THE EFFECT OF ACTIVE COMPONENTS OF LYCIUM BARBARUM AND GARLIC (LB-GO) ON THE SYNTHESIS OF DNA AND ULTRASTRUCTURE OF U_(14) CERVIX CANCER CELLS IN MICE

Mice, inoculated with U_(14) ascitic type cervix cancer cells, were administered with effective components of Lycium barbarum (LB) and garlic (GO).On the 4th day after i.p.administration, general condition of the animals were found improved.Examination of ascitic fluid revealed damage of the cancer cells, blanching of fluorescence staining of DNA and RNA, and the cancer cells besieged by large numbers of macrophages and leucocytes. Flow cell metric (FCM) analysis found: accumulation of cells of G_1 stage. Ultrastructure study disclosed: swelling of mitochondria in cytoplasm and damage of mitochondrial crests even with cavity formation, enlargement and degranulation of rough ER. It seemed the effect of LBGO was affirmable. It was postulated that macrophages,being activated by LB, came in close contact with the cancer cells giving rise to carcinolysis. In addition to the direct but transient killing effect of GO, the anti-cancer results could be greatly enhanced.

Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging,invasion,and metastasis

BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.

同源异型盒基因A5、三结构域蛋白14与结直肠癌的关系

目的探讨结直肠癌组织同源异型盒基因A5(HOXA5)、三结构域蛋白14(TRIM14)蛋白表达水平与临床病理特征及患者预后的关系。方法回顾性收集整理2016年5月至2018年5月期间于河南中医药大学郑州人民医院确诊的120例结直肠癌患者癌组织及癌旁组织标本及相关临床资料,采用免疫组化法检测组织HOXA5、TRIM14蛋白表达水平;分析HOXA5、TRIM14水平与结直肠癌患者临床病理特征及预后的关系;采用Kaplan-Meier法分析组织中HOXA5、TRIM14表达与结直肠癌5年生存率的关系;采用Cox比例风险回归模型分析结直肠癌5年预后影响因素。结果结直肠癌组织中TRIM14蛋白阳性率为73.33%,明显高于癌旁组织的10.00%,HOXA5蛋白阳性率为27.50%,明显低于癌旁组织的81.67%,差异均有统计学意义(P<0.05)。TRIM1蛋白阳性表达患者肿瘤低分化比例为42.05%,浸润深度T_(3)~T_(4)比例为72.73%,有淋巴结转移比例为47.73%,有远处转移比例为29.55%,明显高于TRIM1蛋白阴性表达的12.50%、37.50%、12.50%、6.25%,差异均有统计学意义(P<0.05);HOXA5蛋白阴性表达患者肿瘤低分化比例为41.38%,浸润深度T3~T4比例为77.01%,有淋巴结转移比例为48.28%,有远处转移比例为29.89%,明显高于HOXA5蛋白阳性表达的15.15%、27.27%、12.12%、6.06%,差异均有统计学意义(P<0.05)。结直肠癌组织中HOXA5阴性表达和TRIM14阳性表达患者的5年生存率分别为57.47%、59.09%,明显低于HOXA5阳性表达患者的90.91%和TRIM14阴性表达患者的87.50%,差异均有统计学意义(P<0.05)。死亡组患者有淋巴结转移比例为85.00%,有远处转移比例为55.00%,明显高于生存组的15.00%、7.50%,差异均有统计学意义(P<0.05)。经Cox比例风险回归模型分析结果显示,TRIM14是结直肠癌患者5年内死亡的独立危险因素,HOXA5是结直肠癌患者5年内死亡的保护因素(P<0.05)。结论结直肠癌组织中TRIM14呈高表达状态,HOXA5呈低表达状态,两者均与TNM分期、肿瘤分化程度、浸润深度等临床病理特征及预后相关,有作为预后标志物及治疗靶点的潜力。

