B7-H4 and HHLA2, members of B7 family, are aberrantly expressed in EGFR mutated lung adenocarcinoma
B7-H4 and HHLA2, members of B7 family, are aberrantly expressed in EGFR mutated lung adenocarcinoma
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B7家族成员B7-H4和HHLA2在EGFR突变肺腺癌中异常表达
DOI：
10.1016/j.prp.2020.153134
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发表时间：
2020-10-01
影响因子：
2.8
通讯作者：
Yu, Shaorong
中科院分区：
文献类型：
--
作者：
Chen, Yan;Hu, Ran;Yu, Shaorong
背景：为了寻找不同EGFR突变状态肺癌的新免疫靶点，我们描述了新发现的B7家族成员检查点分子的差异表达谱，以寻找不同EGFR突变状态肺癌的新免疫靶点。方法：我们用B7-H3、B7-H4、VISTA、B7-H6、HHLA2、IDO-1、 肺腺癌组织中的 PD-L1 和 CD8 由发现队列中的 372 例病例和验证集中的 231 例病例构建。描述并比较了这些指标在 EGFR 突变型和野生型肺腺癌中的差异表达谱。 结果：在发现队列中，EGFR 突变型组的 B7-H4 和 HHLA2 中位 IHC 评分显着高于野生型组（中位评分[四分位数范围]，突变型与野生型：3.250 [0-7.000] 与 5.000 [1.000-7.000] 相比，B7-H4 的 P = 0.045； HHLA2 为 8.000 [6.000-10.500] 与 7.000 [5.000-8.630] P = 0.003）。同时，野生型组IDO-1和PD-L1的中位IHC评分显着高于突变型组（中位评分[四分位数范围]，突变型与野生型：1.000 [0-5.000] vs. 3.000 [0-8.500]，IDO-1 P = 0.000；0 [0-3.500] vs. 3.000 [0-6.000]，P = 0.000 PD-L1）。上述结果在发现队列中得到了证实。 CD8表达水平升高和HHLA2表达水平降低与肺腺癌的长期无病生存相关（CD8表达P = 0.000，HHLA2表达P = 0.004）。结论：B7-H4和HHLA2是肺腺癌有希望的免疫靶点，特别是对于EGFR突变患者。
Background: In order to find new immune targets for lung cancer with different EGFR mutant status, we describe differential expression profiles of checkpoint molecules of the new discovery B7 family member to find new immune targets for lung cancer with different EGFR statuses.Methods: We performed immunohistochemistry with antibodies of B7-H3, B7-H4, VISTA, B7-H6, HHLA2, IDO-1, PD-L1 and CD8 in lung adenocarcinoma tissues constructed from 372 cases in the discovery cohort and 231 cases in the validation set. The differential expression profiles of these indices in EGFR mutant and wild-type lung adenocarcinoma was described and compared.Results: In the discovery cohort, the median IHC scores of B7-H4 and HHLA2 for the EGFR mutant group were significantly higher than those in the wild-type group (median score [interquartile range], mutant vs. wild type: 3.250 [0-7.000] vs. 5.000 [1.000-7.000], P = 0.045 for B7-H4; 8.000 [6.000-10.500] vs. 7.000 [5.000-8.630] P = 0.003 for HHLA2). Meanwhile, the median IHC scores of IDO-1 and PD-L1 in the wild-type group were significantly higher than those in the mutant group (median score [interquartile range], mutant vs. wild type: 1.000 [0-5.000] vs. 3.000 [0-8.500], P = 0.000 for IDO-1; 0 [0-3.500] vs. 3.000 [0-6.000], P = 0.000 for PD-L1). Results above was confirmed in the discovery cohort. The increased CD8 and decreased HHLA2 expression levels were associated with long disease-free survival in lung adenocarcinoma (P = 0.000 for CD8 expression and P = 0.004 for HHLA2 expression).Conclusions: B7-H4 and HHLA2 are promising immune targets for lung adenocarcinoma, especially for patients with EGFR mutation.