GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis

Primary tumors of the central nervous system(CNS)are classified into over 100 different histological types.The most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts for over 57%of these tumors.Glioblastoma(GBM)is the most common and fatal tumor of the CNS,with strong growth and invasion capabilities,which makes complete surgical resection almost impossible.Despite various treatment methods such as surgery,radiotherapy,and chemotherapy,glioma is still an incurable disease,and the median survival time of patients with GBM is shorter than 15 months.Thus,molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis.Glutamate ionotropic receptor kainate type subunit 1(GRIK1)is essential for brain function and is involved in many mental and neurological diseases.However,GRIK1’s pathogenic roles and mechanisms in GBM are still unknown.Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM,consistent with The Cancer Genome Atlas database.Knockdown of GRIK1 retarded GBM cells growth,migration,and invasion.Taken together,these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.

Bioinformatics comprehensive analysis confirmed the potential involvement of SLC22A1 in lower-grade glioma progression and prognosis

Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains unclear.Methods:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various tumors.Silence of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)progression.Results:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p<0.05).Importantly,we found the potential involvement of SLC22A1 in occurrence and progress of certain cancers,with a pronounced impact on LGG.Further examination of the SLC22A1-LGG relationship revealed its status as an independent risk factor for LGG,suggesting its potential involvement in regulating diverse immune pathways and metabolic activities.Chinese Glioma Genome Atlas(CGGA)data supported the reliability of the risk score as a prognostic and recurrence indicator,emphasizing the accuracy of the nomograph(1,3,and 5-year-AUC>0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell growth.Conclusion:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG prognosis.SLC22A1 has only been proved to support cellular function previously.Our findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of gliomas.Additionally,we provide a highly practical prediction model for estimating the survival rate of LGG patients.

Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in HCC.METHODS Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in HCC.Using immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our results.The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint expression.Finally,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining assays.RESULTS Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor prognosis.Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor.In HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation levels.Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup.The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor prognosis.CONCLUSION As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

BMI1 overexpression is correlated with a poor prognosis and immune infiltration in hepatocellular carcinoma

Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.

Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma

BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.

Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system

BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in Liver Hepatocellular Carcinoma: Implications for Prognosis and Therapeutic Targeting - A Secondary Publication

The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses.Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that our model effectively predicted the response of patients to immune-based treatments.Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

The lactylation index predicts the immune microenvironment and prognosis of pan-cancer patients

Background:Protein lactylation is a new way for the“metabolic waste”lactic acid to perform novel functions.Nevertheless,our understanding of the contribution of protein lactylation to both tumor progression and therapeutic interventions remains imited.The construction of a scoring system for lactylation to predict the prognosis of pancancer patients and to evaluate the tumor immune microenvironment(TIME)would improve our understanding of the clinical significance of lactylation.Methods:Consensus clustering analysis of lactylation-related genes was used to cluster 177 pancreatic adenocarcinoma(PAAD)patients.Subsequently,a scoring system was developed using the least absolute shrinkage and selection operator(LASSO)regression.Internal validation and external validation were both conducted to assess and confirm the predictive accuracy of the scoring system.Finally,leucine rich repeat containing 1(LRRC1),a newly discovered lactylation-related gene,was analyzed in PAAD in vitro.Results:Utilizing the profiles of 332 lactylation-related genes,a total of 177 patients with PAAD were segregated into two distinct groups.LacCluster^(high) patients had a poorer prognosis than LacCluster^(low) patients.Through the differential analysis between the LacCluster^(high) and LacCluster^(low) groups,we identified additional genes associated with lactylation.These genes were then integrated to construct the LacCluster-enhanced system,which enabled more accurate prognosis prediction for patients with PAAD.Then,a lactylation index containing three genes(LacI-3)was constructed using LASSO regression.This was done to enhance the usability of the LacCluster-enhanced system in the clinic.Compared to those in the LacI-3^(high) subgroup,patients in the LacI-3^(low) subgroup exhibited increased expression of immune checkpoint-related genes,more immune cell infiltration,lower tumor mutation burdens,and better prognoses,indicating a“hot tumor”phenotype.Moreover,knocking down the expression of LRRC1,the hub gene in the LacI-3 scoring system,inhibited PAAD cell invasion,migration,and proliferation in vitro.Ultimately,the significance of LacI-3 across cancers was confirmed.Conclusion:Our findings strongly imply that protein lactylation may represent a new approach to diagnosing and treating malignant tumors.

