Tumor growth inhibition effect of hIL-6 on colon cancer cells transfected with the target gene by retroviral vector

AIM To observe the tumor inhibitory effects bytransfecting IL-6 cDNA into colon cancer cell lineHT-29 with retroviral vector pZIP cDNA.METHODS Human IL-6 gene was reconstructedin retrovirus vector and transfected into incasingcells PA317 by lipofectamine mediated method,the clones of the cells transferred with hlL-6were selected by G418,and targeted HT-29 cellswere infected with the virus granules secretedfrom PA317 and also selected by G418.Test genetranscription and expression level byhybridization,ELISA and MTT assay,etc.Analyze tumor inhibitory effects according to thecell growth curve,plating forming rate andtumorigenicity in nude mice.RESULT Successfully constructed andtransfected recombinant expressing vectorspZIPIL-6 cDNA and got positive transfected celllines.The colon cancer cell line(HT-29 IL-5)transfected with the hlL-5 gene by retroviralvector was established.The log proliferationperiod and the doubling time of this cell line wasbetween 4 to 7 days and 2.5 days according tothe direct cell count,the cell proliferation wasobviously inhibited with MTT assay,the platinginhibitory rate was 50% by plating efficiencytest.When HT-29 IL-6 cells were inoculated intothe nude mice subcutaneously,carcinogenicactivity of the solid tumor was found superior tothe control group and the size of tumor was notsignificantly enlarged.Injection of combinationvirus fluid containing 11.-6 gene intotransplantation tumors could inhibit the growthand development of the tumor.CONCLUSION IL-6 could inhibit the growth andproliferation of colon cancer cells by retroviralvector-mediated transduction.

EFFECT OF TNF-a AND IFN-g ON THE EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE GENE AND PROLIFERATION INHIBITION OF HUMAN COLON CANCER CELL LINE

Objective: To study the expression of the inducible nitric oxide synthase (iNOS) gene and the effects of tumor necrosis factor-α(TNF-a) and interferon-γ(IFN-g)on proliferation of the continuous cultured human colon cancer cell line CCL229. Methods: Using the molecular and biochemical techniques and electron microscopy to analyze the expression of iNOS, production of NO and growth characteristics of human colon cancer cells. Results: cytokine treatment can induce expression of the iNOS gene and production of nitric oxide was significantly higher after treatment of CCL229 cells with TNF-αor IFN-γ. Treatment with either cytokine or a combination of both significantly increased levels of Malondialdehyde (MDA) over control. Furthermore, cytokine treatment increased the proliferation inhibition rate as assessed in vitro and decreased the cell proliferation index on flow cytometry. Electron microscopy showed that cells treated with cytokines had fewer pseudopodia or cell processes than control cells and that cytokine treated cells had dilatation of the mitochondria and endoplasmic reticulum and dilated vesicular or tubular cisternae. Conclusion: Our findings indicate that TNF-α and IFN-γ induce the expression of iNOS gene in CCL229 cells, which increases the production of nitric oxide, inhibits proliferation, causes lipid peroxidation, and results in ultrastructural changes.

The expression of HER-2/neu gene in colon cancer tissues and its clinical significance

Objective：The article aims to detect the expression of HER-2/neu gene in colon cancer tissues and adjacent tissues, to analyze the relationship between dif erent pathologic types and clinical features, also to invest the distribution of patients with positive expression of HER-2 gene. Methods：The expression of HER-2 gene in the 223 samples with colon can-cer was detected by immunochemical approach. The expression of HER-2 gene in colon cancer tissues and adjacent tissues and dif erent pathologic types was analyzed byχ2 test. The correlation between the expression of HER-2 gene and clinical features was analyzed by Spearman. Results：The number of positive expression of HER-2 gene in colon cancer tissues and adjacent tissues were 74 and 0 respectively, the dif erence has statistical significance. The number of papil ary or tubular adenocarcinoma was 182, among them, 60 cases were positive expression. The number of mucinous adenocarcinoma was 41, among them, 14 cases were positive expression. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, which has no statistical significance. However, the expression of HER-2/neu gene has correlation with metastasis of lymph node and Dukes stage, which has statistical significance. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The correlated coef icient index was 0.320 and 0.320 respectively. In the 74 patients with positive expression of HER-2 gene, 59.4%of them were 60-74 years old. And there was 97.3%of the patients without family history of adenocarcinoma. Conclusion：The expression of HER-2/neu gene in colon cancer tissues was higher than in adjacent tissues. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, but has correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene with age of 60-74 years old and without family history of adenocarcinoma was higher than other groups.

