CD97、CD55和C1q联合检测在结核性胸腔积液和恶性胸腔积液鉴别诊断中的应用价值

目的探究CD97、CD55和C1q联合检测在结核性胸腔积液(TPE)和恶性胸腔积液(MPE)鉴别诊断中的应用价值。方法选取2023年赣南医学院第一附属医院收治的150例胸腔积液(PE)患者为研究对象,依据病理诊断分为TPE组(78例)和MPE组(72例),比较2组一般临床资料及CD97、CD55和C1q水平。分析CD97、CD55、C1q及其联合检测在TPE与MPE鉴别诊断中的应用价值。结果2组患者年龄、性别、吸烟史、糖尿病史、胸膜结节、胸膜厚度、发热、胸痛等对比差异均无统计学意义(P>0.05)。MPE组CD97、C1q水平低于TPE组,而CD55水平高于TPE组(均P<0.05)。ROC曲线分析显示,CD97在鉴别诊断TPE和MPE时的AUC为0.718,以113.53 ng·mL^(-1)为临界值,其敏感度、特异度为69.44%、70.51%;CD55在鉴别诊断TPE和MPE时的AUC为0.735,以69.43 ng·mL^(-1)为临界值,其敏感度、特异度为81.94%、55.13%;C1q在鉴别诊断TPE和MPE时的AUC为0.690,以8.91 mg·L^(-1)为临界值,其敏感度、特异度为98.61%、38.46%;CD97、CD55和C1q联合在鉴别诊断TPE和MPE时的AUC为0.753,敏感度、特异度为58.33%、92.31%。结论CD97、CD55、C1q检测对TPE和MPE均有一定鉴别诊断价值,但三者联合诊断价值更大,特异度更高。

CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing.However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

小干扰RNA抑制CD97的表达及其对胃癌细胞迁移和侵袭能力的影响

目的:设计合成有效的siRNA-CD97,体外转染胃癌细胞株,观察CD97表达改变及其与胃癌细胞株迁移、侵袭能力改变的关系。方法:采用AGS和MGC803胃癌细胞株。针对CD97基因设计siRNA,采用化学法合成,筛选出最有效的siRNA-CD97。siRNA-CD97转染胃癌细胞后分别用real-time RT-PCR、免疫荧光流式细胞术检测CD97 mRNA和蛋白表达的改变,MTT法检测细胞活性的改变,并用Transwell细胞迁移和侵袭实验检测细胞迁移和侵袭能力的变化。结果:在siRNA-CD97转染后48 h,real-time RT-PCR结果显示AGS和MGC803细胞CD97 mRNA的表达量相对于未转染的细胞分别下降了(89.34±9.95)%和(95.42±1.93)%。转染后72 h,流式细胞术结果显示AGS细胞CD97EGF和CD97stalk抗原的表达强度相对于未转染的细胞分别下降了(19.29±3.45)%和(30.11±5.93)%,MGC803细胞CD97EGF和CD97stalk抗原的表达强度相对于未转染的细胞分别下降了(26.25±5.73)%和(16.22±3.23)%。MTT法检测结果显示,siRNA-CD97转染前后细胞的吸光度值没有显著差异。迁移和侵袭实验结果显示,AGS细胞siRNA-CD97转染组迁移和侵袭细胞相对于未转染组分别下降了(67.63±12.03)%和(68.02±15.63)%,MGC803细胞转染组迁移和侵袭细胞相对于未转染组分别下降了(14.92±2.03)%和(22.09±5.43)%。结论:胃癌细胞转染siRNA-CD97能够抑制CD97 mRNA和蛋白表达,随着CD97表达的降低,细胞迁移和转移的能力也明显减弱。