宫颈癌组织中LRRC8A、METTL14的表达及临床预后价值

目的分析宫颈癌(CC)组织中富含亮氨酸重复蛋白8A(LRRC8A)、甲基转移酶样蛋白14(METTL14)的表达,探讨两者的临床意义。方法回顾性选取2019年2月—2021年3月榆林市第一医院妇产科诊治CC术后患者138例的临床资料和病理组织,采用实时荧光定量PCR和免疫组化法检测CC组织中LRRC8A、METTL14 mRNA及蛋白表达;绘制K-M生存曲线,用Log-Rank检验比较曲线的差异;Cox回归模型筛选CC预后影响因素。结果CC癌组织中LRRC8A、METTL14 mRNA表达量高于癌旁组织(t/P=44.520/<0.001,42.352/<0.001),癌组织LRRC8A、METTL14蛋白阳性率高于癌旁组织(χ^(2)/P=124.062/<0.001,107.574/<0.001);FIGO分期ⅠB2~ⅡA期、淋巴结转移患者癌组织LRRC8A、METTL14蛋白阳性率明显高于ⅠA~ⅠB1期及无淋巴结转移患者(LRRC8A:χ^(2)/P=6.338/0.012、4.886/0.027;METTL14:χ^(2)/P=7.547/0.006、10.294/0.001);LRRC8A阳性和阴性组3年总生存率分别为71.43%(70/98)、90.00%(36/40);METTL14阳性和阴性组3年总生存率分别为70.65%(65/92)、89.13%(41/46)。Log-Rank检验结果显示,LRRC8A阳性组、METTL14阳性组3年总生存率分别低于LRRC8A阴性组、METTL14阴性组(Log-Rankχ^(2)=5.065、7.690,P=0.023、0.006);Cox回归分析结果表明,LRRC8A阳性、METTL14阳性、FIGO分期ⅠB2~ⅡA期是影响CC患者生存预后的独立危险因素[OR(95%CI)=1.679(1.301~2.166),1.429(1.156~1.766),1.713(1.187~2.471)]。结论CC组织中LRRC8A、METTL14表达升高,与CC患者FIGO分期、淋巴结转移有关,是评估CC患者不良生存预后的标志物。

Interaction of 14-3-3σ with KCMF1 suppresses the proliferation and colony formation of human colon cancer stem cells

AIM: To investigate the biological function of 14-3-3σ protein and to look for proteins that interact with 14-3-3σ protein in colon cancer stem cells. METHODS: Reverse transcription polymerase chain reaction was performed to amplify the 14-3-3σ gene from the mRNA of colon cancer stem cells. The gene was then cloned into the pGEM-T vector. After being sequenced, the target gene 14-3-3σ was cut from the pGEM-T vector and cloned into the pGBKT7 yeast expression plasmid. Then, the bait plasmid pGBKT7-14-3-3σ was transformed into the yeast strain AH109. After the expression of the pGBKT7-14-3-3σ fusion protein in the AH109 yeast strain was accomplished, a yeast two-hybrid screening assay was performed by mating AH109 with Y187 that contained a HeLa cDNA library plasmid. The interaction between the 14-3-3σ protein and the proteins obtained from positive colonies was further confirmed by repeating the yeast two-hybridscreen. After extracting and sequencing the plasmids from the positive colonies, we performed a bioinformatics analysis. A coimmunoprecipitation assay was performed to confirm the interaction between 14-3-3σ and the proteins obtained from the positive colonies. Finally, we constructed 14-3-3σ and potassium channel modulatory factor 1 (KCMF1) siRNA expression plasmids and transfected them into colon cancer stem cells. RESULTS: The bait plasmid pGBKT7-14-3-3σ was constructed successfully, and the 14-3-3σ protein had no toxic or autonomous activation effect on the yeast. Nineteen true-positive colonies were selected and sequenced, and their full-length sequences were obtained. We searched for homologous DNA sequences for these sequences from GenBank. Among the positive colonies, four coding genes with known functions were obtained, including KCMF1 , quinone oxidore-ductase (NQO2 ), hydroxyisobutyrate dehydrogenase (HIBADH ) and 14-3-3σ . For the subsequent coimmu-noprecipitation assay, the plasmids PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc-HIBADH were successfully constructed, and the sequences were further confirmed by DNA sequencing. The Fugene 6 reagent was used to transfect the plasmids, and fluorescence-activated cell sorting analysis showed the transfection efficiency was 97.8% after 48 h. The HEK 293FT cells showed the stable expression of the PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc-HIBADH plasmids. After anti-Myc antibody immunoprecipitation with Myc-KCMF1, Myc-NQO2 and Myc-HIBADH from cell lysates, the presence of Flag-14-3-3σ protein in the immuno-precipitated complex was determined by western blot analysis. The knock-down expression of the 14-3-3σ and KCMF1 proteins significantly inhibited cell proliferation and colony formation of SW1116csc. CONCLUSION: Genes of the proteins that interactedwith 14-3-3σ were successfully screened from a HeLa cDNA library. KCMF1 and 14-3-3σ protein may affect the proliferation and colony formation of human colon cancer stem cells.

