Hereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by spherical erythrocytes, splenomegaly, and increased osmotic fragility, with ANK1 mutations being the most frequent cause. We identified a novel ANK1 mutation (c.5096G>A, p.R1699K) in a patient with classic HS phenotypes and a family history of hemolytic anemia. To explore its pathogenicity, we performed a series of hematological and morphological analyses. Compared with wild-type mice, the Ank1 c.5198G>A knock-in mice displayed typical HS features. Hematologically, they showed reduced MCV, MCH, and MCHC. The EMA fluorescence intensity was significantly decreased, and RBCs exhibited increased osmotic fragility. Morphologically, peripheral smears revealed abundant spherocytes, and electron microscopy showed a transformation from normal biconcave discs to spherical erythrocytes. Additionally, the Ank1 c.5198G>A knock-in mice presented with significant splenomegaly. Mechanistically, coimmunoprecipitation analysis indicated a significantly weakened association between ankyrin-1 and β-spectrin in the Ank1 c.5198G>A knock-in mice. This study provides in vivo evidence that the Ank1 R1733K mutation impairs erythrocyte membrane stability and cytoskeletal integrity, recapitulating the HS phenotype in mice. Our findings support the pathogenicity of the ANK1 c.5096G>A mutation and offer a useful model for further investigating the molecular mechanisms of HS.

SCHEMBL4796824, a BPR0L075 derivative with antitumor properties, targets tubulin's colchicine binding site and induces DNA damage response in ovarian cancer. Cell counting kit-8 (CCK-8) assay confirmed its anti-proliferative effects, while wound healing and transwell assays demonstrated inhibition of migration and invasion. Flow cytometry showed G2 phase arrest. Molecular docking and immunofluorescence revealed microtubule depolymerization via tubulin binding, analogy with BPR0L075. Real-time qPCR and western blot analysis indicated activation of ATM/Chk2 and ATR/Chk1 pathways by SCHEMBL4796824. Senescence-associated-β-galactosidase (SA-β-gal) staining showed senescence induction. Molecular docking studies suggested potential interaction with CTNNB1. Crucially, functional assays demonstrated inhibition of the Wnt/β-catenin pathway, as evidenced by downregulation of β-catenin and c-MYC. The β-catenin agonist reversed SCHEMBL4796824-induced DNA damage and senescence, establishing a causal link to the observed phenotypes. Notably, these effects were more pronounced in c-MYC amplified SK-OV-3 cells. In summary, SCHEMBL4796824 disrupts the canonical Wnt/β-catenin signaling, inducing DNA damage, and inhibits the Wnt/β-catenin/c-MYC axis, triggering cellular senescence in a pathway-dependent manner, hinting at a novel therapeutic approach.

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer with limited therapeutic options. Motor neuron and pancreas homeobox 1 (MNX1) has been implicated in tumor progression, yet its roles in TNBC immune evasion remain unexplored. In the present study, we analyzed TCGA datasets and performed immunohistochemistry to evaluate MNX1 expression in TNBC tissues. DNA Affinity Purification and sequencing (DAP-seq) were used to identify MNX1 binding motifs. The regulatory relationship between MNX1 and CD24 was validated through dual luciferase reporter assays and expression manipulation in TNBC cell lines. Macrophage-mediated phagocytosis was assessed using in vitro co-culture systems and a humanized macrophage immune reconstruction mouse xenograft model. We found MNX1 expression was significantly elevated in TNBC tissues and correlated with poor patient prognosis. MNX1-knockdown significantly inhibited MDA-MB-468 cell proliferation in vitro and xenograft growth in vivo. In MDA-MB-231 cell, MNX1-overexpression promoted cell proliferation in vitro. We identified "TAATTA" as the MNX1 binding motif and demonstrated that MNX1 directly activates CD24 transcription. MNX1 knockdown in MDA-MB-468 cells enhanced macrophage phagocytosis, while its overexpression in MDA-MB-231 cells reduced phagocytosis. In the humanized mouse model, MNX1 downregulation increased macrophage infiltration and suppressed tumor growth. In summary, our findings reveal that MNX1 promotes TNBC immune evasion through transcriptional regulation of CD24. SIGNIFICANCE: We showed that CD24 is a novel target of transcription factor MNX1. MNX1-driven CD24-overexpression enables TNBC cells to evade from phagocytosis in both co-culturing TNBC cells with macrophage and in humanized macrophage immune reconstruction mouse xenograft model.