血管生成拟态、Cripto-1在非小细胞肺癌组织中的表达及其临床意义

目的筛查预测非小细胞肺癌(NSCLC)侵袭、转移及预后的生物因子。方法采用免疫组织化学方法检测145例NSCLC患者血管生成拟态(vasculogenic mimicry,VM)的形成和Cripto-1的表达水平。结果Cripto-1在NSCLC中的表达率(56.6%)显著高于正常组织(36.6%)(P<0.001)。37.2%的NSCLC组织中存在VM,但在正常肺组织中未发现VM(P<0.05)。Cripto-1表达与VM形成显著相关(P<0.001)。高水平的Cripto-1和VM形成会导致总生存期(overall survival,OS)降低(P<0.001)。多因素分析表明,Cripto-1上调、VM形成、淋巴结转移和TNM分期是反映NSCLC预后的重要指标。结论Cripto-1和VM水平在NSCLC中显著升高,可能作为免疫标志物来预测该肿瘤的侵袭、转移和预后。

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer

BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

Comprehensive analysis of cell-extracellular matrix protein Ras suppressor-1 in function and prognosis of gastrointestinal cancers

BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.

老年急性脑梗死患者血清Del-1和IL-17水平变化及与梗死面积和预后的关系

目的 探究老年急性脑梗死(ACI)患者血清内皮发育调节基因-1(Del-1)、白细胞介素-17(IL-17)水平与脑梗死面积、病情严重程度及预后的关系。方法 回顾性收集2019-01-2021-12厦门大学附属东南医院收治的126例老年ACI患者(病例组)及105名健康体检者(对照组)的临床资料,根据脑梗死面积将病例组患者分为大面积梗死组(梗死最大直径>5 cm,n=14)、中面积梗死组(梗死最大直径3~5 cm,n=53)和小面积梗死组(梗死最大直径<3 cm,n=59);根据NIHSS评分分为重症组(NIHSS评分≥16分,n=13)、中症组(5分<NIHSS评分<15分,n=58)和轻症组(NIHSS评分≤5分,n=55);根据m RS评分分为预后良好组(mRS评分≤2分,n=81)和预后不良组(mRS评分>2分,n=45)。采用荧光免疫法检测血清Del-1、IL-17水平,受试者工作特征(ROC)曲线评估血清Del-1、IL-17水平预测老年ACI患者预后的价值。结果 病例组吸烟史比例、收缩压、舒张压、糖化血红蛋白、血清IL-17水平均高于对照组,血清Del-1水平低于对照组(P<0.05)。不同脑梗死面积患者血清Del-1水平比较,小面积梗死组>中面积梗死组>大面积梗死组;血清IL-17水平比较,小面积梗死组<中面积梗死组<大面积梗死组(P<0.05)。轻症组血清Del-1水平高于中症组、重症组(P<0.05),不同病情严重程度患者血清IL-17水平比较,重症组>中症组>轻症组(P<0.05)。预后良好组患者血清Del-1水平高于预后不良组,血清IL-17水平低于预后不良组(P<0.05)。ROC曲线分析显示,血清Del-1、IL-17预测ACI患者预后的AUC值分别为0.763、0.747(P<0.05)。结论 老年ACI患者血清Del-1水平较低,IL-17水平较高,二者与患者脑梗死面积、病情严重程度和预后关系密切,可作为预测老年ACI患者预后的可靠指标。

