Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis
Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis
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DOI：
10.1016/j.lungcan.2016.11.013
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发表时间：
2017-01-01
期刊：
影响因子：
5.3
通讯作者：
Ishikawa, Yuichi
中科院分区：
文献类型：
--
作者：
Inamura, Kentaro;Yokouchi, Yusuke;Ishikawa, Yuichi
目的：与不吸烟的肺癌相比，吸烟相关的肺癌具有更高的突变负荷，导致产生更多的肿瘤新抗原和增加的免疫原性。B7-H3（也称为CD 276）属于免疫调节剂家族，包括PD-1和PD-L1（也称为B7-H1或CD 274）。考虑到PD-L1抑制剂对吸烟者肺癌更有效的证据，我们在此研究了肿瘤B7-H3表达水平与肺腺癌患者吸烟史的预后相互作用。材料和方法：使用包括270例连续肺腺癌的组织微阵列，我们通过免疫组化评估肿瘤B7-H3表达。我们使用考克斯比例风险回归分析和对数秩检验来检验B7-H3表达水平和吸烟史之间的预后相关性。此外，我们还采用Logistic回归分析来研究B7-H3表达水平与肺腺癌临床病理/分子特征之间的相关性。结果：B7-H3表达与生存的关系因吸烟史而异（P-交互作用= 0.014）; B7-H3高表达与中/重度吸烟患者肺癌特异性生存率降低相关（吸烟指数[SI] >= 400）（风险比[HR] = 3.07，95%置信区间[CI] = 1.74-5.49，P=0.0001;对数秩：P
Objectives: Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients.Materials and methods: Using tissue microarrays comprising 270 consecutive cases of lung adenocarcinoma, we evaluated tumor B7-H3 expression by immunohistochemistry. We examined the prognostic association between B7-H3 expression levels and smoking history, using Cox proportional hazards regression analysis and the log-rank test. Additionally, we used logistic regression analysis to examine the correlations between B7-H3 expression levels and clinicopathological/molecular features of lung adenocarcinoma.Results: The association of B7-H3 expression with survival differed by smoking history (P-interaction = 0.014); high B7-H3 expression was associated with decreased lung cancer-specific survival in moderate/heavysmoking patients (smoking index [SI] >= 400) (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.74-5.49, P=0.0001; log-rank: P