直肠癌浸润前沿CD97与其配体CD55的表达及预后影响

目的 探讨直肠癌浸润前沿区域CD97和配体CD55的表达与肿瘤复发转移及预后的关系.方法 用免疫组化方法检测71例直肠癌组织及30例正常结直肠组织CD97和CD55的表达情况.结果 直肠癌组织CD97、CD55表达水平显著高于正常肠黏膜组织,浸润前沿区域癌细胞CD97高表达患者肿瘤复发和/或转移率（67.8%）显著高于低表达患者（30.0%）,浸润前沿区域间质CD55高表达患者复发和/或转移率（64.5%）显著高于低表达患者（32.5%）（均P〈0.05）.浸润前沿区域癌细胞CD97表达与间质CD55表达呈正相关（r=0.392,P〈0.05）.单因素分析显示淋巴结转移、TNM Ⅱ～Ⅳ期、浸润前沿癌细胞CD97高表达为影响术后生存率的危险因素（均P〈0.05）.多因素分析显示淋巴结转移及浸润前沿癌细胞CD97高表达是影响直肠癌预后的独立危险因素（均P〈0.05）.结论 直肠癌浸润前沿区域CD97及其配体CD55表达水平与肿瘤复发转移以及预后密切相关.

胃癌组织中CD97^(STALK)和CD55的表达及其临床病理学意义

目的检测CD97STALK和其细胞配体CD55在胃癌组织及其相应的正常胃黏膜组织中的表达分布,分析这一对受体-配体分子与胃癌患者临床病理学特征之间的关系,探讨CD97STALK和CD55在胃癌发生、发展中的作用机制。方法选取39例经外科手术切除及组织病理学证实的胃癌患者的癌组织标本及相应的正常胃黏膜组织,应用RT-PCR技术和冰冻切片免疫组化染色方法,分别在mRNA和蛋白水平进行检测,并将两个分子的表达水平与患者临床病理学参数进行比较。结果大部分胃癌组织都有CD97STALK的阳性染色。CD97STALK强阳性染色位于胃肿块边沿散在分布的单个瘤细胞和小簇的肿瘤细胞。在临床Ⅰ期和Ⅱ、Ⅲ、Ⅳ期两组胃癌患者的癌组织中CD97STALK阳性表达差异有显著性(P<0.05);在肿瘤浸润深度为T1与T2、T3、T4两组胃癌患者的癌组织之间差异也有显著性(P<0.05)。肿瘤浸润深度为T1的胃癌患者中几乎均有CD55的阳性表达,在肿瘤浸润深度为T1与T2、T3、T4两组胃癌患者的癌组织之间,CD55的阳性表达差异有显著性(P<0.05)。CD97STALK和CD55在早期胃癌中呈现优势表达。胃印戒细胞癌胞浆频繁出现CD97STALK和CD55强阳性染色。胃癌组织CD55与CD97STALK表达高度相关(r=0.73)。结论CD97STALK通过与其细胞配体CD55直接的受体-配体作用,在胃癌发生、发展中发挥作用,CD97STALK和CD55有可能成为早期胃癌诊断、治疗和预后的分子标志。

CD97-CD55蛋白复合体在乳腺恶性肿瘤组织中的表达及临床意义

目的探讨CD97-CD55蛋白复合体在乳腺恶性肿瘤组织中的表达与临床病理因素的关系和评判预后的价值。方法收集212例乳腺恶性肿瘤及358例乳腺良性肿瘤组织石蜡标本制备组织芯片,采用免疫组化SP法检测CD97抗原表位CD97^(EGF)、CD97^(Stalk)和CD55的表达,结合临床资料分析其与临床病理因素联系。设计CD97和CD55寡核苷酸探针,应用显色原位杂交技术检测CD97mRNA和CD55mRNA在乳腺良、恶性肿瘤组织中的表达。采用Cox比例风险模型分析影响乳腺恶性肿瘤预后风险因素,Kaplan-Meier曲线法进行生存分析。结果 CD97^(EGF)和CD97^(Stalk)在乳腺恶性肿瘤组织中表达率分别为53.3%(113/212)和65.1%(138/212)。CD55在乳腺良、恶性肿瘤组织中均有表达。显色原位杂交显示CD97mRNA和CD55mRNA在乳腺良、恶性肿瘤组织中染色强度差异均有统计学意义(均P<0.01)。Cox比例风险模型分析显示肿瘤大小、阳性淋巴结转移数目、TNM分期、CD97^(EGF)阳性表达是影响乳腺恶性肿瘤预后的独立危险因子。结论乳腺恶性肿瘤组织可检测到CD97-CD55蛋白复合体表达,CD97^(Stalk)和CD97^(EGF)两个不同抗原表位可能在CD97参与肿瘤发生、发展机制中存在着一定的差异。乳腺恶性肿瘤组织CD97^(EGF)阳性表达可作为预后判断指标之一。