The role of epigenetic inactivation of 14-3-3σ in human cancer

Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. Thep53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma ofthe breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor progression.Functional studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chro-mosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approachimplies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σexpression in cancer cells.

Clinical implication of 14-3-3 epsilon expression in gastric cancer

AIM:To evaluate for the first time the protein and mRNA expression of 14-3-3εin gastric carcinogenesis.METHODS:14-3-3εprotein expression was determined by western blotting,and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples.RESULTS:Authors observed a significant reduction of 14-3-3εprotein expression in gastric cancer(GC)samples compared to their matched non-neoplastic tissue.Reduced levels of 14-3-3εwere also associated with diffuse-type GC and early-onset of this pathology.Our data suggest that reduced 14-3-3εmay have a role in gastric carcinogenesis process.CONCLUSION:Our results reveal that the reduced 14-3-3εexpression in GC and investigation of 14-3-3ε interaction partners may help to elucidate the carcino-genesis process.

Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans

AIM: To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer.

The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy

Tumor cells have an increased demand for glucose and amino acids to support their rapid growth,and also exhibit alterations in biochemical pathways that metabolize these nutrients.Transport across the plasma membrane is essential to feed glucose and amino acids into these tumor cell-selective metabolic pathways.Transfer of amino acids across biological membranes occurs via a multitude of transporters;tumor cells must upregulate one or more of these transporters to satisfy their increased demand for amino acids.Among the amino acid transporters,SLC6A14 stands out with specific functional features uniquely suited for the biological needs of the tumor cells.This transporter is indeed upregulated in tumors of epithelial origin,including colon cancer,cervical cancer,breast cancer,and pancreatic cancer.Since normal cells express this transporter only at low levels,blockade of this transporter should lead to amino acid starvation selectively in tumor cells,thus having little effect on normal cells.This offers a novel,yet logical,strategy for the treatment of cancers that are associated with upregulation of SLC6A14.In addition,a variety of amino acid-based prodrugs are recognized as substrates by SLC6A14,thus raising the possibility that anticancer drugs can be delivered into tumor cells selectively via this transporter in the form of amino acid prodrugs.This strategy allows exposure of SLC6A14-positive tumor cells to chemotherapy with minimal off-target effects.In conclusion,the amino acid transporter SLC6A14 holds great potential not only as a direct drug target for cancer therapy but also for tumor cell-selective delivery of anticancer drugs.

Prognostic significance of 14v-lymph node dissection to D2 dissection for lower-third gastric cancer

