high expression group (IHC>90) and PLCB1 low expression group (IHC≤90). The clinical pathological characteristics, epithelial mesenchymal transition(EMT)-related proteins and CD8⁺ T cells expression differences between the two groups were compared. The overall survival of the patients was collected, and COX regression analysis and Kaplan-Meier curve were used to evaluate the relationship between PLCB1 expression level and prognosis. Results PLCB1 was highly expressed in 55 cases of gastric adenocarcinoma tissues, while only 12 cases in adjacent non-cancerous tissues. The tumor invasion depth, lymph node metastasis degree and TNM stage of the PLCB1 high expression group were higher than those of the PLCB1 low expression group. Chi-square test showed that PLCB1 expression level was negatively correlated with E-cadherin (r=-0.339), positively correlated with vimentin (r=0.211), and negatively correlated with CD8⁺ T cells (r=-0.343). Kaplan-Meier curve analysis showed that the overall survival and disease-free survival of gastric adenocarcinoma patients with high PLCB1 expression were significantly reduced. Multivariate COX regression analysis showed that except for lymph node metastasis, tumor invasion depth, TNM stage, E-cadherin and vimentin were also independent prognostic factors for gastric adenocarcinoma patients. Conclusion PLCB1 is highly expressed in gastric adenocarcinoma, and is closely related to tumor aggressiveness and prognosis. PLCB1 may induce EMT and inhibit CD8⁺ T cell infiltration to affect gastric adenocarcinoma metastasis and immune response.
Humans ; Stomach Neoplasms/genetics* ; Epithelial-Mesenchymal Transition ; Male ; Female ; Middle Aged ; Prognosis ; Adenocarcinoma/genetics* ; Cadherins/metabolism* ; Aged ; Adult ; CD8-Positive T-Lymphocytes/immunology* ; Vimentin/metabolism* ; Lymphatic Metastasis ; Neoplasm Metastasis

Objective To explore the mechanism of TPT1-AS1 targeting miR-324/TWIST1 axis to regulate the proliferation, invasion, migration and angiogenesis of epithelial ovarian cancer (EOC) cells, thereby affecting ovarian cancer (OC) progression. Methods RT-qPCR was used to detect the expression of TPT1-AS1 and miR-324 in 29 OC lesions and adjacent tissue samples. The two OC cell models of TPT1-AS1 overexpression and miRNA324 knockdown were constructed, and the cell proliferation, invasion and migration abilities were detected by CCK-8, Transwell^TM and scratch test. Western blot analysis was used to detect the protein expression levels of TWIST1, epithelial cadherin (E-cadherin), Vimentin, and vascular endothelial growth factor A (VEGF-A) in OC cells. Fluorescence in situ hybridization (FISH) and RNA pull-down experiments were used to verify the interaction between TPT1-AS1 and miR-324. Immunohistochemistry and Targetscan bioinformatics analysis were used to verify the negative regulatory role of miR-324 in the epithelial-mesenchymal transition (EMT) process. Results The TPT1-AS1 expression was significantly higher in OC tissues than that in para-cancerous tissues, while the miR-324 expression was significantly lower. In SKOV3 cells with TPT1-AS1 overexpression, the miR-324 expression decreased significantly, and TPT1-AS1 was negatively correlated with miR-324. It was also found that TPT1-AS1 and miR-324 were co-expressed in OC cells, and there was a direct binding relationship between them. Down-regulation of miR-324 significantly promoted the proliferation, invasion and migration of SKOV3 cells. Further studies revealed that miR-324 had a binding site at the 3'-UTR end of the TWIST1, a key transcription factor for EMT. Inhibiting miR-324 expression increased the transcription level of TWIST1, leading to a decrease in E-cadherin protein expression and an increase in Vimentin protein expression. Additionally, the downregulation of miR-324 resulted in an increased expression level of VEGF-A protein, which in turn enhanced angiogenesis of OC. Conclusion TPT1-AS1 promotes EOC cell proliferation, invasion, migration and angiogenesis by negatively regulating the miR-324/TWIST1 axis, thus promoting the development of OC. These findings provide new potential targets for the diagnosis and treatment of OC.
Humans ; MicroRNAs/metabolism* ; Female ; Cell Movement/genetics* ; Ovarian Neoplasms/blood supply* ; Twist-Related Protein 1/metabolism* ; Cell Line, Tumor ; Neovascularization, Pathologic/genetics* ; Neoplasm Invasiveness ; Carcinoma, Ovarian Epithelial/metabolism* ; Nuclear Proteins/metabolism* ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; RNA, Long Noncoding/metabolism* ; Cadherins/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Vimentin/genetics* ; Angiogenesis

Mannose-binding lectin-associated serine protease 2(MASP-2) is a member of serine protease family and plays a crucial role in activating the complement lectin pathway. When mannose residues on the surface of a pathogen are recognized by mannose-binding lectins (MBL) or fibrinogen collagen (FCN), MASP-2 is activated. This activation then triggers the cleavage of C4 and C2 to form C3 convertase, thereby initiating the lectin pathway of the complement system. Numerous studies have demonstrated that MASP-2 gene polymorphisms and serum levels are closely related with various diseases, including tumors, infectious diseases, autoimmune diseases and so on. In this review, we summarize the relationships between MASP-2 and tumors, infectious diseases, autoimmune diseases. We aim to provide a theoretical basis for the early diagnosis, prognosis evaluation and clinical treatment of various diseases.
Humans ; Mannose-Binding Protein-Associated Serine Proteases/metabolism* ; Neoplasms/metabolism* ; Autoimmune Diseases/genetics* ; Animals ; Polymorphism, Genetic ; Communicable Diseases/genetics*