表达CD40L的小鼠结肠癌colon26瘤苗增强DC活性

目的:观察表达CD40L的小鼠结肠癌colon26瘤苗体内外对DC活性的影响。方法:以脂质体法将CD40L基因转染colon26细胞获得稳定表达CD40L的colon26/CD40L瘤苗。colon26/CD40L细胞与小鼠骨髓来源DC共培养,流式细胞术检测DC表型变化,RT-PCR法检测细胞因子基因P19、P35、P40、IL-18和IFN-γ的表达,ELISA法检测共培养上清中IL-12、IL-23和IFN-γ的水平。BALB/c小鼠皮下注射colon26细胞制备荷瘤小鼠模型,colon26/CD40L致敏DC治疗荷结肠癌小鼠,ELISA法检测荷瘤小鼠外周血中IL-12、IL-23、IFN-γ、IL-10和TGF-β的水平,H-E染色观察肝、脾和肿瘤组织的病理学变化。结果:成功获得高表达CD40L的丝裂霉素(MMC)处理的colon26/CD40L瘤苗。DC与colon26/CD40L瘤苗共培养后,DC表面共刺激分子CD80、CD86、MHCⅠ和MHCⅡ表达增高(P<0.01);共培养体系中可检测到P19、P35、P40、IL-18和IFN-γmRNA的表达,而在其他组未检测到上述基因的表达;共培养细胞上清中有较高水平的IL-12、IL-23和IFN-γ(P<0.01)。co-lon26/CD40L瘤苗致敏DC治疗组与colon26/CD40L瘤苗治疗组、DC治疗组比较,小鼠移植瘤的体积和质量明显减小和减少(P<0.05);小鼠外周血IL-12、IL-23和IFN-γ明显升高(P<0.01),IL-10和TGF-β明显降低(P<0.01);小鼠移植瘤组织病理变化显著减轻。结论:表达CD40L的丝裂霉素(MMC)处理的结肠癌瘤苗可促进DC的成熟,刺激DC分泌细胞因子,增强DC体内外活性,从而增强治疗体系的抗肿瘤免疫效应。

^(60)Co照射对Colon 26/IL-21细胞生长及其抗肿瘤效应的影响

目的探讨经高剂量同位素照射后肿瘤细胞(瘤苗)生长变化及其抑瘤效应。方法单次给予60Co50Gy照射转染IL-21的结肠癌细胞株Colon 26/IL-21制备瘤苗,MTT法及RT-PCR法测定细胞代谢活力变化、基因转录水平及凋亡率、细胞周期变化;采用细胞接种方法测定瘤苗成瘤情况,ELISA法测定共培养液中IFN-γ水平和抗肿瘤效应。结果瘤苗处于G1期的细胞在群体中明显增高,其细胞增殖指数明显下降,凋亡率明显增加;瘤苗保持较高的IFN-γ分泌水平,接种2×106/200μl后肿瘤细胞生长明显受抑。结论高剂量同位素照射可制备具有转基因生物学活性的瘤苗,其高剂量接种后具有抗肿瘤效应。

ANTITUMOR EFFECT OF INTRATUMORAL INJECTION OF LIPOSOME-ENCAPSULATED G-CSF GENE AND IN SITU BIOLOGICAL CHARACTERISTICS OF THE TREATED TUMOR CELLS

This word was supported by grant from Military Medical Research Foundation of china (96z032). ** To whom correspondence and requests for reprints should be addressed. This is one of papers of the special issue on gene therapy research (Chin J Cancer Res Vol. 9 No. 4 December, 1997). In order to investigate the antitumor effects of the in vivo G CSF gene therapy mediated by liposome and its mechanisms, human G CSF gene was encapsulated into liposome and was directly injected into tumor mass of C 26 colon adenocarcinoma bearing mice. After direct intratumoral injection of liposome encapsulated G CSF DNA, the subcutaneous tumor growth was dramatically inhibited and the survival time was prolonged signifi cantly. Tumor regression could be observed in about 30% of C 26 bearing mice. By the analysis of the antitumor mechanisms, we found that anti G 418 (600ug/ml) clone could be selected from the tumor cells freshly separated from the treated C 26 tumor mass, and secretion of G CSF in the supernatant could be detected. Northern blot also confirmed the expression of hG CSF by the tumor cells. Higher expressions of MHC class I(H 2k d) molecule and ICAM 1 on the tumor cells could be observed. The results demonstrated that liposome can effectively transfect G CSF gene into tumor cells in situ , and then increase the immunogenicity of the tumor cells which may contribute to the activation of the local antitumor immune responses effectively.

