ZEB1-AS1在结肠癌中表达及与铂类药物化疗敏感性的关系

目的 探讨结肠癌组织中锌指E-盒结合同源异形盒(ZEB)1-反义链(AS)1的表达及其与铂类药物化疗敏感性的关系。方法 选取结肠癌患者120例为研究组，收集患者手术过程中切除的癌组织及癌旁正常组织，实时荧光定量(qRT)-PCR法检测癌组织及癌旁组织中ZEB1-AS1的表达情况；分析ZEB1-AS1高低表达与临床病理特征的相关性；分析ZEB1-AS1高低表达与铂类化疗客观有效率的关系；Kaplan-Meier法分析ZEB1-AS1与5年生存期的关系；Cox回归模型分析影响患者预后不良的因素。结果 研究组ZEB1-AS1水平高于对照组，差异有统计学意义(P<0.05)。结肠癌患者ZEB1-AS1表达与年龄、性别、肿瘤直径不相关(P>0.05),与TNM分期、淋巴结转移相关(P<0.05)。ZEB1-AS1低表达患者治疗有效率显著高于ZEB1-AS1高表达患者(P<0.05)。Kaplan-Meier分析结果显示，ZEB1-AS1高表达患者5年生存率显著低于ZEB1-AS1低表达患者(P<0.05)。多因素Cox分析显示，TNM分期Ⅳ期、淋巴结转移、化疗无效、...     

长链非编码RNA ZNF667-AS1在非小细胞肺癌组织中表达上调

目的:探讨非小细胞肺癌（NSCLC）组织中长链非编码RNA（lncRNA） 锌指蛋白667反义RNA1（ZNF667-AS1）的表达水平。方法： 97例NSCLC患者被纳入本研究，术中留取新鲜的癌组织及对应癌旁组织，采用实时定量聚合酶链式反应（PCR）法检测lncRNA ZNF667-AS1和血管内皮生长因子（VEGF）的表达，分析lncRNA ZNF667-AS1的表达与NSCLC患者临床病理特征的关系，绘制受试者工作特征（ROC）曲线，评估lncRNA ZNF667-AS1用于诊断NSCLC的价值，分析癌组织中VEGF的表达与lncRNA ZNF667-AS1表达的相关性。结果：PCR检测结果显示，97例NSCLC患者癌组织中lncRNA ZNF667-AS1的平均相对表达量明显高于癌旁组织（P<0.05）。不同性别、年龄、肿瘤直径及病理组织类型的NSCLC患者癌组织中lncRNA ZNF667-AS1相对表达量比较，差异无统计学意义（P均＞0.05），但不同组织分化程度、临床分期、浸润程度及有无淋巴结转移的患者癌组织中lncRNA ZNF667-AS1相对表达量比较，差异有统计学意义（P均<0.05）。实时荧光定量PCR检测结果显示，NSCLC癌组织中VEGF的相对表达量明显高于癌旁组织（P<0.01），NSCLC癌组织中lncRNA ZNF667-AS1的相对表达量与VEGF的表达呈正相关（P<0.05）。由ROC曲线可知，lncRNA ZNF667-AS1诊断NSCLC的AUC为0.792（95%CI：0.683-0.911，P﹤0.05），特异性为81.23%，敏感度为86.12%。结论： lncRNA ZNF667-AS1在NSCLC组织中表达上调，其可能作为一种促癌因子参与NSCLC的发生发展过程。     