BACKGROUND Radical gastrectomy with D2 lymph node (LN) dissection is the standard surgical procedure for patients with resectable gastric cancer (GC). In the fifteenth edition of the Japanese Classification of Gastric Carcinoma, the 14v LN (LNs along the root of the superior mesenteric vein) was defined as the regional gastric LN. The efficacy of 14v LN dissection during radical distal gastrectomy for lower-third GC remains controversial. AIM To analyze whether the addition of 14v LN dissection improved the survival of patients with lower-third GC. METHODS The data from 65 patients who underwent 14v LN dissection and 65 patients treated without 14v LN dissection were selected using the propensity scorematched method from our institute database constructed between 2000 and 2012. Overall survival was compared between the groups. RESULTS Overall survival was similar between patients with 14v LN metastasis and those with distant metastasis (P = 0.521). Among patients with pathological stage IIIA disease, those who were treated with 14v LN dissection had a significantly higher overall survival than those treated without it (P = 0.020). Multivariate analysis showed that age < 65 years and pT2-3 stage were independent favorable prognostic factors for prolonged overall survival in patients with pathological stage IIIA disease. Patients with No. 1, No. 6, No. 8a, or No. 11p LN metastasis were at higher risk of having 14v LN metastasis.CONCLUSION Adding 14v LN dissection to D2 dissection during radical distal gastrectomy may improve the overall survival of patients with pathological stage IIIA lower-third GC.

Transfer of p14ARF gene in drug-resistant human breast cancer MCF-7/Adr cells inhibits proliferation and reduces doxorubicin resistance

Objective: To elucidate the effect of p14ARF gene on multidrug-resistant tumor cells. Methods: We transferred a p14ARF cDNA into p53-mutated MCF-7/Adr human breast cancer cells. Results: In this report we demonstrated for the first time that p14ARF expression was able to greatly inhibit the MCF-7/Adr cell proliferation. Furthermore, p14ARF expression resulted in decreases in MDR1 mRNA and P-glycoprotein production, which linked with the reducing resistance of MCF-7/Adr cells to doxorubicin. Conclusion: These results imply that drug resistance might be effectively reversed with the wild-type p14ARF expression in human breast cancer cells.

Effect of SNC19/ST14qene overexpression on invasion of colorectal cancer cells

AIM： TO study the effect of SNC19/ST14gene overexpression on invasion in vitro of colorectal cancer cells. METHODS： The adhesion of SlVC19/ST14gene-transfected cells to ECM was measured by MTT assay. The cell movement was evaluated by wound healing assay. Cell invasion and migration were determined by invasion assay in vitro. RESULTS： SNC19/ST14 gene overexpression could enhance invasion of colorectal cancer cells in vitro significantly and influence early cell adherence to ECM, but could not change cell movement significantly. CONCLUSION： SNC19/ST14 gene overexpression increases the local invasion of colorectal cancer cells in vitro. 2005 The WJG Press and Elsevier Inc. All rights reserved.

HYPERMETHYLATION OF p14^(ARF) PROMOTER REGION AND EXPRESION OF p14^(ARF) GENE PRODUCT IN NON-SMALL CELL LUNG CANCER

Objective： This study was designed to investigate promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer, and value the role of p14^ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods： Promoter methylation status and protein expression of p14^ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction （MSP）, restriction enzyme-related polymerase chain reaction （RE-PCR） and immunohistochemistry （IHC）. Results： The positive rates of p14^ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% （7/40） and 2.5% （1/40） respectively. There were statistically significant differences between them, P〈0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14^ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p〈0.01. Promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer showed significantly an inverse correlation （r=-0.56, P〈0.01）, and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion： Promoter methylation is a crucial mechanism of inactivation of p14^ARF gene. Promoter methylation of p14^ARF gene might he involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future.

Circular RNA circFOXM1 triggers the tumorigenesis of non-small cell lung cancer through miR-132-3p/TMEM14A axis