NQO1 C609T polymorphism correlated to colon cancer risk in farmers from western region of Inner Mongolia

Objective： To investigate the relationship between NAD（P）H：quinone oxidoreductase 1 （NQOI） C609T polymorphism and colon cancer risk in farmers from western region of Inner Mongolia. Methods： Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was performed to analyze NQO1 C609T polymorphism from 160 healthy controls and 76 colon cancer patients. Results： Among the colon cancer patients, the incidence of NQOI T allele （53.29%） was significantly higher than it in control group （33.75%, P〈0.001）. The individuals with NQO1 T allele had higher risk [2.239 （95% CI： 1.510-3.321） times] to develop colon cancer than individuals with NQO1 C allele. The incidence of NQO1 （TFI-） （34.21%） in colon cancer patients was higher than that in control group （15.62%, P〈0.001）. Odds ratios （OR） analysis suggested that NQO1 （T/F） and NQOI （T/C） genotype carriers had 3.813 （95% CI： 1.836-7.920） times and 2.080 （1.026-4.219） times risk compared with wild-type NQO1 （C/C） gene carriers in developing colon cancer. Individuals with NQO1 （T/I＇） genotype had 2.541 （95% CI： 0.990-6.552） times, 3.713 （95% CI： 1.542-8.935） times, and 3.471 （95% CI： 1.356-8.886） times risk than individuals with NQOI （T/C） or NQOI （C/C） genotype in well- differentiated, moderately-differentiated, and poorly-differentiated colon cancer patients, respectively. Conclusions： NQO1 gene C609T could be one of risk factors of colon cancer in farmers from western region of Inner Mongolia,

siRNA-targeted inhibition of growth hormone receptor in human colon cancer SW480 cells

AIM:To determine the effects of RNAi-mediated inhibition of the growth hormone receptor(GHR)gene on tumors and colon cancer cells in vivo.METHODS:Construction of a eukaryotic vector for human GHR expression,the pcDNA 6.2-GW/EmGFPsmall interfering RNAs(siRNAs)-GHR plasmid,was used to inhibit GHR expression.Thirty-six BALB/c nude mice were randomly divided into groups and treated with normal saline(NS),recombinant plasmid(G2),growth hormone(GH),5-fluorouracil(FU),G2+FU or G2+FU+GH.Each nude mouse was subcutaneously inoculated with 1×107human colon cancer SW480 cells;the nude mice were weighed before inoculation and on the 2nd,5th,8th,11th,14thand 17thday after inoculation.All nude mice were sacrificed after 17 d.Each subcutaneous tumor was removed and studied.Tumor volume was measured on the 5th,8th,11th,14thand 17thday after inoculation.The expression of GHR protein in the tumor tissue was detected by Western blotting analysis,and the differences in GHR mRNA expression in the tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS:Compared to the control group,the weights of the inoculated nude mice on the 17thday after inoculation were:G2:21.60±0.71 g,GH:21.64±0.45 g,FU:18.94±0.47 g,FU+G2:19.40±0.60 g,G2+FU+GH:21.04±0.78 g vs NS:20.68±0.66 g,P<0.05;the tumor volumes after the subcutaneous inoculation were:G2:9.71±3.82 mm3,FU:11.54±2.42mm3,FU+G2:11.42±1.11 mm3,G2+FU+GH:10.47±1.02 mm3vs NS:116.81±10.61 mm3,P<0.05.Compared to the GH group,the tumor volumes were significantly decreased in the experimental groups.The GHR protein expression(G2:0.39±0.02,FU:0.40±0.02,FU+G2:0.38±0.01,G2+FU+GH:0.39±0.01 vs NS:0.94±0.02,P<0.05)and the GHR mRNA expression(G2:14.12±0.10,FU:15.15±0.44,FU+G2:16.46±0.27,G2+FU+GH:15.37±0.57 vs NS:12.63±0.14,P<0.05)were significantly decreased and increased,respectively,in the experimental groups.CONCLUSION:Inhibition of GHR in human colon cancer SW480 cells resulted in anti-tumor effects in nude mice.