LOXL2在胃癌组织中表达及其与PCNA、CyclinD1、MMP-2、MMP-9的关系

目的观察在胃癌组织中赖氨酰氧化酶(LOXL)2的表达变化,探讨其与增殖细胞核抗原(PCNA)、细胞周期素(Cyclin)D1、基质金属蛋白酶(MMP)-2、MMP-9及预后的关系。方法应用免疫组化法检测100例胃癌组织及相应癌旁正常胃组织中的LOXL2、PCNA、Cyclin D1、MMP-2、MMP-9蛋白表达,分析其在胃癌组织中表达与LOXL2的相关性。结果胃癌组织与癌旁正常胃组织相比,LOXL2、PCNA、Cyclin D1、MMP-2、MMP-9蛋白的水平明显增高(P0.05);在胃癌组织中LOXL2、PCNA、Cyclin D1、MMP-2、MMP-9蛋白阳性表达与肿瘤侵犯深度、淋巴结转移、TNM分期密切相关(P0.05),而与肿瘤大小、肿瘤分化程度及患者年龄无关(P0.05);经Kaplan-Meier生存分析得出结果,胃癌患者中LOXL2蛋白表达阳性者的生存率均明显低于阴性者(P0.01);经相关性分析发现,LOXL2与PCNA、Cyclin D1、MMP-2、MMP-9蛋白表达具有正相关性(r=0.279,0.287,0.402,0.453;均P0.01)。结论在胃癌组织中LOXL2高表达,可能与PCNA、Cyclin D1、MMP-2、MMP-9具有协同促进作用,提高了胃癌发生发展、侵袭转移概率,可能是影响预后的危险因素。     

circCSPP1在胃癌组织中的表达水平及其对胃癌患者的预后价值

目的 分析circCSPP1在胃癌及癌旁组织中的表达水平,并探讨其与胃癌临床病理特征和患者预后的关系。方法 收集2018年1月至2020年1月在我院接受根治性切除术治疗的胃癌患者118例,检测癌组织及癌旁组织circCSPP1表达水平,评价circCSPP1表达水平与胃癌患者临床病理资料相关性,Kaplan-Meier曲线分析circCSPP1表达水平与患者生存率关系;Cox回归分析评价影响胃癌患者预后的因素。结果 circCSPP1在TNM分期为Ⅰ～Ⅱ期、Ⅲ～Ⅳ期胃癌组织及癌旁组织中相对表达水平分别为2.08±0.17、3.29±0.27、1.01±0.12,即在胃癌组织中表达显著上调(F=4.292,P=0.005)。circCSPP1在胃癌组织中表达水平与肿瘤直径、浸润深度、TNM分期、淋巴结转移和其他器官转移有关(P<0.05)。circCSPP1低表达组患者生存率显著高于circCSPP1高表达组患者(χ²=5.332,P<0.05)。单因素Cox回归分析表明,胃癌组织中肿瘤直径≥5 cm、浸润深度T₃～T_4<...     

NSCLC组织SFRP1和β-连环蛋白表达与临床病理特征

目的分析非小细胞肺癌(NSCLC)组织分泌型卷曲相关蛋白1(SFRP1)和β-连环蛋白(β-catenin)表达与临床病理特征及预后的相关性。 方法选取2018年1月至2020年1月收治的35例NSCLC患者,采集患者癌组织和癌旁组织标本。采用免疫组化技术检测癌组织和癌旁组织中SFRP1、β-catenin表达,分析NSCLC患者癌组织SFRP1、β-catenin表达与病理特征的关系,癌组织SFRP1、β-catenin表达与预后的相关性。 结果癌组织SFRP1阳性表达率低于癌旁组织(P<0.05),癌组织β-catenin阳性表达率高于癌旁组织(P<0.05);NSCLC患者癌组织SFRP1、β-catenin表达与分化程度、淋巴结转移、临床分期有关(P<0.05)。35例NSCLC患者总生存率为58.82%,癌组织SFRP1阳性、阴性表达患者生存率分别为84.62%和45.450%,癌组织SFRP1阳性表达与阴性表达患者的生存曲线比较,差异有统计学意义(χ²＝5.221,P＝0.022);癌组织β-catenin阳性、阴性表达患者生存率分别为51.72%和100.00%。癌组织β-catenin阳性表达与阴性表达患者的生存曲线比较,差异有统计学意义(χ²＝4.828,P＝0.028)。 结论NSCLC组织SFRP1、β-catenin表达与分化程度、淋巴结转移、临床分期有关,临床检测癌组织SFRP1、β-catenin表达可用于非小细胞肺癌患者预后评估。     