NRG1、HER3在前列腺癌组织中的表达及其与临床病理特征和预后的关系

目的研究前列腺癌(PC)组织中神经调节蛋白1(NRG1)、人表皮生长因子受体3(HER3)表达与临床病理特征及预后的关系。方法选取2015年2月—2020年2月吉林省人民医院泌尿外科诊治PC患者96例,免疫组织化学检测组织中NRG1、HER3表达;Kaplan-Meier曲线(Log-Rank检验)比较不同NRG1、HER3表达对PC患者预后的影响;COX回归分析PC患者预后的影响因素。结果PC癌组织中NRG1、HER3阳性率分别为78.13%(75/96)、75.00%(72/96),高于癌旁组织6.25%(6/96)、8.33%(8/96)(χ^(2)/P=101.670/<0.001,87.771/<0.001)。TNM分期Ⅲ期、Gleason评分>7分及术前PSA水平≥20μg/L患者癌组织中NRG1、HER3阳性率大于TNM分期Ⅰ~Ⅱ期、Gleason评分≤7分及术前PSA水平<20μg/L(χ^(2)/P=6.181/0.013,8.533/0.003;7.731/0.005,6.769/0.009;6.508/0.011,7.376/0.007)。NRG1阳性组、HER3阳性组3年累积无进展生存率分别低于NRG1阴性组、HER3阴性组(χ^(2)/P=4.267/0.039,5.499/0.019)。TNM分期Ⅲ期、Gleason评分>7分、术前PSA≥20μg/L、NRG1阳性,HER3阳性是影响PC患者预后的独立危险因素[OR(95%CI)=1.448(1.118~1.875),1.401(1.138~1.724),1.353(1.059~1.728),1.338(1.057~1.692),1.293(1.014~1.649)]。结论PC癌组织中NRG1、HER3表达升高,与PC不良临床病理特征相关,是新的评估PC预后的肿瘤标志物。

不同Child-Pugh分级肝硬化患者血清TSP-1、球蛋白/胆碱酯酶的表达水平差异及其疾病预后危险因素分析

目的分析不同Child-Pugh分级肝硬化患者血清凝血酶敏感蛋白-1(TSP-1)、球蛋白/胆碱酯酶的表达水平差异及其疾病预后危险因素。方法回顾性选取2020年2月至2023年2月新疆医科大学第一附属医院收治的70例肝硬化患者作为主要研究对象,根据Child-Pugh分级将其分为Child-Pugh A级组(n=20),Child-Pugh B级组(n=34),Child-Pugh C级组(n=16),另选取同期在本院进行体检的50名健康人群作为对照组。采用酶联免疫吸附试验法检测4组及肝硬化不同预后患者的血清TSP-1、球蛋白、胆碱酯酶、球蛋白/胆碱酯酶表达水平;采用双变量Spearman相关性检验血清TSP-1、球蛋白、胆碱酯酶、球蛋白/胆碱酯酶与肝硬化患者Child-Pugh分级和预后的相关性;建立多因素Logistic模型分析影响肝硬化患者预后的独立危险因素,并绘制受试者工作特征(ROC)曲线分析血清TSP-1、球蛋白/胆碱酯酶对肝硬化预后的预测价值。结果与对照组比较,Child-Pugh A级组、Child-Pugh B级组、Child-Pugh C级组患者的血清TSP-1、球蛋白、球蛋白/胆碱酯酶表达水平较高,血清胆碱酯酶表达水平较低;与Child-Pugh A级组患者比较,Child-Pugh B级组、Child-Pugh C级组患者的血清TSP-1、球蛋白、球蛋白/胆碱酯酶表达水平较高,血清胆碱酯酶表达水平较低;与Child-Pugh B级组比较,Child-Pugh C级组患者的血清TSP-1、球蛋白、球蛋白/胆碱酯酶表达水平较高,血清胆碱酯酶表达水平较低,差异均有统计学意义(P<0.05)。与预后良好组比较,预后不良组血清TSP-1、球蛋白、球蛋白/胆碱酯酶表达水平较高,血清胆碱酯酶表达水平较低,差异均有统计学意义(P<0.05)。肝硬化患者血清TSP-1、球蛋白/胆碱酯酶与Child-Pugh分级和预后均呈正相关(P<0.05)。多因素Logistic分析结果显示,Child-Pugh分级、TSP-1、球蛋白/胆碱酯酶均是影响肝硬化患者预后的独立危险因素(P<0.05)。血清TSP-1、球蛋白/胆碱酯酶与TSP-1+球蛋白/胆碱酯酶预测肝硬化患者预后的曲线下面积值分别为0.814、0.824、0.885。结论血清TSP-1、球蛋白/胆碱酯酶异常表达与肝硬化Child-Pugh分级及其预后均存在一定关联,可作为肝硬化患者的Child-Pugh分级及预后的辅助预测指标。