THE THERAPEUTIC EFFECT OF INTRATUMORAL INJECTION OF GM-CSF GENE-MODIFIED ALLOGENIC MACROPHAGES ON TUMOR-BEARING MICE

Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GMCSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GMCSF genemodified allogenic macrophages on tumorbearing mice observed. The peritoneal macrophages of C57BL/6 mice were transfected with GMCSF gene mediated by recombinant adenovirus and the subcutaneous CT26 colon adenocarcinomabearing BALB/c mice were treated by intratumoral injection of the above macrophages. The survival time of the tumorbearing mice were prolonged significantly and some tumor mass disappeared completely. The necroses of the tumor cells and massive infiltration of inflammatory cells were observed 6 days after treatment. 30 days after treatment, only the leftover of tumor cells and the inflammatory cells remained. The data indicated that introtumoral injection of GMCSF genemodified allogenic macrophages displayed more potent therapeutic effect on the preestablished tumorbearing mice.

基于机器学习构建新型结肠癌免疫评分模型

目的:基于免疫相关基因,利用机器学习方法构建结肠癌免疫评分模型,用于评估患者的生存状态和免疫治疗效果。方法:使用Lasso+bootstrap+多因素Cox的组合策略,基于1 301个免疫相关基因在结肠癌中的表达情况,对TCGA中的结肠癌患者进行免疫相关基因(IRG)评分,并对高/低分组在功能差异、预后状态、免疫治疗相关等方面进行比较。结果:基于IRG评分的分组在结肠癌患者预后状态方面具有显著差异,并且通过其他独立数据集的验证,IRG评分模型同时能够评估结肠癌患者的免疫治疗效果。结论:本研究能为基于免疫基因的结肠癌免疫治疗和研究提供思路,IRG评分模型可以用于评估结肠癌患者的预后情况。

外源抗生素抗性基因在农田系统中的定殖机制综述

外源抗生素抗性基因(Antibiotic resistance genes,ARGs)对土壤生态健康和农产品质量安全构成严重威胁,但ARGs在土壤-农作物系统中定殖机理不清、跨界迁移机制不明,直接制约了农业系统中细菌耐药污染的有效防控。本文简要论述农田系统ARGs目前赋存现状,系统综述外源ARGs在农田土壤和农作物中的动态演变特征及其与土壤特性的关联性,梳理了ARGs在土壤中侵入-持留-迁移的定殖分子机制以及揭示耐药菌与内生菌之间的交互过程及驱动因素,并提出关于未来农田ARGs环境行为和阻控研究的展望和建议。

SNHG7对结肠癌预后影响的生物信息学分析

目的研究长链非编码RNA(lncRNA)核仁小RNA宿主基因7(SNHG7)的表达程度与结肠癌预后的关系,以期寻找一种新型潜在的结肠癌标记物及治疗新靶点。方法从癌症基因组图谱(TCGA)数据库下载所有结肠癌转录数据,提取其中表达SNHG7的数据并整理成矩阵资料,利用R软件对数据进行分析,通过SNHG7差异性表达,生存分析、受试者工作特征曲线(ROC曲线),单因素多因素独立预后分析及结合临床数据特征探讨SNHG7与结肠癌患者预后的相互联系。结果SNHG7在结肠癌标本中高表达,SNHG7高表达组与SNHG7低表达组相比总体生存率明显降低,单因素及多因素回归分析显示SNHG7可作为结肠癌患者预后不佳的独立危险因素(P<0.05)。临床数据相关性研究提示SNHG7的表达量与SNHG7甲基化程度相关,SNHG7甲基化程度与结肠癌的N分期、种族相关(P<0.05)。结论SNHG7为结肠癌患者预后差的危险因素,可以作为结肠癌患者诊断和预后的潜在标志物,并为治疗结肠癌靶点提供新方向。

