Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Emergency, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Medicine (Baltimore). 2024 Feb 23;103(8):e36770. doi: 10.1097/MD.0000000000036770.
Little is known about the relationship between programmed cell death-ligand 1 (PD-L1) expression and histologic and genetic features in real-world Chinese non-small cell lung cancer patients. From November 2017 to June 2019, tumor tissues were collected from 2674 non-small cell lung cancer patients. PD-L1 expression was detected with immunohistochemistry using the 22C3 and SP263 antibodies, and patients were stratified into subgroups based on a tumor proportion score of 1%, 1% to 49%, and ≥ 50%. Genetic alterations were profiled using targeted next-generation sequencing. In the total population, 50.5% had negative PD-L1 expression (tumor proportion score < 1%), 32.0% had low-positive expression (1%-49%), and 17.5% had high-positive expression (≥50%). The PD-L1 positive rate was 39.0% in squamous cell carcinomas and 53.6% in adenocarcinomas. PD-L1 expression was higher in squamous cell carcinomas (P < .001) and lower in adenocarcinomas (P < .001). Of the overall patient population, 11.2% had Kirsten rat sarcoma viral oncogene (KRAS) mutations, 44.9% had epidermal growth factor receptor (EGFR) mutations, 2.1% had BRAF V600E mutations, 0.3% had MET exon 14 skipping mutations, 5.4% had anaplastic lymphoma kinase translocations, and 0.9% had ROS proto-oncogene 1 translocations. Patients carrying ROS proto-oncogene 1 translocations (P = .006), KRAS (P < .001), and MET (P = .023) mutations had significantly elevated expression of PD-L1, while those harboring EGFR (P < .001) mutations had lower PD-L1 expression. In our study, PD-L1 expression was significantly higher in squamous cell carcinomas and lower in adenocarcinomas, and was positively associated with MET and KRAS mutations, as well as the wild-type EGFR gene state. Nonetheless, additional studies are needed to further validate those associations and determine the clinical significance for immune checkpoint inhibitors of these factors.
在中国非小细胞肺癌患者的真实世界中，关于程序性死亡配体 1（PD-L1）表达与组织学和遗传学特征之间的关系知之甚少。本研究从 2017 年 11 月至 2019 年 6 月共收集了 2674 例非小细胞肺癌患者的肿瘤组织。采用 22C3 和 SP263 抗体通过免疫组织化学检测 PD-L1 的表达，并根据肿瘤比例评分（TPS）将患者分为 TPS<1%、1%～49%和≥50%三个亚组。采用靶向二代测序分析遗传改变。在总人群中，50.5%的患者 PD-L1 表达为阴性（TPS<1%），32.0%为低表达（1%～49%），17.5%为高表达（≥50%）。鳞状细胞癌的 PD-L1 阳性率为 39.0%，腺癌为 53.6%。鳞状细胞癌中 PD-L1 的表达更高（P<0.001），腺癌中则更低（P<0.001）。在总患者人群中，11.2%的患者存在 Kirsten 大鼠肉瘤病毒致癌基因（KRAS）突变，44.9%的患者存在表皮生长因子受体（EGFR）突变，2.1%的患者存在 BRAF V600E 突变，0.3%的患者存在 MET 外显子 14 跳跃突变，5.4%的患者存在间变性淋巴瘤激酶易位，0.9%的患者存在 ROS 原癌基因 1 易位。ROS 原癌基因 1 易位（P=0.006）、KRAS（P<0.001）和 MET（P=0.023）突变的患者 PD-L1 表达显著升高，而 EGFR（P<0.001）突变的患者 PD-L1 表达则降低。在本研究中，PD-L1 表达在鳞状细胞癌中显著升高，在腺癌中降低，与 MET 和 KRAS 突变以及野生型 EGFR 基因状态呈正相关。然而，需要进一步的研究来进一步验证这些关联，并确定这些因素对免疫检查点抑制剂的临床意义。
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