Farlier studies indicated that circular RNAs(circRNAs)were found in various cancer clls,and circFOXM1 was reported to act as an oncogane in non-small cell lung cancer(NSCLC).However,the function of circFOXM1 in NSCLC remains undear.The epression lewels of genes were measured using quantative real-time polymerase chain reactions(qRT-PCR).Cell prolferation and apoptosis were determined by 3-(4,5 dimethylthiazol-2-yl)-25 dipbenyletrazolium bromide solution(MTT)and flow cytometry assay.The rdative protein expression was assed by westen blot Moreower,transwell assays were employed to examine ell migration and invasion.The targeted relationship was confirmed by dual-luciferase reporter assay.The expression of circFOXMI was up-regulated in NSCIC tissues and cell lines.The depletion of circFOXM1 decreased the prolferation,migration,invasion,and induced cell apoptosis of NSCLC cells.MicroRNA-132-3p(MiR-1323p)was idenified as a target of dircFOXMl.The expression level of miR-132-3p was decrased in NSCLC tssues and cell lines and inversely corrdated with circFOXM1 expression.Furthermore,the efects of drdOXMl down regulation on NSCLC cell progression were abolished by mR-1323p inhibitor.Transmembrane protein 14A(TMEM14A)was verifed as a target gene of miR-132-3p.The efects of circFOXM1 depletion on NSCLC cell proliferation,apoptosis,migration,and invasion were reversed by TMEMI4A overexpression.Our study demonstrated that knodkdown of circFOXM1 suppressed NSCLC progression through rqgulating miR-132-3p/TMEMI4A axis,sugesting the drFOXM/miR-132-3p/TMEM14A axis may serve as the novd target for NSCLC diagnosis and therapy.

p73 G4C14 to A4T14 polymorphism is associated with colorectal cancer risk and survival

AIM:To analyze the association between the p73 G4C14-to-A4T14 polymorphism(a.k.a.,the GC/AT variation) and colorectal cancer risk and survival in the Korean population,and to evaluate the relationships between p73 polymorphism and the p73 protein expression or clinicopathological characteristics of colorectal cancer.METHODS:Three hundred and eighty-three histologically confirmed cases and 469 healthy controls,recruited at one teaching hospital in Pusan,Korea from 2001 and 2007,were genotyped for p73 G4C14-to-A4T14 by PCR with confronting two-pair primers(PCR-CTPP) and the expression profile of p73 in cancer tissues(n=383) was analyzed by immunohistochemistry.RESULTS:Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated by unconditional logistic regression model adjusted for age and gender.Compared with the GC/GC genotypes,the GC/AT and AT/AT genotypes were significantly associated with colorectal cancer risk(GC/AT vs GC/GC:OR = 1.46,95% CI:1.10-1.94;AT/AT vs GC/GC:1.72,0.98-3.03;Ptrend=0.01).When stratified by age and gender,the association was restricted to those less than 60 years of age(GC/AT or AT/AT vs GC/GC:2.22,1.39-3.55) and male(GC/AT or AT/AT vs GC/GC:1.91,1.31-2.77).The expression of p73 was associated with invasion depth(P = 0.003) and advanced Duke's stage(P = 0.06) of colorectal cancer.The patients with the GC/GC genotype were associated with worse survival compared with those with the other genotypes(P = 0.02).However,no signif icant relationship was observed between the p73 G4C14-to-A4T14 polymorphism and p73 protein expression in cancer tissues.CONCLUSION:Our results suggest that the p73 GC/AT polymorphism is associated with an increased colorectal cancer risk and survival in the Korean population.

Kruppel样因子14介导的JAK-STAT信号通路对非小细胞肺癌预后的影响

目的探讨Kruppel样因子14(KLF14)介导的Janus激酶-信号转导子与转录激活子(JAKSTAT)信号通路对非小细胞肺癌(NSCLC)预后的影响。方法收集2018年1月至2019年9月本院手术切除的80例NSCLC组织和25例癌旁非肿瘤组织。患者随访至2023年4月结束。采用免疫组织化学检测组织中KLF14表达,根据KLF14表达的中值水平将患者分为高表达组和低表达组。通过在A549细胞中转染KLF14、JAK1过表达质粒和在HCC827细胞中转染KLF14、JAK1特异性短发夹RNA(shKLF14、shJAK1)来过表达或敲低KLF14、JAK1。采用细胞克隆形成试验分析细胞的增殖活力。Transwell分析细胞的迁移、侵袭情况。结果与癌旁正常组织相比,KLF14在NSCLC组织中表达降低(P<0.001)。KLF14的低表达与肿瘤直径>3 cm、淋巴结转移、临床分期Ⅲ期显著相关(P<0.05)。在高KLF14表达组和低KLF14表达组之间的总存活率有显著差异,低KLF14表达的患者预后不良(P<0.05)。KLF14过表达后,A549细胞的增殖能力、迁移和侵袭细胞数均显著降低(P<0.05),而KLF14敲低后,HCC827细胞的增殖能力、迁移和侵袭细胞数均显著增加(P<0.05)。与Vector+KLF14组相比,JAK1+KLF14组A549细胞的集落数、迁移和侵袭数显著增加(P<0.05);而与shNC+shKLF14组相比,shJAK1+shKLF14组HCC827细胞的集落数、迁移和侵袭数显著降低(P<0.05)。结论KLF14低表达与NSCLC患者较差的总生存期相关。KLF14上调显著抑制肺癌细胞在体外的增殖、转移能力,其作用机制可能与抑制JAK-STAT信号通路有关。

