Serum Biomarker Panel for Rapid Early Diagnosis of Lung Cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in most countries. Although early diagnosis and treatment critically influence prognosis, lung cancers are generally only discovered in the late stages of the disease. OBJECTIVE: Widely-used screening and diagnostic methods are not suitable for preventive screening, and high-throughput technologies based on serum biomarkers are needed. METHODS: We screened 501 serum samples, including 224 lung cancer (LC), 126 disease control (DC), and 151 healthy donor (HC) samples for new serum autoantibodies as biomarkers in the early diagnosis of lung cancer. In phase I, we used HuProtTM microarrays to perform preliminary serum antibody screening on 24 LC and 24 HC samples. In phase II, we screened 60 LC, 60 DC, and 60 HC serum samples using focused arrays constructed with 22 of the candidate autoantibody biomarkers screened out in phase I. RESULTS: After data modeling and validation, we selected four potential early LC protein biomarker candidates, IL2RB, CENPB, TP53, and XAGE1A, with individual specificities >90% and sensitivities ranging from 21.2% to 32.2%. These four biomarkers had a specificity of >90% and a sensitivity of >65.5% for early LC when they combined in a panel. Further evaluation of these four biomarker candidates using ELISA assays and 273 serum samples (140 LC, 66 DC, and 67 HC) gave similar results (specificity of >91.7%, sensitivity >61.43%). CONCLUSION: IL2RB, CENPB, TP53, and XAGE1A combined biomarker panel holds potential for rapid screening and improving the diagnosis of early-stage LC, thus potentially also improving its prognosis.

Expression of lncRNA LOC440173 in non-small cell lung cancer tissues and its influence on the maligant biological behaviors of cancer cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：检测lncRNA LOC440173在NSCLC组织和细胞中的表达及探讨其对癌细胞恶性生物学行为的影响。方法：选取河北医科大学第四医院生物标本库中2014至2017年手术切除的72例NSCLC患者的癌及癌旁组织标本，应用qPCR法检测NSCLC组织和癌旁组织中，以及6种NSCLC细胞株（H520、H358、A549、HCC827、H1703和H1299）中LOC440173的表达水平；构建LOC440173的敲低及过表达载体，分别转染H520和H1703细胞，应用MTS、克隆形成及Transwell小室迁移和侵袭实验分别检测敲低及过表达LOC440173对NSCLC细胞增殖、迁移及侵袭能力的影响，qPCR法检测LOC440173对于EMT过程相关标志物（E-cadherin、N-cadherin及vimentin）mRNA表达水平的影响，WB法检测其对E-cadherin、N-cadherin蛋白表达的影响。结果：LOC440173在NSCLC组织中的表达明显高于癌旁组织（P<0.01），并与淋巴结转移、组织学分化程度、TNM分期和肿瘤大小有关联（P<0.05或P<0.01）。敲低LOC440173可以抑制H520细胞的体外增殖、迁移和侵袭（P<0.05或P<0.01），过表达LOC440173可显著促进H1703细胞的增殖、迁移和侵袭（P<0.05或P<0.01）。在转录水平上，敲低LOC440173后，E-cadherin的表达水平升高，间充质相关标志物N-cadherin、vimentin的表达水平降低（P<0.05或P<0.01）；而过表达LOC440173后，E-cadherin的表达水平降低，间充质相关标志物N-cadherin、vimentin的表达水平升高（P<0.05或P<0.01）。在转录后水平上，LOC440173负向调节E-cadherin蛋白的表达、正向调节N-cadherin的蛋白表达（均P<0.05）。结论：LOC440173在NSCLC组织中的异常高表达可能与NSCLC的发生发展有关，LOC440173可显著提高NCSCL细胞的体外增殖、迁移、侵袭能力，且其作用机制可能与调控EMT相关基因表达有关。