胃肠胰神经内分泌肿瘤组织lncRNA HNF1A-AS1表达变化及其与患者预后的关系

目的 观察胃肠胰神经内分泌肿瘤(GEP-NENs)组织长链非编码RNA(lncRNA)肝细胞核因子1α-反义链1(HNF1A-AS1)表达变化,并分析其表达与患者预后的关系.方法 选择GEP-NENs患者85例,取手术切除的GEP-NENs组织及其配对的癌旁正常组织,采用RT-qPCR技术检测lncRNA HNF1A-AS1表达.比较GEP-NENs组织与癌旁正常组织lncRNA HNF1A-AS1表达差异,并分析lncRNA HNF1A-AS1表达与GEP-NENs患者临床病理特征的关系.以GEP-NENs组织lncRNA HNF1A-AS1相对表达量的均数为截断值,将患者分为lncRNA HNF1A-AS1高表达者与lncRNA HNF1A-AS1低表达者,比较不同lncRNA HNF1A-AS1表达的GEP-NENs患者3年累积生存率差异.采用Cox比例风险回归模型分析GEP-NENs患者预后不良的危险因素.结果 GEP-NENs组织lncRNA HNF1A-AS1相对表达量明显低于癌旁正常组织(P<0.01).lncRNA HNF1A-AS1表达与TNM分期、浸润深度、淋巴结转移有关(P均<0.05),而与性别、年龄、肿瘤直径、肿瘤部位无关(P均>0.05).lncRNA HNF1A-AS1高表达者41例、lncRNA HNF1A-AS1低表达者44例,lncRNA HNF1A-AS1高表达者3年累积生存率明显高于lncRNAHNF1A-AS1低表达者(P<0.01).多因素Cox比例风险回归分析显示,TNM分期Ⅲ、Ⅳ期和有淋巴结转移是GEP-NENs患者预后不良的危险因素,而lncRNA HNF1A-AS1高表达是其保护因素(P均<0.05).结论 GEP-NENs组织lncRNA HNF1A-AS1低表达,其表达变化与TNM分期、浸润深度和淋巴结转移有关;lncRNA HNF1A-AS1高表达是GEP-NENs患者预后的保护因素.     

FoxM1和COX-2在肺腺癌组织及癌旁组织中的表达及临床意义分析

目的分析叉头蛋白转录因子M1(FoxM1)和环氧合酶2(COX-2)在肺腺癌组织、癌旁组织中的表达及与病理特征、预后的关系。方法研究标本来源于我院病理科2015年1月~5月的存档蜡块,包括60份肺腺癌组织和35份癌旁正常肺组织,以标准化亲和素-生物素-过氧化物酶免疫组织化学法检测FoxM1和COX-2表达情况,Spearman等级相关性分析二者的相关性,借助χ^2检验分析其与病理特征的关系,以Kaplan—Meier法分析生存情况,并以COX回归模型分析预后的影响因素。结果FoxM1、COX-2在肺腺癌组织中阳性表达率分别为58.33%、68.33%,明显高于癌旁组织的17.14%、28.57%(χ^2=15.288,14.056,P<0.05)。肺腺癌组织中FoxM1与COX-2表达无明显相关性(P>0.05)。性别、年龄、癌变位置、肿瘤直径及是否吸烟与FoxM1、COX-2表达均无明显相关性(P>0.05),TNM分期、淋巴结转移与FoxM1、COX-2表达有关(P<0.05)。随访至少48个月,FoxM1阳性、阴性表达者生存率分别为48.57%、80.00%,COX-2阳性、阴性表达者生存率分别为43.24%、84.21%,均有统计学差异(log-rankχ^2=6.094,5.978,P<0.05)。TNM分期(HR=4.118)、淋巴结转移(HR=1.956)、FoxM1(HR=2.063)和COX-2(HR=1.467)阳性是肺腺癌预后的影响因素(P<0.05)。结论肺腺癌组织中FoxM1、COX-2表达增高,且与肿瘤进展、淋巴结转移及预后有关,但二者可能不存在协同作用。     