CDK14和FOLR1在结肠癌组织中的表达及与患者临床病理特征和预后的关系

目的分析周期蛋白依赖性激酶14(CDK14)、叶酸结合蛋白1(FOLR1)在结肠癌组织中的表达及与患者临床病理特征和预后的关系。方法选择2016年10月至2019年10月由洪湖市人民医院收治的177例结肠癌患者作为研究对象,收集其经手术切除的结肠癌组织及癌旁组织。采用实时荧光定量PCR法检测组织中CDK14、FOLR1的mRNA表达水平。采用免疫组织化学法检测组织中CDK14、FOLR1的蛋白表达情况。采用Pearson法分析结肠癌组织中CDK14、FOLR1表达的相关性。采用Kaplan-Meier生存曲线分析结肠癌组织中CDK14、FOLR1表达与患者预后的关系(采用log-rank检验)。采用COX回归分析探讨结肠癌患者预后的危险因素。结果结肠癌组织中CDK14、FOLR1的mRNA表达水平及其蛋白表达阳性率均显著高于癌旁组织(P均<0.05)。Pearson相关性分析结果显示,结肠癌组织中CDK14与FOLR1表达呈正相关(P<0.05)。结肠癌组织中CDK14、FOLR1表达与患者的TNM分期、分化程度和浸润深度均有相关性(P均<0.05)。Kaplan-Meier生存曲线分析结果显示,结肠癌组织中CDK14、FOLR1阳性表达的患者的3年累积生存率分别显著低于CDK14和FOLR1阴性表达的患者(P均<0.05)。COX回归分析结果显示,结肠癌组织中CDK14、FOLR1阳性表达均是结肠癌患者预后的危险因素(P均<0.05)。结论CDK14、FOLR1在结肠癌组织中表达水平均显著升高,并且两者与患者的TNM分期、分化程度、浸润深度和预后均密切相关,CDK14、FOLR1阳性表达均是结肠癌患者预后的危险因素。

宫颈癌组织IGHG1、TRIM14表达及其临床意义

目的探究宫颈癌组织免疫球蛋白G1重链恒定区(IGHG1)、三结构域蛋白14(TRIM14)的表达及其临床意义。方法收集2019年3月至2020年3月于保定市妇幼保健院收治的82例宫颈癌患者作为研究对象,术中取其肿瘤组织及癌旁组织,并根据3年随访情况分为预后良好组与预后不良组。采用免疫组化法检测宫颈癌肿瘤组织与癌旁组织中IGHG1和TRIM14的蛋白表达水平。采用多因素Logistic回归分析影响宫颈癌患者预后的因素,受试者特征工作(ROC)曲线用于分析宫颈癌患者肿瘤组织中IGHG1和TRIM14蛋白表达水平对预后的预测价值。结果与癌旁组织相比,宫颈癌肿瘤组织中IGHG1和TRIM14蛋白表达水平显著升高(t值分别为34.193、38.697,P<0.05)。IGHG1和TRIM14蛋白表达水平与患者TNM分期、肿瘤分化程度、淋巴结转移有关(t值介于2.092~20.208之间,P<0.05)。与预后良好组相比,预后不良组宫颈癌患者的肿瘤组织中IGHG1和TRIM14蛋白表达水平显著升高(t值分别为8.708、7.534,P<0.05)。多因素Logistic回归分析显示,IGHG1、TRIM14蛋白表达是宫颈癌患者发生不良预后的危险因素,其OR值及95%CI分别为3.547(2.364~5.322)、7.218(2.027~25.704)。ROC分析显示IGHG1、TRIM14联合预测宫颈癌患者预后的曲线下面积为0.957,灵敏度和特异度分别为78.00%和98.25%。结论宫颈癌患者肿瘤组织中IGHG1和TRIM14蛋白水平高表达,与预后有关,可能是宫颈癌预后评估的生物标志物。