胃黏膜相关淋巴组织淋巴瘤中环氧化酶－2和CD97的表达与预后的关系

目的探讨环氧化酶2（COX-2）和CD97在胃黏膜相关淋巴组织（MALT）淋巴瘤中的表达及与预后的关系。方法采用Envision二步法对47例胃MALT淋巴瘤进行COX-2和CD97免疫组化染色，并对其幽门螺杆菌（Hp）感染、肿瘤临床分期、浸润深度、肿瘤大小、复发率、化疗和放疗情况等指标作单因素和多因素COX回归分析。结果（1）肿瘤的COX-2及CD97阳性表达率分别为48．9％及87．2％，它们的表达与肿瘤临床病理分期、浸润深度、肿瘤大小明显相关（均P〈005），COX-2的表达还与Hp感染有关（P〈0．01）；（2）生存分析显示，COX-2阳性患者的平均生存时间（59．9个月）短于阴性患者（77．8个月），但两组间的差异无统计学意义（P〉O05）；CD97强阳性患者平均生存时间392个月，显著短于非强阳性患者的100．3个月（P〈0．01）。肿瘤临床病理分期是胃MALT淋巴瘤预后的独立危险因素（风险度为3．041，回归系数为1．112，形以d统计量为13．985，P〈0．01），且与预后呈负相关；而COX-2和CD97均不是影响预后的独立危险因素。结论COX-2和CD97的表达水平与肿瘤进展密切相关，Hp感染可上调COX-2的表达。

CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway

AIM: To investigate the mechanism underlying the promoting role of CD97 in gastric cancer cell proliferation and invasion. METHODS: Two types of exosomes released by gastric cancer cells with high(SGC/wt) or low(SGC/kd) CD97 expression were isolated by ultracentrifugation and identified by electron microscopy and western blot analysis. The influences of the two exosomes on gastric cancer cell proliferation and invasion were investigated by proliferation and Matrigel invasion assays. Exosomal mi RNAs were subsequently isolated from the two samples and their mi RNA profiles were compared via microarray assay analysis. Reverse transcriptionquantitative real-time polymerase chain reaction was used to validate the microarray assay. Target genes of the differently expressed micro RNAs were predicted based on five independent algorithms and were then subjected to gene oncology enrichment and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis. After identifying the pathway that was the most likely altered, tumor cells were treated with the two exosomes at different concentrations, and the pathway activation was identified through western blot analysis.RESULTS: Exosomes isolated from SGC/wt cells significantly promoted tumor cell proliferation in a dose-dependent manner in vitro. SGC/wt exosomesalso significantly elevated the invasiveness of both SGC/wt(129.67 ± 8.327 vs 76.00 ± 5.292, P < 0.001) and SGC/kd(114.52 ± 9.814 vs 45.73 ± 4.835, P < 0.001) cells as compared to the exosomes released by SGC/kd cells. Microarray assay of the two exosomes revealed that 62 mi RNAs were differently regulated with a signal intensity of > 500 and a false discovery rate < 0.05. The following KEGG analysis defined the MAPK signaling pathway as the most likely candidate pathway that regulated tumor cell proliferation and invasion. Through western blot analysis, significant up-regulations of phosphorylated MAPKs, including extracellular signal-regulated kinase, Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase, were detected in a dose-dependent manner in the SGC/wt exosomes treated groups, confirming activation of the MAPK signaling pathway stimulated by SGC/wt exosomes.CONCLUSION: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosomemediated MAPK signaling pathway, and exosomal mi RNAs are probably involved in activation of the CD97-associated pathway.