结直肠癌组织中lncRNA CCAT2和NDRG1的表达及意义

目的探讨结直肠癌(CRC)患者组织中长链非编码RNA(lncRNA)结肠癌相关转录物2(CCAT2)、N-myc下游调节基因(NDRG)1的表达及与临床病理特征及预后的关系。方法选取2018年2月至2020年2月在南通市中医院行CRC根治性手术治疗的96例CRC患者作为研究对象。采用实时荧光定量PCR检测组织中lncRNA CCAT2、NDRG1 mRNA表达,采用免疫组织化学检测组织中NDRG1蛋白表达,采用Kaplan-Meier曲线分析不同lncRNA CCAT2、NDRG1 mRNA表达组患者的预后差异,采用多因素Cox回归分析CRC预后影响因素。结果与癌旁组织比较,癌组织中lncRNA CCAT2表达较高,NDRG1 mRNA表达及蛋白阳性率较低,差异有统计学意义(P<0.05)。与TNM分期Ⅰ~Ⅱ期、无淋巴结转移比较,TNM分期Ⅲ期、有淋巴结转移的CRC患者癌组织中lncRNA CCAT2表达较高,NDRG1 mRNA表达较低(P<0.05)。lncRNA CCAT2高表达组3年累积生存率低于lncRNA CCAT2低表达组,而NDRG1 mRNA高表达组3年累积生存率高于NDRG1 mRNA低表达组,差异有统计学意义(P<0.05)。TNM分期、淋巴结转移,lncRNA CCAT2、NDRG1 mRNA是CRC预后影响因素(P<0.05)。结论CRC组织中lncRNA CCAT2表达升高,NDRG1表达降低,二者均参与CRC肿瘤的进展,可作为评估CRC患者生存预后的新指标。

ecp基因簇在路德维希肠杆菌AA4定殖松材线虫中的功能研究

松材线虫病生防细菌路德维希肠杆菌EnterobacterludwigiiAA4能够有效地定殖并杀死松材线虫。大肠杆菌共有型菌毛(Escherichia coli common pilus,ECP)在动植物共生与病原细菌中普遍存在,能够通过增强细菌与宿主细胞之间及生物膜群落中细菌之间的相互作用,提高共生与病原细菌的定殖能力。大肠杆菌共有型菌毛由ecp基因簇编码。为了探究ecp基因簇在菌株AA4定殖松材线虫中的功能,本研究通过BLAST比对分析,鉴定了菌株AA4中的ecp基因簇;利用Red重组技术构建了菌株AA4的ecp基因簇缺失突变体,并对上述突变体定殖松材线虫的能力与定殖相关表型进行了分析。研究结果表明,ecp基因簇缺失突变体菌毛装配能力显著减弱,运动性、生物膜形成能力以及在松材线虫上的定殖能力显著降低。因此,AA4的ecp基因簇可能通过调节菌毛装配,影响其运动性与生物膜形成能力,进而实现对菌株AA4定殖松材线虫的调控。上述研究结果将为揭示松材线虫病生防路德维希肠杆菌AA4定殖松材线虫的分子机制奠定理论基础,为松材线虫病生防微生物制剂的研发与高效应用提供科学依据。

SOX4靶向miR-17对结肠癌细胞HCT-116生物学行为的影响

目的探讨性别决定区Y框蛋白4(SOX4)及miR-17在结直肠癌中的表达及对HCT-116细胞生物学行为的作用。方法收集2020年3月至2022年1月在河北北方学院一附院和张家口市第一医院的27例结直肠癌患者组织标本并检测SOX4及miR-17的表达水平,并分析与临床病理特征的关系。利用慢病毒转染技术干预HCT-116细胞的SOX4及miR-17表达。检测各组细胞中SOX4和miR-17的表达及细胞增殖、侵袭、迁移能力、细胞活性变化和相关蛋白表达。结果与正常组织比较,结直肠癌组织中SOX4表达水平升高。SOX4及miR-17在结直肠癌组织中的表达呈正相关(r=0.724,P<0.001),SOX4和miR-17的表达和病理分期、淋巴结转移、肝转移情况相关,差异有统计学意义(P<0.05),而与肿瘤的大小、分化程度无相关(P>0.05)。SOX4模拟组细胞增殖能力、迁移能力及细胞活性显著高于对照组及SOX4抑制剂组(P<0.05)。SOX4抑制剂组与对照组相比迁移及增殖相关蛋白表达差异有统计学意义(P<0.05)。结论SOX4在结直肠癌组织中表达上调,SOX4的表达可促进结肠癌细胞增殖、迁移和侵袭能力,miR-17可能是其下游调控靶点。