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs’ regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.

Heparanase (HPSE), an endo-beta-D-glucuronidase, cleaves heparan sulfate and serves an important role in the tumor microenvironment and thus in tumorigenesis. HPSE is known to promote tumor cell evasion of apoptosis. However, the underlying mechanism of this requires further study. In the present study, the results demonstrated that myeloid cell leukemia-1 (MCL-1), an antiapoptotic protein, and HPSE were upregulated in prostate cancer tissues compared with adjacent normal tissues. In addition, the HPSE inhibitor, OGT 2115, inhibited PC-3 and DU-145 prostate cancer cell viability in a dose-dependent manner, with IC50 values of 20.2 and 97.2 mu M, respectively. Furthermore, annexin V/PI double-staining assays demonstrated that OGT 2115 induced apoptosis in prostate cancer cells. OGT 2115 treatment markedly decreased MCL-1 protein expression levels, whereas RNA interference-mediated downregulation of MCL-1 and OGT 2115 drug treatment synergistically induced apoptosis in PC-3 and DU-145 cells. In vivo, OGT 2115 40 mg/kg (ig) significantly inhibited PC-3 cell xenograft growth in nude mice and increased the positive TUNEL staining rate of xenograft tissues. It was therefore hypothesized that MCL-1 was an important signaling molecule in OGT 2115-induced apoptosis. The results of the present study also demonstrated that the proteasome inhibitor, MG-132, markedly inhibited the downregulation of MCL-1 protein expression levels induced by OGT 2115. However, the protein synthesis inhibitor, cycloheximide, did not affect the role of OGT 2115 in regulating MCL-1. In summary, the results of the present study demonstrated that the proapoptotic activity of OGT 2115 was achieved by downregulating MCL-1.

Gut microbiota affects the gut–brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers—TNF-α, IL-1β, IL-6, and iNOS—in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.

Supplementary Table 1. Differentially Expressed Probesets comparing samples from ovarian cancer patients with chemotherapy treatment to samples without chemotherapy treatment

mTOR inhibition decreases MMP9 expression. A, Everolimus treatment for 24 hours did not reduced MMP2 protein levels in SUM225 cells. B, C and D figures were the MMP-9 IHC quantification data measuring average optical density using ImageJ d 1.47 software. B, one-week Everolimus treatments at 2 mg/kg/day significantly decreased MMP9 protein levels in the mammary gland of MMTV/neu mice (n=3). C, one-week-Everolimus treatments at 2 mg/kg decreased MMP9 protein levels in the mammary gland of SUM225-MIND mouse mammary tissues detected by IHC (n=4). D, one-week-rapamycin treatments at 2 mg/day reduced MMP9 protein levels in mammary glands of DCIS patients detected by IHC. **p<0.01 and * p<0.05 represents the comparison between control vehicle and everolimus treatment groups or pre-treatment and post-treatment group, respectively, t-test.

Metastasis is an obstacle to the clinical treatment of aggressive breast cancer (BC). Studies have shown that high mobility group A1 (HMGA1) is abnormally expressed in various cancers and mediates tumor proliferation and metastasis. Here, we provided more evidence that HMGA1 mediated epithelial to mesenchymal transition (EMT) through the Wnt/β-catenin pathway in aggressive BC. More importantly, HMGA1 knockdown enhanced antitumor immunity and improved the response to immune checkpoint blockade (ICB) therapy by upregulating programmed cell death ligand 1 (PD-L1) expression. Simultaneously, we revealed a novel mechanism by which HMGA1 and PD-L1 were regulated by the PD-L1/HMGA1/Wnt/β-catenin negative feedback loop in aggressive BC. Taken together, we believe that HMGA1 can serve as a target for the dual role of anti-metastasis and enhancing immunotherapeutic responses.