NOX1在结肠癌中的表达及临床意义

目的:探讨尼克酰胺腺嘌呤二核苷酸磷酸氧化酶1(NOX1) mRNA及蛋白在结肠癌组织中的表达情况及其与临床病理参数、预后的相关性。方法:选取126例结肠癌患者作为研究对象,留取癌组织及其癌旁组织。采用实时荧光定量PCR法检测NOX1 mRNA表达水平,免疫组织化学法检测NOX1蛋白表达情况;Ualcan数据库检索NOX1 mRNA及蛋白在结肠癌中的表达情况;分析结肠癌患者NOX1 mRNA及蛋白表达水平与预后的关系;分析影响结肠癌预后的因素。结果:Ualcan数据库中,TCGA数据集显示结肠癌组织NOX1 mRNA水平明显高于正常结肠组织(P<0.05),CPTAC数据集显示结肠癌组织NOX1蛋白水平与正常结肠组织比较差异无统计学意义。结肠癌患者癌组织NOX1 mRNA水平及蛋白阳性表达率明显高于癌旁组织(P<0.05)。结肠癌患者癌组织NOX1 mRNA及蛋白表达水平与肿瘤直径、淋巴结转移、TNM分期、分化程度有关(P<0.05)。NOX1 mRNA高表达结肠癌患者5年生存率明显低于NOX1 mRNA低表达患者(χ²=13.098,P<0...     

Copines-1与胃癌患者临床病理特征及疾病预后的关系

目的 探讨Copines-1(CPNE1)在胃癌(GC)患者不同临床病理特征中表达情况及与预后的相关性。方法 选取我院收治的102例GC患者为研究对象,采用免疫组化法比较肿瘤组织和癌旁正常组织CPNE1表达情况,并根据肿瘤组织免疫组化评分平均值将患者分为高表达组和低表达组,分析不同临床特征患者CPNE1蛋白表达情况;采用K-M生存曲线和COX比例风险回归法评估CPNE1蛋白和临床病理特征与总生存期相关性。结果 102例肿瘤组织中,共65例呈CPNE1高表达。肿瘤组织和癌旁组织评分分别为174.76±57.63和114.37±22.98,两组比较差异具有统计学意义(t=9.830,P<0.001)。临床特征亚组分析结果显示,TNM分期、淋巴结转移、血管侵犯中CPNE1蛋白表达具有统计学差异(P<0.05)。K-M生存分析结果显示CPNE1高表达、年龄≥66岁、TNM分期为Ⅲ-Ⅳ、有淋巴结转移、有血管侵犯、有神经侵犯的患者累积生存率更低;而COX分析结果显示,CPNE1高表达、有血管侵犯是患者不良预后的危险因素(P<0.05)。结论 CPNE1在GC组织中呈过表达,并与不...     

胃癌组织中Kiss-1 mRNA与Notch1 mRNA的表达及意义

目的探讨Kiss-1 mRNA与Notch1 mRNA在胃癌组织中的表达及意义。方法采用实时荧光定量聚合酶链反应检测胃癌和癌旁正常组织中Kiss-1 mRNA与Notch1 mRNA的表达情况,分析其与临床病理特征之间的关系。结果 Kiss-1 mRNA在胃癌组织中的表达较癌旁正常组织中降低(P0.05);Kiss-1 mRNA的表达与胃癌的淋巴结转移、TNM分期密切相关(P0.05),与胃癌的浸润深度、分化程度、远处转移无关(P0.05);Notch1 mRNA在胃癌组中的表达较癌旁正常组织升高(P0.05);Notch1 mRNA的表达与胃癌的淋巴结转移、TNM分期、分化程度密切相关(P0.05),与胃癌的浸润深度、远处转移无关(P0.05)。结论 Kiss-1在胃癌的发病过程中发挥抑癌基因作用,并通过抑制转移来影响胃癌的预后;Notch1在胃癌的发病过程中发挥癌基因作用,有潜力成为早期诊断胃癌的新型肿瘤标记物。     

胃癌组织SDF-1、MRP1表达与临床病理参数的相关性分析

目的 探讨胃癌组织基质细胞衍生因子1(SDF-1)、多重耐药蛋白1(MRP1)表达与临床病理参数的相关性.方法 选取2017年6月至2018年6月邯郸市中心医院收治的胃癌患者50例,采用免疫组化法检测正常胃黏膜组织、胃癌组织及其癌旁组织SDF-1、MRP1的表达,分析胃癌组织SDF-1、MRP1与临床病理参数的相关性....     