慢性肾小球肾炎患者MCP-1和sFlt-1表达与肾功能及预后的相关性研究

目的:分析慢性肾小球肾炎患者血清单核细胞趋化蛋白-1(MCP-1)和可溶性血管内皮细胞生长因子受体1(sFlt-1)水平变化及其与肾功能和预后的关系。方法:纳入2018-01—2020-03本院收治的慢性肾小球肾炎患者122例(研究组),选取同时期本院体检健康者128例(对照组)。研究组依据肾功能损害情况分为A组(肾功能正常16例)、B组(轻中度肾功能损害88例)、C组(重度肾功能损害18例);根据随访结局,将患者分为肾功能衰竭组(22例)和病情缓解组(100例)。采用酶联免疫吸附法(ELISA)检测受试者MCP-1、sFlt-1水平。采用全自动生化分析仪检测所有受试者血尿素氮(BUN)、血肌酐(Scr)水平,采用慢性肾脏疾病流行病学合作研究公式(CKD-EPI)估算肾小球滤过率(eGFR)。Pearson法分析MCP-1、sFlt-1与BUN、Scr、eGFR的相关性。采用受试者工作特征(ROC)曲线评价血清MCP-1、sFlt-1水平预测慢性肾小球肾炎患者预后的价值。结果:与对照组相比,研究组MCP-1、sFlt-1、BUN、Scr水平较高(P<0.05),eGFR较低(P<0.05)。C组BUN、Scr、MCP-1、sFlt-1水平明显高于A组、B组(P<0.05),B组BUN、Scr、MCP-1、sFlt-1水平明显高于A组(P<0.05)。Pearson相关性分析显示,MCP-1与BUN、Scr均呈正相关(P<0.05),与eGFR呈负相关(P<0.05),sFlt-1与BUN、Scr均呈正相关(P<0.05),与eGFR呈负相关(P<0.05)。与病情缓解组相比,肾功能衰竭组患者清中MCP-1、sFlt-1水平较高(P<0.05)。ROC分析显示,血清MCP-1、sFlt-1水平预测慢性肾小球肾炎患者预后的AUC分别为0.967、0.965,MCP-1联合sFlt-1预测慢性肾小球肾炎患者预后的AUC为0.984,灵敏度100.00%,特异度94.00%。结论:慢性肾小球肾炎患者血清MCP-1、sFlt-1水平明显上升,可作为患者预后评估的潜在生物学指标。