MFG-E8和GNA14在子宫内膜异位症相关性卵巢癌中的表达及其临床意义

目的探讨乳脂球表皮生长因子8(MFG-E8)和G蛋白亚基α-14(GNA14)在子宫内膜异位症相关性卵巢癌(EAOC)中的表达及其临床意义。方法选取2015年5月—2017年5月华北医疗健康集团峰峰总医院EAOC患者51例(EAOC组)、非典型子宫内膜异位症(AEM)患者63例(AEM组)、卵巢型子宫内膜异位症(EMT)患者82例(EMT组)。收集所有患者的临床资料,并检测病变组织中MFG-E8、GNA14表达。对EAOC患者随访5年。采用Kaplan-Meier生存曲线分析EAOC患者的生存情况。采用多因素Cox回归分析评估EAOC患者死亡的危险因素。结果EAOC组MFG-E8阳性率为82.35%、GNA14阳性率为70.59%,均显著高于AEM组(41.27%、44.44%)和EMT组(25.61%、23.17%)(P<0.001)。MFG-E8高表达组和低表达组肿瘤直径、肿瘤级别、国际妇产科联合会(FIGO)分期、淋巴转移情况差异均有统计学意义(P<0.05)。GNA14高表达组和低表达组淋巴转移情况差异有统计学意义(P=0.009)。Kaplan-Meier生存曲线分析结果显示,MFG-E8高表达组和GNA14高表达组无进展生存期分别短于MFG-E8低表达组和GNA14低表达组(P<0.05)。多因素Cox回归分析结果显示,FIGO分期Ⅱ期、淋巴转移、MFG-E8高表达、GNA14高表达是EAOC患者死亡的独立危险因素[风险比(HR)值分别为2.337、2.519、3.133、3.080,95%可信区间(CI)分别为1.258~4.342、1.332~4.764、1.381~7.108、1.318~7.197,P<0.01]。结论MFG-E8、GNA14在EAOC患者癌组织中呈高表达,且与患者预后不良密切相关,或可作为EAOC患者的预后评估指标。

SOX14对膀胱癌细胞生物学行为的影响

目的观察性别决定区Y框基因转录因子(SOX)14在膀胱癌组织中的表达情况,探讨其对膀胱癌细胞增殖、迁移和侵袭等生物学行为的影响。方法收集2019年12月至2022年6月温州医科大学附属第一医院手术切除的膀胱癌组织(37例)和癌旁组织(14例),采用qRT-PCR法检测癌组织和癌旁组织中、膀胱癌细胞和正常尿路上皮细胞中SOX14 mRNA的表达水平。使用过表达和敲低SOX14载体转染膀胱癌细胞,采用细胞计数试剂盒(CCK)-8法、细胞划痕实验和Transwell实验检测并比较不同转染细胞增殖、迁移和侵袭能力的差异。结果膀胱癌组织中SOX14 mRNA相对表达量显著低于癌旁组织,5637、T24、EJ、J82和RT4等5种膀胱癌细胞中SOX14 mRNA相对表达量均显著低于正常尿路上皮细胞。相比相应对照组,过表达SOX14后膀胱癌细胞存活率、细胞迁移和侵袭能力均显著降低;敲低SOX14后膀胱癌细胞存活率、细胞迁移和侵袭能力均显著升高。结论SOX14在人膀胱癌组织和细胞中低表达。调控SOX14 mRNA的表达水平能影响膀胱癌细胞的增殖、迁移和侵袭能力。提示SOX14可能是治疗膀胱癌的新靶点。