p16、Ki67及FRα预测低度宫颈上皮内瘤变转归的研究进展

宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)已发现与宫颈癌密切相关,根据异常程度分3级CIN(CIN1,CIN2和CIN3)。约60%的CIN1可自然消退,仅有少部分发生进展。目前,迫切需要一些生物标志物作为预测因子来预测病变的转归。经检索国内外文献发现,目前大部分研究结果发现生物标志物p16、Ki67的染色结果对于CIN1的预后有预测意义,并且有部分学者研究了p16/Ki67双染结果也可以很好的预测,而目前仅少数人研究了FRα在预测CIN1转归时的意义,认为FRα可能有一定预测价值。关于这些生物标志物的预测价值,还需要其他大型的、长时间的临床随访来进一步研究它们的准确性和可靠性,也需要进行更加深入的研究去发现其他更为精准的标志物。     

Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer

Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment (P < 0.01). We used the 10 most differentially‐methylated genes between responders and non–responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes (ROBO1, ULK4P3, MYOD1, LBX1, CACNA1A, IRX4, DPYSL3 and ELAVL2) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression‐free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.     

肺癌诊断相关miRNA标志物的筛选和验证

目的 获得肺癌组织和正常肺部组织中差异表达的miRNA用于肺癌的早期诊断.方法 首先运用miRNA芯片比较5对来自临床的正常肺部组织和肺癌组织,筛选差异性表达的miRNA,然后用荧光实时定量PCR进行鉴定.最后用ROC曲线分析评价特定miRNA标志物区分肺癌组织与正常肺部组织的能力.结果 miR-10b-5p和miR-199a-5p在肺癌组织中的相对表达量(2.76±0.71;2.05±0.38)显著高于肺部正常组织中的相对表达量(1.00±0.17;0.96±0.18),差异有统计学意义(t=2.40、2.56,P＜0.05).ROC曲线评价miR-10b-5p和miR-199a-5p区分肺癌组织和肺部正常组织的能力,曲线下面积(AUC)分别为0.731和0.672.两个miRNA联合区分肺癌组织和肺部正常组织的AUC为0.773,灵敏度为57.9％,特异性为94.7％.结论 miR-10b-5p和miR-199a-5p联合可作为候选肿瘤标志物组合用于早期肺癌诊断.     

Serum YKL‐40 and gestational diabetes – an observational cohort study

To examine serum YKL‐40 in women developing gestational diabetes mellitus (GDM). In the present large observational cohort study of 1179 pregnant women, we determined serum YKL‐40 four times during pregnancy (at gestational age 12, 20, 25, and 32 weeks). Pregnancy outcome was obtained from medical records. Sixty‐eight women (5.8%) developed GDM. Serum YKL‐40 increased from gestational age (GA) 12 weeks and the following weeks in the women who developed GDM and was independent of BMI, parity, and maternal age (OR = 2.69, 95% CI: 1.45–5.00, p = 0.002). No association was found between serum YKL‐40 and the oral glucose tolerance test results. In conclusion, YKL‐40 significantly increased in pregnant women with GDM compared with women without GDM, probably reflecting the low‐grade inflammation of GDM. However, we did not find an association between serum concentrations of YKL‐40 in early pregnancy and the development of GDM and thus we conclude that YKL‐40 alone is not usable as a biomarker for early prediction of GDM.