OGDHL、FHL1在非小细胞肺癌组织中的表达及其临床意义

目的分析OGDHL、4个半LIM结构域蛋白1(FHL1)在非小细胞肺癌组织中的表达水平及其临床意义。方法选取80例非小细胞肺癌患者癌组织标本、癌旁组织标本(距肿瘤边缘4cm处),采用免疫组织化学染色法检测所有标本组织中OGDHL、FHL1表达水平。采用χ^(2)检验分析OGDHL、FHL1表达与患者病理特征的关系,采用Kaplan-Meier生存曲线分析OGDHL、FHL1表达与患者预后的关系,多因素Cox回归模型分析非小细胞肺癌患者预后的影响因素。结果非小细胞肺癌患者癌组织OGDHL高表达率明显低于癌旁组织(35.00%vs 62.50%,P<0.05),FHL1高表达率明显高于癌旁组织(67.50%vs 40.00%,P<0.05)。OGDHL、FHL1表达水平与非小细胞肺癌患者TNM分期、淋巴结转移、分化程度密切相关(P<0.05)。OGDHL高表达患者术后5年总生存率为82.14%,低表达患者术后5年总生存率为36.54%,两者比较差异有统计学意义(P<0.05);FHL1高表达患者术后5年总生存率为40.74%,低表达患者术后5年总生存率为76.92%,两者比较差异有统计学意义(P<0.05)。单因素分析得出,TNM分期、淋巴结转移、分化程度、OGDHL表达、FHL1表达均与非小细胞肺癌患者预后密切相关(P<0.05)。TNMⅢ期、淋巴结转移、低分化、OGDHL低表达、FHL1高表达均为影响非小细胞肺癌患者预后的独立危险因素(P<0.05)。结论非小细胞肺癌患者癌组织中OGDHL蛋白呈低表达,FHL1蛋白呈高表达,两者表达水平与非小细胞肺癌患者的临床病理特征及预后密切相关,能够作为评估患者预后的有效指标。

M1型肿瘤相关巨噬细胞在肝细胞癌组织中浸润的意义

背景与目的:肿瘤相关巨噬细胞(tumor-associated macrophages,TAM)是肿瘤微环境中的主要基质细胞,在肿瘤进展过程中发挥重要作用,本研究旨在探究肝细胞癌(hepatocellular carcinoma,HCC)中M1型TAM浸润的临床意义。方法:收集2012年1月—2020年12月在南通大学附属南通第三医院接受手术的HCC患者石蜡包埋组织样本320例,采用免疫组织化学法检测CD86标记的M1型TAM在HCC组织中分布情况,计算阳性细胞密度,根据细胞密度分组:大于平均密度(29个/mm^(2))判定为高密度组,小于或等于平均密度为低密度组;统计分析M1型TAM密度与HCC临床病理学特征、肿瘤浸润CD8^(+)T淋巴细胞之间的相关性及预后意义;采用免疫组织化学法检测程序性死亡配体-1(programmed death ligand-1,PD-L1)的表达情况,根据CD86、PD-L1细胞密度将病例分4组:CD86^(+)高密度组中PD-L1高密度(CD86^(high)PD-L1^(high))和PD-L1低密度(CD86^(high)PD-L1^(low))组;CD86^(+)低密度组中PD-L1高密度(CD86^(low)PD-L1^(high))和PD-L1低密度(CD86^(low)PDL1^(low))组,分析CD86^(+)M1型TAM密度联合PD-L1表达的预后意义。本研究通过南通大学附属南通第三医院伦理委员会批准(伦理编号:EK2022005)。结果:CD86^(+)M1型TAM主要分布于肿瘤间质中;其高密度率为44.7%(143/320)。CD86^(+)M1型TAM密度与CD8^(+)肿瘤浸润细胞毒性T淋巴细胞密度呈正相关(P<0.001)、与乙型肝炎病毒表面抗原(hepatitis B virus surface antigen,HBsAg)阳性呈负相关(P=0.003),与患者性别、年龄、肝硬化、肿瘤大小、组织学分级、微血管侵犯等临床病理学指标均无明显相关性;CD86^(+)M1型TAM高密度组患者总生存期(overall survival,OS)、无病生存期(disease-free survival,DFS)优于低密度组,差异均有统计学意义(P均<0.001)。多因素Cox比例风险回归模型分析显示,低密度CD86^(+)M1型TAM是评估OS和DFS的独立风险因子(OS:HR=1.468,P=0.022;DFS:HR=2.233,P<0.001)。CD86^(high)PD-L1^(high)组HCC患者OS、DFS差于CD86^(high)PD-L1^(low)组,两者差异有统计学意义(P均<0.05)。CD86^(low)PD-L1^(high)组OS、DFS差于CD86^(low)PD-L1^(low)组,两者OS差异有统计学意义(P<0.05),DFS差异无统计学意义。结论:HCC组织中存在高密度CD86^(+)M1型TAM提示患者预后良好,并且是独立的预后因子。HCC组织表达PD-L1提示肿瘤侵袭性增强,患者预后差。