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The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.

BACKGROUND:Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a transmembrane glycoprotein that is expressed by natural killer (NK) cells and certain subsets of T cells. However, its expression profiles and functions in solid tumor progression remain poorly defined.METHODS:In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT cell viability assay, soft agar colony formation assay and a human renal cell carcinoma (RCC) cell xenograft model in nude mice, we examined whether KIR2DL4 is expressed by RCC and its possible roles in RCC progression.RESULTS:We confirmed that KIR2DL4 is overexpressed by RCC cells. MTT and soft agar cloning assays showed that KIR2DL4 knockdown delayed cell proliferation and viability in RCC cell lines, Caki-1 and 769-P, in vitro. By contrast, KIR2DL4 overexpression promoted Caki-1 cell proliferation both in vitro and in vivo, which was observed in a BALB/c-nu/nu xenograft mouse model. Moreover, RNA sequencing data demonstrated that the differentially expressed genes found between parallel-controlled and Caki-1 cells overexpressing KIR2DL4 were highly associated with cancer development, of which those related to the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were particularly enriched, immunoblotting data showed that the level of AKT phosphorylation was higher or lower in KIR2DL4 overexpressing or KIR2DL4 knocking-down Caki-1 cells compared with that in the parallel-controlled cells. In addition, PI3K inhibitor wortmannin treatment and KIR2DL4-shRNA transfection further deregulated the levels of phosphorylated AKT and Caki-1 cell proliferation.CONCLUSIONS:Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression associated with PI3K/AKT activation.

Background: The prognosis of breast cancer varies according to the molecular subtype. Transmembrane 4 L six family 1 (TM4SF1) exhibits different expression patterns among the molecular subtypes of breast cancer. However, the expression profile of TM4SF1 in hormone receptor HR+HER2- breast cancer remains unclear.Methods: TM4SF1 mRNA levels were examined in major subclasses of breast cancer by analyzing The Cancer Genome Atlas (TCGA) datasets. In addition, TM4SF1 protein and mRNA levels in HR+HER2- breast cancer tissue samples were determined by immunohistochemistry and Western blot assay. The effect of TM4SF1 on cell proliferation was evaluated using MTT, colony formation, 3D organoid, and xenograft models, following the TM4SF1 overexpression or knockdown.Results: TCGA database analysis demonstrated that TM4SF1 was downregulated in breast cancer compared with the healthy adjacent breast tissue. In addition, the expression of TM4SF1 in basal-like one and the mesenchymal TNBC tissue was higher than that of the healthy adjacent breast tissue. Other types, including the luminal androgen receptor–positive TNBC tissue, expressed lower levels of TM4SF1. Immunohistochemistry and real-time quantitative PCR assays demonstrated that the TM4SF1 protein and mRNA levels were downregulated in the HR+HER2- breast cancer tissue compared with the healthy adjacent tissue. Moreover, the TM4SF1 overexpression reduced the viability of MCF-7 and ZR-75-1 breast cancer cells, whilst reducing the number of colonies and 3D-organoids formed by these cell lines. By contrast, TM4SF1 knockdown led to an increased MCF-7 cell proliferation. However, in the TNBC cell line, MDA-MB-231, TM4SF1 silencing reduced cell proliferation. In vivo, the TM4SF1 overexpression inhibited MCF-7 xenograft growth in a nude mouse model, which was associated with the downregulation of the Ki-67 expression, apoptosis induction, and inhibition of the mTOR pathway.Conclusion: TM4SF1 is downregulated in HR + HER2-breast cancer, and the overexpression of TM4SF1 suppresses cell proliferation in this cancer subtype.

Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC), especially in BRAF-like PTC, by analyzing The Cancer Genome Atlas (TCGA) database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5-specific antagonist TC LPA5 4 treatment inhibited CGTH-W3, TPC-1, B-CPAP, and BHT-101 cell proliferation, CGTH-W3 and TPC-1 cell migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH-W3 xenograft growth in nude mice. We also found that LPAR5-specific antagonist TC LPA5 4, PI3K inhibitor wortmannin, or mTOR inhibitor rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH-W3 and TPC-1 cells. Stimulating CGTH-W3 cells transfected with pEGFPC1-Grp1-PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)-triphosphate, which indicates that PI3K was activated by LPA directly. The p110β-siRNA instead of p110α-siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110β. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or the PI3K/Akt signal may be a novel therapeutic strategy for treating thyroid cancer.

Background : Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a transmembrane glycoprotein that is expressed by natural killer (NK) cells and certain subsets of T cells. It has been reported to serve an important role in the immune response. However, its expression profiles and function in solid tumor progression remain poorly defined. Methods : In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT assay, soft agar colony formation assay and a renal cell carcinoma (RCC) cell xenograft model in nude mice, we examined whether KIR2DL4 is expressed by RCC and its possible roles in RCC progression. Results : We confirmed that KIR2DL4 is overexpressed by RCC cells. MTT and soft agar cloning assays showed that KIR2DL4 knockdown delayed cell proliferation in RCC cell lines, Caki-1 and 769-P, in vitro . By contrast, KIR2DL4 overexpression promoted Caki-1 cell proliferation both in vitro and in vivo, which was observed in a BALB/c-nu/nu xenograft mouse model. Moreover, RNA sequencing data demonstrated that the differentially expressed genes between vector controlled and KIR2DL4-overexpressed Caki-1 cells were highly associated with cancer development, of which those related to the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway were particularly enriched. Immunoblotting data showed that the level of AKT phosphorylation was higher in KIR2DL4-overexpressing Caki-1 cells compared with that in the parallel-controlled cells. Conclusions : Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression through the PI3K/AKT signaling pathway.

Malignant gliomas are a heterogeneous group of brain tumors with a poor prognosis, which is largely due to its aggressive invasiveness and angiogenesis. In recent years, it has been found that multiple long noncoding RNAs (lncRNAs) participate in a wide range of biological functions including angiogenesis through the regulation of gene expression in cancers. In this study, we investigate and report the novel role of lncRNA SLC26A4‐AS1 in gliomas, with a novel mechanism involving transcription factors NFKB1 and NPTX1. We determined that SLC26A4‐AS1 was downregulated in human glioma tissues and cells. Furthermore, overexpression of SLC26A4‐AS1 or NPTX1 restrained the aggressiveness of glioma cells and their pro‐angiogenic ability. SLC26A4‐AS1 was also found to upregulate NPTX1 by recruiting NFKB1 into the NPTX1 promoter. Moreover, silencing of either NPTX1 or NFKB1 restored the aggressive and pro‐angiogenic properties of glioma cells in the presence of SLC26A4‐AS1. Taken together, we demonstrate that SLC26A4‐AS1 promotes NPTX1 transcriptional activity by recruiting NFKB1 and thus exerting antiangiogenic effects on glioma cells. This study provides an experimental basis for the intervention of SLC26A4‐AS1 in the treatment of gliomas.

Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker that is highly expressed in various types of human cancer, and a protein kinase target for cancer therapy that is attracting increasing interest. However, no drug candidates targeting DCLK1 kinase have been developed in clinical trials to date. XMD-17-51 was found herein to possess DCLK1 kinase inhibitory activities by cell-free enzymatic assay. In non-small cell lung carcinoma (NSCLC) cells, XMD-17-51 inhibited DCLK1 and cell proliferation, while DCLK1 overexpression impaired the anti-proliferative activity of XMD-17-51 in A549 cell lines. Consequently, XMD-17-51 decreased Snail-1 and zinc-finger-enhancer binding protein 1 protein levels, but increased those of E-cadherin, indicating that XMD-17-51 reduces epithelial-mesenchymal transition (EMT). Furthermore, sphere formation efficiency was significantly decreased upon XMD-17-51 treatment, and XMD-17-51 reduced the expression of stemness markers such as β-catenin, and pluripotency factors such as SOX2, NANOG and OCT4. However, the percentage of ALDH+ cells was increased significantly following treatment with XMD-17-51 in A549 cells, possibly due to EMT inhibition. In combination, the present data indicated that XMD-17-51 inhibited DCLK1 kinase activity in a cell-free assay with an IC50 of 14.64 nM, and decreased DCLK1 protein levels, cell proliferation, EMT and stemness in NSCLC cell lines. XMD-17-51 has the potential to be a candidate drug for lung cancer therapy.

