Objective:To investigate the application value of peripheral blood circulating tumor cell (CTC) classification in the prediction of preoperative microvascular invasion of hepato-cellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinico-pathological data of 102 HCC patients who were admitted to Zhengzhou University People's Hospital from September 2018 to September 2020 were collected. There were 71 males and 31 females, aged from 29 to 80 years, with a median age of 57 years. Observation indicators: (1) surgical situations; (2) results of CTC detection and microvascular invasion in HCC patients; (3) results of CTC classification and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC; (4) influencing factors for microvascular invasion in HCC; (5) comparison of clinicopathological features in HCC patients with different cell counts in mesenchymal phenotype of CTC (M-CTC). Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the nonparametric rank sum U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The receiver operating characteristic (ROC) curve was used to determine the best cut-off value for the risk of microvascular invasion in patients. Univariate and multivariate analysis were performed using the Logistic regression model. Results:(1) Surgical situations. All 102 patients underwent surgery successfully, including 17 cases undergoing local hepatectomy, 43 cases under-going segmentectomy, 22 cases undergoing hepatic lobectomy, 13 cases undergoing hemilectomy and 7 cases undergoing enlarged hemilectomy. The operation time and the volume of intraoperative blood loss were 235(147,293)minutes and 300(110,500)mL of the 102 patients, respectively. (2) Results of CTC detection and microvascular invasion in HCC patients. Of 102 patients, there were 36 casas with epithelial phenotype of CTC (E-CTC), 86 cases with hybrid phenotype of CTC (H-CTC), 30 cases with M-CTC, respectively, and the total CTC (T-CTC) were positive in 89 cases. Results of postoperative pathological examination showed that there were 40 cases with micro-vascular inva-sion and 62 cases without microvascular invasion in the 102 patients. Of the 40 patients with micro-vascular invasion, the count of E-CTC, H-CTC, M-CTC and T-CTC were 0(0,1) per 5 mL, 4(2,5) per 5 mL, 1(0,2) per 5 mL and 5(3,8) per 5mL, respectively. The above indicators of the 62 cases without microvascular invasion were 0(0,1) per 5 mL, 3(1,5) per 5 mL, 0(0,0) per 5 mL and 3(2,6) per 5 mL, respectively. There were significant differences in the count of M-CTC and T-CTC between patients with and without microvascular invasion ( Z=-4.83, -2.96, P<0.05). (3) Results of CTC classi-fication and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC. The ROC curve showed that best cut-off value of M-CTC and T-CTC counts in the prediction of microvascular invasion in HCC were 1 per 5 mL and 4 per 5 mL, respectively, with the area under curve, the corresponding specificity, sensitivity were 0.70 (95% confidence interval as 0.60-0.81, P<0.05), 75.8%, 62.9% and 0.67 (95% confidence interval as 0.57-0.78, P<0.05), 60.0%, 72.5%, respec-tively. (4) Influencing factors for microvascular invasion in HCC. Result of univariate analysis showed that alpha fetoprotein (AFP), aspartate aminotransferase (AST), tumor diameter, tumor number, tumor margin, Barcelona clinic liver cancer staging, M-CTC counts and T-CTC counts were related factors influencing microvascular invasion in HCC ( odds ratio=3.13, 0.43, 4.92, 5.65, 2.54, 2.93, 8.25, 4.47, 95% confidence interval as 1.34-7.33, 0.19-0.98, 2.09-11.58, 2.35-13.63, 1.13-5.75, 1.27-6.74, 3.13-21.75, 1.88-10.61, P<0.05). Result of multivariate analysis showed that tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL were independent risk factors influencing microvascular invasion in HCC ( odds ratio=2.97, 4.14, 4.36, 95% c onfidence interval as 1.01-8.70, 1.14-15.02, 1.36-13.97, P<0.05). (5) Comparison of clinicopathological features in HCC patients with different cell counts in M-CTC. The 102 HCC patients were divided into the high M-CTC group of 30 cases with M-CTC counts ≥1 per 5 mL and the low M-CTC group of 72 cases with M-CTC counts <1 per 5 mL, according to the best cut-off value of M-CTC counts. Cases with hepatitis, cases with AFP >400 μg/L, cases with AST >35 U/L, cases with irregular tumor margin, cases with tumor diameter >5 cm, cases with tumor number as multiple and cases with micro-vascular invasion were 22, 17, 13, 21, 18, 16 and 22 in the high M-CTC group of 30 cases. The above indicators were 35, 18, 48, 26, 25, 21 and 18 in the low M-CTC group of 72 cases. There were significant differences in the above indicators between the high M-CTC group and the low M-CTC group ( χ2=5.25, 9.42, 4.80, 9.79, 5.55, 5.35, 20.75, P<0.05). Conclusions:The epithelial-mesen-chymal phenotype of peripheral blood CTC can be used to predict the preoperative microvascular invasion in HCC. Tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL are independent risk factors influencing microvascular invasion in HCC patients.