着丝粒蛋白U在结直肠癌患者肠组织中的表达情况及临床意义

目的旨在探讨着丝粒蛋白U(centromere protein U,CENPU)在结直肠癌患者肠组织中的表达情况,并结合生物信息学分析其表达水平对结直肠癌患者预后的影响。方法通过实时荧光定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)、蛋白质免疫印迹(Western blot,WB)法以及免疫组织化学染色(immunohistochemistry,IHC)实验验证CENPU在组织中的表达情况。结合患者临床病例资料,通过单因素和多因素Cox回归分析CENPU的表达与结直肠癌患者临床病例参数的相关性;然后通过绘制受试操作者操作特征(receiver operating characteristic,ROC)曲线和Kaplan-Meier生存曲线,探究CENPU的表达对结直肠癌患者预后的预测作用。最后,通过生物信息学分析CENPU的表达对结直肠癌疾病进展影响的可能分子机制。结果通过qRT-PCR、WB法以及IHC实验均发现,与正常组织比较,CENPU在结直肠癌患者癌组织中表达显著升高。Cox回归分析表明CENPU的表达与患者的年龄和TNM分期显著相关,是影响患者预后的危险因素。Kaplan-Meier生存曲线分析表明:CENPU高表达的结直肠癌患者的生存率显著降低。ROC曲线结果表明:基于CENPU的表达建立的模型具有较高的预测结直肠癌患者预后的能力。生物信息学分析结果表明:CENPI、CENPN、CENPD、CENPK、CENPP、CENPM、CENPQ、CENPH、NDC80以及ITGB3BP这10个基因与CENPU基因具有相互作用关系;CENPU参与DNA修复、MYC/TARGETS/V1以及PI3K/AKT/MTOR等信号通路。结论结直肠癌患者癌组织中高表达的CENPU与患者的不良预后显著相关,提示CENPU有望成为结直肠癌患者早期诊断及预测预后的潜在靶点。

基于TCGA数据库分析参与结肠癌进展的关键基因

目的通过生物信息学方法与实验验证挖掘结肠癌发生发展中的关键基因,预测可用于诊断结肠癌(colorectal cancer,CRC)的生物标志物。方法从TCGA数据库中获取结肠癌转录组数据,用edgR,Deseq2和limma3个R包分析癌组织与癌旁组织的差异性,将得到的差异基因进行Gene Ontology(GO)和Kyoto Encyclopedia of Genes and Genomes(KEGG)分析。通过STRING数据库构建蛋白-蛋白互作网络后,置于Cytoscape软件中进行可视化及核心基因筛选。利用R包对核心基因进行Kaplan-Meier单因素生存分析,通过qRT-PCR对13对结肠癌及配对癌旁组织中各核心基因的表达进行检测。结果研究共获得1645个差异基因,其中712个上调,933个下调。上调基因主要富集在类风湿性关节炎、IL-17信号通路、细胞因子-细胞因子受体相互作用、Wnt信号通路、Hippo信号通路。下调基因主要富集在矿物质吸收、神经活性配体-受体相互作用、CAMP信号通路、胆汁分泌、碳酸氢盐在肾单位近曲小管重吸收等通路。研究共获得10个核心基因:CXCL8、CXCL1、CXCL12、CXCL5、CSF2、CXCL2、CXCL3、CXCL11、CCL19和CCL13。生存分析显示CXCL8、CXCL5、CSF2、CCL13、CCL19、CXCL12与结肠癌预后相关,qRT-PCR检测结果证实CXCL8、CXCL5和CSF2结肠癌及癌旁组织中的表达有明显差异。结论结肠癌发生发展过程中CXCL8、CXCL5和CSF2基因存在表达变化,可能在结肠癌的发生发展中起关键作用。

加权基因共表达网络分析结肠癌免疫相关生物标志物

目的旨在鉴定可能参与结肠癌发生发展的免疫相关预后基因,采用加权基因共表达网络对癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)联合分析,筛选免疫生物标志物。方法2022年11月至12月,对GSE41657数据集和TCGA结肠癌数据集中免疫相关基因进行加权基因共表达网络分析,并从关键模块筛选免疫相关生物标志物,利用TCGA数据库中基因表达数据和临床信息进一步分析。结果获得了结肠癌发生发展中与免疫相关的最关键模块,其功能富集到免疫细胞趋化、游走、活化、增殖、迁徙等,通路富集到趋化因子信号通路、抗原处理和呈递、MAPK信号通路、HIF-1信号通路、PI3K-Akt信号通路、NF-kappa B信号通路等。找到了有望作为结肠癌预后靶点的10个基因:NMB、SCG2、IL1A、ULBP2、INHBB、COLEC12、F2RL1、ANGPTL1、NR3C2、TNFRSF17。通过TIMER数据库筛选出2个与结肠癌免疫相关性最为密切的基因——COLEC12、ANGPTL1,这两个基因富集到诸多免疫相关和癌症相关通路——JAK Stat信号通路、Toll样受体信号通路、MAPK信号通路等,可能在肿瘤免疫微环境中发挥重要作用。结论COLEC12、ANGPTL1可能通过多种信号通路对结肠癌及其免疫微环境进行调控,有望成为潜在的免疫治疗靶点。