Genomic Landscape and Immune Microenvironment Features of Preinvasive and Early Invasive Lung Adenocarcinoma

BackgroundUnderstanding the genomic landscape and immune microenvironment features of preinvasive and early invasive lung adenocarcinoma may provide critical insight and facilitate development of novel strategies for early detection and intervention.MethodsA total of 80 tumor tissue samples and 30 paired histologically normal lung tissue samples from 30 patients with adenocarcinoma in situ (AIS) (n = 8), minimally invasive adenocarcinoma (MIA) (n = 8), and invasive adenocarcinoma (IAC) (n = 14) were subjected to multiregion whole exome sequencing and immunohistochemistry staining for CD8 and programmed death ligand 1 (PD-L1).ResultsAll tumors, including AIS, exhibited evidence of genomic intratumor heterogeneity. Canonical cancer gene mutations in EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), NRAS, and BRAF were exclusively trunk mutations detected in all regions within each tumor, whereas genes associated with cell mobility, gap junction, and metastasis were all subclonal mutations. EGFR mutation represented the most common driver alterations across AIS, MIA, and IAC, whereas tumor protein p53 gene (TP53) was identified in MIA and IAC but not in AIS. There was no difference in PD-L1 expression among AIS, MIA, and IAC, but the CD8 positivity rate was higher in IAC. Tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations.ConclusionsMutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression. Genomic intratumor heterogeneity and immunoediting are common and early phenomena that may have occurred before the acquisition of invasion.     

复方杜仲健骨颗粒治疗膝关节骨性关节炎Ⅱ期临床试验总结

目的：评价复方杜仲健骨颗粒治疗膝关节骨性关节炎的临床疗效和安全性。方法：采用多中心、双盲双模拟随机对照方法，将膝关节骨性关节炎患者200例分为复方杜仲健骨颗粒组（试验组）100例，壮骨关节丸组（对照组）100例，对比分析两组的临床疗效。结果：①试验组总有效率为92％，对照组总有效率为82％，试验组疗效优于对照组（P＜0．01）。②两组治疗单项症状均有效。③试验组治疗中医证候有效，且优于对照组。④试验组在治疗过程中未见明显不良反应。结论：复方杜仲健骨颗粒是一种治疗膝关节炎安全有效的药物。