目的:研究非小细胞肺癌(NSCLC)患者病灶及癌旁组织胶质瘤相关癌基因同源蛋白-1(Gli-1)、叉头框蛋白C2(FOXC2)表达水平与病理学参数的关联性.方法:选取2019-03～2020-03郑州大学附属郑州中心医院NSCLC患者116例,均检测NSCLC及癌旁组织中Gli-1、FOXC2表达情况并统计相关病理学参数.比较病灶组织、癌旁组织中Gli-1、FOXC2表达水平,并对比不同病理学参数病灶组织中Gli-1、FOXC2的阳性表达率,分析病灶组织中Gli-1、FOXC2表达与相关病理学参数相关性.结果:病灶组织FOXC2表达阳性率71.55％、Gli-1表达阳性率90.52％高于癌旁组织17.24％、12.93％(P＜0.05);病灶组织中Gli-1、FOXC2表达与性别、年龄、组织学类型无关,FOXC2表达与分化程度无关(P＞0.05);临床分期Ⅱ～Ⅲ期、有淋巴结转移患者病灶组织中Gli-1、FOXC2阳性表达率较高,且中低分化程度Gli-1阳性表达率较高(P＜0.05);经Spearman相关性分析,Gli-1表达与分化程度呈负相关,Gli-1、FOXC2表达与临床分期、淋巴结转移呈正相关(P＜0.05)结论:NSCLC患者病灶组织中Gli-1、FOXC2表达水平明显上调,且与淋巴结转移、临床分期等病理学参数具有关联性,有助于病情判断及预后评估.

目的 观察上尿路尿路上皮癌(upper tract urothelial carcinoma,UTUC)患者尿液尿路上皮肿瘤常见突变基因突变情况,探讨尿液基因检测对UTUC早期诊断的价值.方法 拟诊UTUC患者116例均行手术治疗,术前行尿脱落细胞学、荧光原位杂交检测,行尿液基因检测观察尿路上皮肿瘤常见突变基因突变及甲基化情况.以术后组织病理检查结果为金标准,比较尿脱落细胞学、荧光原位杂交、尿液基因检测诊断UTUC的灵敏度、特异度和准确率;绘制ROC曲线,评估尿脱落细胞学、荧光原位杂交、尿液基因检测术前诊断UTUC的效能.结果 基因测序结果显示,116例患者检出TP53基因突变32例,TERT基因突变44例,AKTI基因突变1例,ERBB2基因突变4例,ERCC2基因突变1例,FBXW7基因突变1例,FGFR3基因突变5例,HRAS基因突变10例,KRAS基因突变2例,PIK3CA基因突变10例,RHOA基因突变2例,SF3B1基因突变1例,U2AF1 基因突变2例,ONECUT2 CpG位点甲基化62例.术后组织病理检查结果显示,UTUC 80例,非UTUC 36例.术前尿液基因检测诊断UTUC的灵敏度(92.50％)、准确率(93.10％)均高于尿脱落细胞学(37.50％、52.59％)、荧光原位杂交(45.00％,58.62％)(P＜0.05),特异度(94.44％)与尿脱落细胞学(86.11％)、荧光原位杂交(88.89％)比较差异均无统计学意义(P＞0.05).术前尿脱落细胞学、荧光原位杂交、尿液基因检测诊断 UTUC 的 AUC分别为0.618(95％CI:0.523～0.707,P=0.002)、0.673(95％CI:0.576～0.754,P＜0.001)、0.935(95％CI:0.873～0.972,P＜0.001),术前尿液基因检测诊断UTUC的AUC大于尿脱落细胞学、荧光原位杂交检测(Z=6.749,P＜0.001;Z=5.767,P＜0.001).结论 尿液基因检测尿路上皮肿瘤常见突变基因突变及甲基化情况对UTUC的诊断价值较高.

目的 环状RNA(circRNA)hsa_circ_0024707尚未被报道研究.本研究通过检测hsa_circ_0024707在乳腺癌组织和细胞株中的表达,探索环状RNA hsa_circ_0024707通过调节miR-448对乳腺癌细胞增殖和侵袭的影响.方法 实时定量聚合酶链反应(qPCR)检测乳腺癌组织和细胞株中hsa_circ_0024707的表达.以hsa_circ_0024707表达最低的乳腺癌细胞株感染空载慢病毒(对照组)和载有hsa_circ_0024707的慢病毒(实验组).CCK-8实验和Transwell侵袭实验检测hsa_circ_0024707过表达对乳腺癌细胞株增殖和侵袭的影响.生物信息学技术预测hsa_circ_0024707的下游基因.qPCR和蛋白免疫印迹(Western blot)法检测下游基因的表达.结果 hsa_circ_0024707在乳腺癌组织和癌旁组织中表达分别为1.73±0.46和4.53±0.76(P<0.05).与永生化乳腺上皮细胞比较,hsa_circ_0024707在乳腺癌细胞株中呈低表达(P<0.05),在BT549细胞中的表达量最低(P<0.01).与对照组比较,过表达hsa_circ_0024707可抑制BT549细胞的增殖(P<0.05).对照组和实验组侵袭细胞数分别为82.46±8.49和38.34±8.84(P<0.05).hsa_circ_0024707靶基因可能为miR-448,miR-448靶基因可能为SPRY2.与对照组比较,hsa_circ_0024707过表达导致BT549细胞中miR-448的表达下调(P<0.01),SPRY2的表达上调(P<0.01),Wnt/β-catenin信号通路被抑制.结论 hsa_circ_0024707在乳腺癌组织和细胞株中均呈低表达,hsa_circ_0024707能抑制乳腺癌BT549细胞的增殖和侵袭,其分子机制可能是下调miR-448的表达,上调SPRY2蛋白的表达,抑制Wnt/β-catenin信号通路的活化.