OBJECTIVE:The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate the potential ability of SGLT2 inhibitors to attenuate cancer growth of SGLT2-expressing cancer cells, but there is little known about the effects of SGLT2 inhibitors on breast cancer. The goal in this research was to assess the anticancer activity of SGLT2 inhibitors in breast cancerin vitro and in vivo.METHODS:We test the SGLT2 expression in breast cancer using immunohistochemistry and immunoblot assay. MTT cytotoxicity assay, colony formation assay and human breast cancer cells nude mice xenograft model were performed to detect the effects of SGLT2 inhibitors on cancer cell proliferation and growth. Flow Cytometry assay was performed to determine if the SGLT2 inhibitors induced cell cycle arrest and apoptosis.RESULTS:We proved that SGLT2 expresses in breast cancer cell lines and human breast tumor tissue samples. SGLT2 inhibitors Dapagliflozin and Canagliflozin exhibited a potent anti-proliferative effect in breast cancer cells as demonstrated by MTT, clonogenic survival assay in vitro and xenograft growth model in vivo. Furthermore, we found that SGLT2 inhibitors arrested cell cycle in G1/G0 phase and induced cell apoptosis. Western blot analysis demonstrated that treatment with SGLT2 inhibitors increased the phosphorylation of Amp-activated protein kinase (AMPK) and decreased the phosphorylation of 70 kDa ribosomal protein S6 kinase 1 (p70S6K1) in breast cancer cells.CONCLUSIONS:These findings indicate that SGLT2 inhibitor-therapy induced AMPK-mediated cell cycle arrest and apoptosis, which is a potential novel strategy for the treatment of breast cancer.

目的 在整个基因组范围内整合分析染色体变异与基因差异表达来探讨肾透明细胞癌的发病机制.方法 从肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载肾透明细胞癌DNA拷贝数和mRNA表达数据,使用GISTIC进行拷贝数变异分析;使用R软件包edgeR进行基因差异表达分析;并对差异表达基因进行KEGG和GO通路富集分析.结果 GISTIC发现381个拷贝数扩增,1287个缺失;R语言包发现1171个基因mRNA表达上调,567个基因mRNA表达下调;相关性检测发现13个拷贝数增加的基因表达上调,17个拷贝数降低的基因表达下调.GO和KEGG分析发现这些差异基因主要富集在多个致癌基因,且参与肿瘤的发生、发展及免疫逃逸的信号转导.结论 整合分析相关拷贝数变异和基因表达差异,能为肾透明细胞癌的诊断和治疗提供分子标记和靶点.

目的:应用生物信息学方法筛选脑胶质瘤的预后风险长链非编码RNA(lncRNA).方法:从开放的癌症基因图谱(TCGA)和基因型组织表达(GTEx)数据平台下载脑胶质瘤样本转录水平数据,采用R语言比较分析脑胶质瘤和正常脑胶质样本差异表达基因,使用Cox分析构建风险模型,通过DAVID基因功能和KEGG通路数据库对差异表达基因进行功能注释和通路富集分析.利用qPCR评价HOXA-AS2的表达量与脑胶质瘤的临床组织特征之间的关系.结果:通过比较分析脑胶质瘤样本和正常脑组织样本基因组表达数据,获得差异表达的lncRNA 424个(211个上调,213个下调),mRNA 3827个(1618个上调,2209个下调).构建了包含9个lncRNA的风险模型,参与介导的信号转导通路主要集中于免疫缺陷病毒感染,神经信号转导等相关通路.qPCR方法验证HOXA-AS2在脑胶质瘤中高表达.结论:筛选出HOXA-AS2可能是脑胶质瘤的预后风险lncRNA,为后续脑胶质瘤的机制研究提供参考依据.