NLRP1、NLRP3、Caspase-1在子宫内膜异位症中的表达及对预后复发的影响

目的探究NLRP1、NLRP3、Caspase-1在不同严重程度子宫内膜异位症(EMS)中的表达及其对预后的影响。方法选择2017年2月至2020年2月在临沂市人民医院行腹腔镜手术治疗的244例EMS患者为研究组;按临床分期,将患者分为Ⅰ~Ⅱ期162例,Ⅲ~Ⅳ期82例;另选同期因良性卵巢囊肿行腹腔镜手术的77例患者为对照组,对比不同严重程度EMS患者异位内膜组织中NLRP1、NLRP3和Caspase-1的表达情况。将244例EMS患者分为复发组37例与未复发组207例,通过单因素分析,初步筛选EMS患者预后复发的影响因素,且采用多因素Logistic回归分析,进一步筛选独立危险因素。应用Logistic回归模型结合限制性立方样条模型(RCS),分析EMS患者异位内膜组织中NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量与预后复发的剂量-反应关系。依据独立危险因素构建并验证列线图预测模型。结果EMS患者严重程度分期NLRP1、NLRP3及Caspase-1表达的分布比较,差异均有统计学意义(χ^(2)值分别为9.827、4.916、4.258,P<0.05);生殖道感染NLRP1、NLRP3及Caspase-1表达的分布比较,差异均有统计学意义(χ^(2)值分别为6.746、13.166、11.643,P<0.05)。研究组不同严重程度异位内膜组织中NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量与对照组比较,差异均有统计学意义(F值分别为18.546、22.582、19.361,P<0.05)。NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量均在研究组Ⅳ期达到最高值,分别为4.30±0.62、5.59±0.77和2.66±0.68。复发组与未复发组的EMS严重程度分期、生殖道感染、术前痛经史的分布比较,差异均有统计学意义(χ^(2)值分别为22.544、18.153、8.882,P<0.05);复发组与未复发组的C反应蛋白(CRP)、白细胞计数(WBC),以及异位内膜组织中NLRP1 mRNA、NLRP3 mRNA和Caspase-1 mRNA表达量比较,差异均有统计学意义(t值分别为3.727、5.486、13.935、28.167、23.003,P<0.05)。多因素Logistic回归分析显示,EMS严重程度分期(OR=1.476,95%CI:1.149~1.826)、生殖道感染(OR=1.256,95%CI:1.028~1.403),以及NLRP1 mRNA(OR=3.076,95%CI:1.363~4.371)、NLRP3 mRNA(OR=1.965,95%CI:1.685~2.354)、Caspase-1 mRNA(OR=2.245,95%CI:1.232~3.152)表达量均是EMS患者预后复发的独立危险因素(P<0.05)。RCS模型分析显示,在NLRP1 mRNA表达量为2.525(OR=3.076,95%CI:1.363~4.371)、NLRP3 mRNA表达量为3.402(OR=1.965,95%CI:1.685~2.354)、Caspase-1 mRNA表达量为1.877(OR=2.245,95%CI:1.232~3.152)处,发生预后复发的风险最大。利用危险因素建立列线图模型,模型具有良好的区分度、准确性。结论随着NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量的升高,子宫内膜异位症预后复发的危险性随之升高。严重程度分级、生殖道感染,以及NLRP1 mRNA、NLRP3 mRNA、Caspase-1 mRNA表达量均是子宫内膜异位症患者预后复发的独立危险因素。