The correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma patients: a single center case series

Objective:To investigate the correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma(LADC)patients.Methods:We reviewed 428 consecutive,surgically resected cases of LADC from October 2015 to December 2016 from our center.PD-L1 expression was evaluated based on tumor proportion score(TPS).Correlation and co-occurrence of PD-L1 expression level with those of classical driver genes,such as EGFR,ALK,ROS-1,and KRAS and with clinical variables and disease-free survival(DFS)were analyzed.Results:Seventy of the 428 cases(16.4%)showed TPS≥1%,and 21 cases(4.9%)showed TPS≥50%.PD-L1 positive expression was significantly associated with male gender,smoking,advanced TNM stage,and solid histologic subtype.Both TPS≥1% and ≥50%were correlated with the absence of an EGFR mutation(P<0.001)and the presence of ALK rearrangement(P=0.024).KRAS mutation was associated with TPS≥50%(P=0.035).PD-L1 positivity commonly overlapped with the alterations of classical driver oncogenes(58.5%with TPS≥1% and 42.9% with TPS≥50%).Approximately three-quarters of PD-L1 positive cases co-occurred with classical therapeutic-gene aberrations in cases with stage III/IV cancer or cancer progression.LADC could be divided into four subgroups based on the expression profile of current routine biomarkers for potential therapeutic strategies.Conclusions:PD-L1 expression is not only closely correlated with classic gene alterations but also commonly overlaps with the aberrations of classical driver oncogenes in Chinese LADC patients.These findings provide a useful overview of clinical strategies that rely on the profile of routinely used molecular biomarkers.

Smac调控Caspase-3对耐药肺腺癌细胞株生物活性及相关信号的研究

目的:探讨Smac基因调控Caspase-3表达对紫杉醇耐药肺腺癌细胞株生物活性及经典凋亡信号通路的作用机制。方法:取构建好的耐药A549细胞,将其分为A549细胞(LC)组、A549细胞+Smac-NC(SN)组、A549细胞+Smac抑制剂(SI)组、A549细胞+Smac激动剂(SM)组、A549细胞+Caspase-3-NC(CN)组、A549细胞+Caspase-3抑制剂(CI)组、A549细胞+Caspase-3激动剂(CM)组、A549细胞+Smac激动剂+Caspase-3激动剂(MM)组;Real-time PCR法检测正常肺上皮细胞及4种肺腺癌细胞系中Smac、Caspase-3表达水平,将阴性对照、Smac、Caspase-3类似物转染至紫杉醇耐药肺腺癌细胞株,MTT法检测细胞增殖,流式细胞仪检测细胞凋亡,免疫印迹法检测经典凋亡信号通路表达,并分析Smac与Caspase-3的相关性。结果:肺腺癌细胞系中的Smac、Caspase-3 m RNA表达量显著低于正常肺上皮细胞系BEAS-2B (P<0.05),其中A549的Smac、Caspase-3 m RNA值最小(P<0.05),因此选取其作为此次实验细胞;LC组与SN组相比,细胞增殖率、凋亡率及Caspase-3、Bcl-2、Bax、Cyto-C蛋白表达基本无差异(P>0.05),与SN组相比,SI组细胞凋亡率及Caspase-3、Bax、Cyto-C蛋白表达明显降低(P<0.05),增殖率、Bcl-2表达明显升高(P<0.05),与SI组相比,SM组细胞凋亡率及Caspase-3、Bax、Cyto-C蛋白表达明显升高(P<0.05),增殖率、Bcl-2表达明显降低(P<0.05);LC组与CN组相比,细胞增殖率、凋亡率及Caspase-3、Bcl-2、Bax、Cyto-C蛋白表达基本无差异(P>0.05),与CN组相比,CI组细胞凋亡率及Caspase-3、Bax、Cyto-C蛋白表达明显降低(P<0.05),增殖率、Bcl-2表达明显升高(P<0.05),与CI组相比,CM组细胞凋亡率及Caspase-3、Bax、Cyto-C蛋白表达明显升高(P<0.05),增殖率、Bcl-2表达明显降低(P<0.05);SM组与CM组相比,细胞增殖率、凋亡率及Caspase-3、Bcl-2、Bax、Cyto-C蛋白表达基本无差异(P>0.05),与CM组相比,MM组细胞凋亡率及Caspase-3、Bax、Cyto-C蛋白表达明显升高(P<0.05),增殖率、Bcl-2表达明显降低(P<0.05);Smac与Caspase-3呈现正相关(r=0.470,P=0.002),组间具有显著差异。结论:Smac基因可显著改善紫杉醇耐药肺腺癌细胞株细胞生物活性,并激活经典凋亡信号通路,其作用机制可能与调控Caspase-3表达有关。

cMRI联合纹理分析评估直肠黏液腺癌的价值

目的探讨基于MRI T2WI及增强序列的纹理分析在鉴别直肠经典型腺癌、部分黏液腺癌及黏液腺癌中的价值。方法回顾性分析41例经手术病理证实的直肠腺癌患者临床及影像资料,依据病理将其分为直肠经典型腺癌组22例、部分黏液腺癌组11例和黏液腺癌组8例。使用ITK-SNAP软件在横轴位T2WI和动态增强序列上以肿瘤实性成分最大层面为中心,连续三层进行ROI手动勾画。将勾画好的ROI文件导入美国GE公司AK软件内,利用不同的纹理参数进行特征提取,从而得到肿瘤内部的纹理特征值。选取熵、偏度、峰度等纹理参数作为分析指标。采用SPSS软件中的单因素方差分析、LSD-t及Kruskal-Wallis检验对3组数据间进行两两比较,分析3组之间纹理参数差异是否有统计学意义。结果增强序列中的纹理参数熵、偏度、峰度、均匀度、均值及T2WI序列中的纹理参数平均值、偏度和峰度3组数据之间的两两比较中差异无统计学意义(P>0.05);T2WI序列中的纹理参数熵、均匀度和标准差在鉴别经典型腺癌组、部分黏液腺癌组及黏液腺癌组的两两比较中差异均有统计学意义(P<0.05)。结论cMRI联合纹理分析在鉴别直肠经典型腺癌、直肠黏液腺癌和部分黏液腺癌中存在一定的价值,其中纹理分析在鉴别直肠经典型腺癌和部分黏液腺癌中具有较大的临床意义。