Role of CD97^(stalk) and CD55 as molecular markers for prognosis and therapy of gastric carcinoma patients

Objectives： To explore the mechanism of development and aggressiveness in gastric carcinomas by investigating the expression and role of CD97 and its cellular ligand CD55 in gastric carcinomas. Methods： Tumor and corresponding normal mucosal tissue, collected from 39 gastric carcinoma patients, were examined by immunohistochemistry and RT-PCR for the expression of CD97 and CD55. Results： CD97^stalk was strongly stained on scattered tumor cells or small tumor cell clusters at the invasion front of gastric carcinomas. The expression of CD97^stalk was frequently observed in tumors of stage Ⅰ and T1 gastric carcinoma patients. The expression of CD97^stalk between Stage Ⅰ and Stage Ⅱ, Ⅲ, Ⅳ specimens showed significant difference （P〈0.05）, between T1 and T2, T3, T4 specimens also showed significant difference （P〈0.05）. Specimens with tumor invasion depth limited in mucosa of T1 specimens showed higher positive CD55 expression than specimens with the same tumor invasion depth in T2, T3, T4 specimens, the expression of CD55 between T1 and T2, T3, T4 specimens was significantly different （P〈0.05）. There was strong correlation between the distribution patterns of CD97^stalk and CD55 on tumor tissues （r=0.73, P〈0.05）. Signet ring cell carcinomas frequently contained strong CD97^stalk and CD55-staining. Conclusions： Our results suggest that CD97^stalk is probably involved in the growth, invasion and aggressiveness of gastric carcinomas by binding its cellular ligand CD55. CD97^stalk and CD55 could be useful as molecular markers for prognosis and therapy of gastric carcinoma patients.

The clinical significance of CD97, NF-kB and COX-2 ingastric MALT lymphomas

Background and Objectives: Increased expression of the CD97, nuclear factor-kB (NF-kB) and cyclooxygenase-2 (COX-2) has been found to play an important role in development of many cancers, including gastric neoplasm. However, the expression and biological behavior of CD97, NF-kB and COX-2 in gastric MALT (mucosa-associated lymphoid tissue) lymphoma has not been well investigated. Methods: The expressions of CD97, COX-2 and NF-kB in 47 cases of gastric MALT lymphoma were detected immunohistochemically, and the relevance between their expressions and the biological behavior was analyzed retrospectively. Results: 1) The expressions of CD97, NF-kB and COX-2 were 87.2%, 36.2% and 48.9%, respectively;2) The difference of CD97 expression between depth of invasion limited in mucosa and submucosa and beyond muscularis propria was significant (100.0% vs. 71.4%, P < 0.01). Moreover, the expression of nuclear CD97 between stage IIE, III, IV and stage I patients showed significant difference (96.4% vs. 73.7%, P < 0.05);3) The expression of NF-kB was significantly correlated with tumor size, depth of invasion and stage;4) The expression of COX-2 was significantly correlated with Helicobacter pylori infection, clinical stage, depth of invasion and tumor size (P < 0.05). Conclusions: Expressions of CD97, NF-κB and COX-2 were correlated with tumor invasion and metastasis in gastric MALT lymphoma.