Low expression of long non-coding RNA ARAP1-AS1 can inhibit lung cancer proliferation by inducing G0/G1 cell cycle organization

BackgroundThis paper examines the expression, function, and molecular mechanism of long non-coding ribonucleic acid (lncRNA) ARAP1 antisense RNA 1 (ARAP1-AS1) in lung cancer. Specifically, it aims to clarify the molecular mechanism of lncRNA ARAP1-AS1 that affects the occurrence and development of lung cancer, and provide a theoretical basis and molecular targets for targeted therapy or early diagnosis of lung cancer.MethodsFluorescence quantitative detection of lncRNA ARAP1-AS1 expression in lung cancer tissues and cell lines, and methylthiazolyldiphenyl-tetrazolium (MTT), plate cloning experiment, and flow cytometry were used to detect the effect of knockdown of lncRNA ARAP1-AS1 on cell proliferation, clone formation, and the cell cycle, respectively. Western blotting was used to detect the expression of cell cycle-related proteins as well as the effect of knockdown of lncRNA ARAP1-AS1 on lung cancer. Cell proliferation was assessed by a nude mouse subcutaneous tumor formation experiment.ResultsLncRNA ARAP1-AS1 is highly expressed in lung cancer tissues and cells. Knockdown of LncRNA ARAP1-AS1 can significantly inhibit the proliferation and clonal formation of lung cancer cells and induce G0/G1 cell cycle arrest. Knockdown of ARAP1-AS1 can markedly inhibit the expression of cell cycle-related protein cyclin D1, but has no significant effect on the expression of cyclin-dependent kinase (CDK)4 and CDK6. Furthermore, knockdown of ARAP1-AS1 can also notably inhibit the growth of lung cancer cells and substantially reduce the expression of Ki-67 in tumor-bearing tissues in nude mice.ConclusionsLncRNA ARAP1-AS1 is highly expressed in lung cancer. Knocking down of this gene can significantly inhibit cell proliferation in vitro and in vivo, and can also cause G0/G1 cell cycle arrest by inhibiting the expression of cyclin D1.     

Original article: The expression of CFL1 and N‐WASP in esophageal squamous cell carcinoma and its correlation with clinicopathological features

Cofilin1 (CFL1) is an actin‐modulating protein, which belongs to the ADF/Cofilin family. Neural Wiskott–Aldrich syndrome protein (N‐WASP) is the key regulator of the actin cytoskeleton, a member of Wiskott‐Aldrich syndrome protein family. They have been suggested to be involved in cancer cell invasion and metastasis. In this study, the expression patterns of CFL1 and N‐WASP in normal esophageal mucosa and esophageal squamous cell carcinoma (ESCC) and their correlation with clinical characteristics were investigated. Immunohistochemical staining showed that CFL1 was expressed in nuclear and cytoplasm of cancer cells. However, N‐WASP was mainly found in the cytoplasm of the cancer cells. There were significant evidences that proved that CFL1 is correlated with clinicopathological factors in ESCC, such as infiltration depth, lymph node metastasis and pathological staging (P < 0.05). It is also proved that N‐WASP is related to lymph node metastasis and pathological staging in ESCC (P < 0.05). Kaplan–Meier analysis showed that there was no correlation between CFL1 and N‐WASP protein expression and survival (P > 0.05). Moreover, the mRNA expression of CFL1 and N‐WASP was detected by quantitative real time PCR in 70 tissue specimens. The results showed that CFL1 mRNA level was over‐expressed in ESCC tissue (P < 0.05), while N‐WASP mRNA expression level was not different between cancerous tissues and adjacent normal esophageal mucosa (P > 0.05). Also, CFL1 mRNA expression was significantly associated with regional lymph node metastasis and pathological staging (P < 0.05). Kaplan–Meier analysis showed that there was no correlation between CFL1 and N‐WASP mRNA expression and survival (P > 0.05). Our findings suggested that CFL1 and N‐WASP may play an important role in the tumorigenesis of ESCC, and to be the candidate novel biomarkers for the diagnosis and prognosis of ESCC. These findings may have implications for targeted therapies in patients with ESCC.     

Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract

AIM: To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 (HAI-1) in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis. METHODS: Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAM in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated. RESULTS: In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues (Z=-3.280, P= 0.006; Z=-4.651, P=0.000). HAI-1:SNC19/matriptase ratio showed no difference between normal and malignant tissues (P>0.05). Analysis of clinicopathological parameters showed decreased expression of HAM and HAI-1:SNC19/ matriptase ratio associated with stage Ⅲ/Ⅳ gastric tumors as compared to stage Ⅰ/Ⅱ ones (Z = -2.140, P= 0.031; Z= -2.155, P= 0.031), and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones (Z= -2.081, P= 0.036; Z= -2.686, P= 0.006). The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis (P>0.05). The expression of HAM and HAM:SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance (P>0.05). The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status (P>0.05). In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues (Z=-3.100, P=0.002; Z=-2.731, P=0.006), whereas HAI-1:SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance (P>0.05). The difference of SNC19/matriptase expression and HAI-1: SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status (P>0.05). The expression of SNC19/matriptase, HAI-1 or HAI-1: SNC19/matriptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status (P>0.05). CONCLUSION: The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.     

基于Oncomine及TCGA数据集分析结肠肿瘤中HMGB1基因的表达及预后价值

目的研究结肠肿瘤中高迁移率族蛋白B1基因（HMGB1）的差异表达及预后价值。 方法从Oncomine及TCGA数据集中筛选出2 191例结肠肿瘤患者HMGB1基因表达数据及临床病理数据,采用Mann-Whitney U检验比较结肠癌与腺瘤、左半结肠癌与右半结肠癌、原位癌与浸润癌、黏液性腺癌与其他病理类型结肠癌、以及发生淋巴结转移与无淋巴结转移、发生远处转移与无远处转移结肠癌组织中HMGB1基因差异表达情况,并绘制Kaplan-Meier生存曲线。 结果HMGB1基因在结肠癌组织和腺瘤组织中均较正常结肠组织高表达（P<0.001）,在结肠癌组织中较结肠腺瘤组织中高表达,在左半结肠癌组织中较右半结肠癌高表达（P<0.05）,在黏液性腺癌组织中较其他病理类型低表达（P<0.05）,在浸润癌组织中较原位癌高表达（P<0.001）。有淋巴结转移及远处转移者较未转移者高表达（P<0.05）。HMGB1基因高表达提示更高的5年生存率（P=0.011）,尤其对于女性结肠癌患者（P=0.006）。 结论HMGB1基因可作为判断结肠癌浸润深度、淋巴转移、远处转移及预后的标志物。     

LOXL2 serves as a prognostic biomarker for hepatocellular carcinoma by mediating immune infiltration and vasculogenic mimicry

