Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Clin Lung Cancer. 2022 Jan;23(1):43-51. doi: 10.1016/j.cllc.2021.08.009. Epub 2021 Aug 28.
Programmed death ligand 1 (PD-L1) expression is the current standard biomarker used to predict non-smallcell lung cancer (NSCLC) response to immunotherapy. Gene expression signatures also seem to be related to the response to immunotherapy. Understanding the clinical and prognostic impact of molecular phenotype and tumor features on PD-L1 expression in NSCLC patients may improve the prediction of immunotherapy response.
A total of 819 consecutive surgically resected NSCLC specimens from one institution were analyzed in our study. We determined PD-L1 expression by immunohistochemistry (IHC) using the 22C3 clone and the molecular phenotype by targeted next-generation sequencing with a 68-gene panel.
High PD-L1 expression was significantly associated with wild-type EGFR (P < .001), KRAS mutation (P < .001), ROS1 rearrangement (P < .001), ALK rearrangement (P = .007), RET rearrangement (P = .041) and MET gene alterations (P = .003). Mutations in TP53 and Rb1 were also significantly associated with high PD-L1 expression (both P < .001). High PD-L1 expression was significantly associated with EGFR co-mutation with tumor suppressor genes such as TP53, Rb1, while EGFR mutation alone was not associated with high PD-L1 expression. Poor survival appeared to be linked to high PD-L1 expression or PD-L1 negative expression with concomitant mutations of tumor suppressor genes, especially multiple tumor suppressor genes.
PD-L1 expression is highly correlated with major driver and suppressor gene alterations. High PD-L1 expression and patients with negative PD-L1 expression harboring suppressor gene mutation are associated with poor prognosis in patients with NSCLC.
程序性死亡配体 1（PD-L1）表达是目前预测非小细胞肺癌（NSCLC）对免疫治疗反应的标准生物标志物。基因表达谱似乎也与免疫治疗反应有关。了解分子表型和肿瘤特征对 NSCLC 患者 PD-L1 表达的临床和预后影响，可能有助于预测免疫治疗反应。
我们对一家机构的 819 例连续手术切除的 NSCLC 标本进行了研究。我们使用 22C3 克隆通过免疫组织化学（IHC）确定 PD-L1 表达，并用靶向下一代测序的 68 基因面板确定分子表型。
高 PD-L1 表达与野生型 EGFR（P <.001）、KRAS 突变（P <.001）、ROS1 重排（P <.001）、ALK 重排（P =.007）、RET 重排（P =.041）和 MET 基因改变（P =.003）显著相关。TP53 和 Rb1 的突变也与高 PD-L1 表达显著相关（均 P <.001）。高 PD-L1 表达与 EGFR 与肿瘤抑制基因（如 TP53、Rb1）的共突变显著相关，而 EGFR 突变本身与高 PD-L1 表达无关。较差的生存似乎与高 PD-L1 表达或 PD-L1 阴性表达伴有肿瘤抑制基因的突变有关，尤其是多个肿瘤抑制基因。
PD-L1 表达与主要驱动基因和抑制基因改变高度相关。高 PD-L1 表达和 PD-L1 阴性表达伴有抑制基因突变的患者与 NSCLC 患者的不良预后相关。