CD97蛋白在胃黏膜相关淋巴组织淋巴瘤中的表达及意义

目的探讨CD97蛋白在胃黏膜相关淋巴组织淋巴瘤（MALT）中的表达及其临床意义。方法对47例胃MALT淋巴瘤石蜡切片进行免疫组织化学染色，分析CD97表达及与临床病理因素和生存时间之间关系。结果CD97在肿瘤中呈弥漫性表达，阳性表达率为87．2％：其中肿瘤浸润超过肌层病例表达率为100％，高于肿瘤局限于黏膜层或黏膜下层者的71．4％（P〈0．01）；Ⅱ、Ⅲ和Ⅳ期患者表达率为96．4％，显著高于Ⅰ期患者的73．7％（P〈0．05）；肿瘤大于5cm者表达率为96．4％，显著高于肿瘤小于或等于5cm者的73．7％（P〈0．05）。CD97强阳性表达者术后平均生存时间39．2个月，较非强阳性表达者（100．3个月）短（P〈0．01）。结论CD97在胃MALT淋巴瘤组织中高表达，且与肿瘤浸润转移和预后密切相关。

CD97异构体在结肠癌组织中的表达及其临床意义

目的研究CD97各异构体mRNA在结肠癌中的表达水平及其临床意义。方法收集2013年12月至2014年5月温州医科大学附属第一医院结肠癌患者50例,以及人结肠癌细胞株SW480和SW620。采用实时荧光定量聚合酶链反应检测CD97人类表皮生长因子(EGF)(1,2,5)、CD97EGF(1,2,3,5)、CD97EGF(1,2,3,4,5)mRNA在结肠癌、癌旁组织及正常结肠组织、SW480和SW620细胞中的表达情况,分析CD97EGF(1,2,5)mRNA表达与临床病理因素之间的关系。结果CD97异构体CD97EGF(1,2,5)、CD97EGF(1,2,3,5)、CD97EGF(1,2,3,4,5)mRNA相对表达量在癌组织中高,而在癌旁组织和正常组织少量表达,差异具有统计学意义(0.71±0.20比0.40±0.09比0.35±0.07,F=107.642,P<0.01;0.45±0.11比0.26±0.05比0.27±0.06,F=94.231,P<0.01;0.41±0.10比0.21±0.05比0.19±0.03,F=165.672,P<0.01)。不同肿瘤浸润深度(T1~T2和T3~T4)和临床分期(Ⅰ~Ⅱ和Ⅲ~Ⅳ)结肠癌患者CD97EGF(1,2,5)mRNA表达水平比较,差异均具有统计学意义(t=-2.582和t=-5.062,P=0.013和P<0.01)。在SW620细胞中CD97EGF(1,2,5)mRNA表达量高于SW480细胞。结论CD97异构体在结肠癌组织中高表达,CD97EGF(1,2,5)可能在结肠癌发展和浸润过程中起着重要作用。CD97异构体可能成为在结肠癌治疗的一个新标志物。

CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation

The G protein-coupled receptor ADGRE5(CD97)binds to various metabolites that play crucial regulatory roles in metabolism.However,its function in the antiviral innate immune response remains to be determined.In this study,we report that CD97 inhibits virus-induced type-I interferon(IFN-I)release and enhances RNA virus replication in cells and mice.CD97 was identified as a new negative regulator of the innate immune receptor RIG-I,and RIG-1 degradation led to the suppression of the IFN-I signaling pathway.Furthermore,overexpression of CD97 promoted the ubiquitination of RIG-I,resulting in its degradation,but did not impact its mRNA expression.Mechanistically,CD97 upregulates RNF125 expression to induce RNF125-mediated RIG-I degradation via K48-linked ubiquitination at Lys181 after RNA virus infection.Most importantly,CD97-deficient mice are more resistant than wild-type mice to RNA virus infection.We also found that sanguinarine-mediated inhibition of CD97 effectively blocks VSV and SARS-CoV-2 replication.These findings elucidate a previously unknown mechanism through which CD97 negatively regulates RIG-I in the antiviral innate immune response and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral agents.

EGF-TM7亚家族在消化系统肿瘤中的作用

EGF-TM7是一类特殊的G蛋白偶联受体,能同时介导黏附及跨膜信号转导,研究显示其表达与肿瘤侵犯、转移或不良预后等有关。其在消化系统肿瘤中以CD97及EMR2的异常表达为主,这为研究消化系统肿瘤提供了一种新的视角,并为早期诊断及治疗提供了新的可能。