BackgroundThe development of human hepatocellular carcinoma (HCC) is a multistep process that is accompanied by progressive changes in the liver microenvironment, including immune evasion and angiogenesis. Lysyl oxidase-like 2 (LOXL2) has been suggested to contribute to tumour progression and metastasis; however, the underlying mechanism remains unclear. The purpose of the present study was to explore the relationship between LOXL2 and immune infiltration and vasculogenic mimicry (VM) and to identify the role of LOXL2 in HCC diagnosis prognosis evaluation.MethodsThe Cancer Genome Atlas (TCGA), UALCAN, GEPIA and Kaplan–Meier plotter databases were used to analyse LOXL2 expression and perform survival analysis. The Tumour Immune Estimation Resource (TIMER) was used to analyse immune cell infiltration, immune cell biomarkers and immune checkpoints. Immunohistochemistry (IHC) of 201 HCC samples was used to confirm the expression of LOXL2 and its relationship with VM. Coimmunoprecipitation (co-IP) and gain- and loss-of-function studies were performed to confirm the molecular mechanism of LOXL2 in VM.ResultsThe expression of LOXL2 in HCC was higher than that in normal tissues at both the mRNA and protein levels. High expression of LOXL2 was associated with a poorer prognosis of HCC. The genetic alteration rate of LOXL2 was 5%. LOXL2 was positively related to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. Co-IP showed that LOXL2 can interact directly with IQGAP1. Both gain- and loss-of-function studies showed that LOXL2 significantly induced cell migration, invasion and VM formation when IQGAP1 was upregulated.ConclusionsLOXL2 is involved in immune cell infiltration and promotes VM by upregulating IQGAP1. LOXL2 can be used as a novel biomarker for HCC diagnosis and prognosis prediction.     

Long non-coding RNA OIP5-AS1 promotes the growth of gastric cancer through the miR-367-3p/HMGA2 axis

Increasing evidence shows that aberrant lncRNAs expression contributes to the progression of gastric cancer (GC). The role of the novel lncRNA OIP5-AS1 and its underlying mechanisms in the growth of GC is largely unknown. Here we demonstrate for the first time that OIP5-AS1 expression was up-regulated in GC tissues and cell lines, which significantly correlated with unfavorable clinical characteristics and shorter survival. The results of in vitro and in vivo gain- and loss-of-function experiments indicate that OIP5-AS1 promoted cell proliferation and colony formation while inhibiting apoptosis of GC cells. OIP5-AS1 functioned as an endogenous sponge for miR-367-3p in GC cells. Restoration of miR-367-3p expression abolished the biological effects of OIP5-AS1 on GC cells. Moreover, we show that HMGA2 was a downstream target of miR-367-3p and mediated the effects of OIP5-AS1 on GC cells. OIP5-AS1 regulated the activities of the PI3K/AKT and Wnt/β-catenin pathways through HMGA2. In conclusion, OIP5-AS1 functions as an oncogenic lncRNA that promotes the progression of GC and may serve as a therapeutic target for managing GC.     

长链非编码RNA EXOC7在非小细胞肺癌中的表达及临床意义分析

目的分析长链非编码RNA(lncRNA)EXOC7在非小细胞肺癌中的表达及临床意义。方法本研究纳入2015年1月~2018年5月收治的75例非小细胞肺癌患者,采用实时定量反转录聚合酶链反应(qRT-PCR)方法检测lncRNA EXOC7在非小细胞肺癌组织及对应癌旁组织中的表达,比较癌及癌旁组织中lncRNA EXOC7的表达差异性,并分析癌组织中lncRNA EXOC7的表达与患者临床病理特征及预后的关系。结果非小细胞肺癌组织中lncRNA EXOC7的相对表达水平(7.88±1.04)明显高于癌旁组织(1.33±0.79),差异具有统计学意义(P<0.001)。不同性别、年龄、病理类型、组织分化程度的非小细胞肺癌患者组织中lncRNA EXOC7的表达无明显差异性(P>0.05),但不同TNM分期、淋巴结转移状况与非小细胞肺癌患者组织中lncRNA EXOC7的表达存在显著差异性(P<0.05)。lncRNA EXOC7高表达组无进展生存期[(10.09±1.93)个月]明显短于低表达组[(19.77±2.16)个月],差异有统计学意义(P<0.05)。lncRNA EXOC7高表达组总生存期[(14.82±2.05)个月]明显短于低表达组[(26.18±2.87)个月],差异有统计学意义(P<0.05)。结论lncRNA EXOC7在非小细胞肺癌组织中表达上调,其可能作为一种促癌因子参与非小细胞肺癌的发生及发展过程,并与患者的不良预后有关。     

Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis

BACKGROUNDPrevious studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIMTo investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODSThe expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTSThe expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSIONOur results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.