Department of Thoracic Surgery I, The Yunnan Cancer Hospital, Kunming, China.
Department of Imaging at Kunming Tongren Hospital, Kunming, China.
Front Immunol. 2023 Feb 28;14:1012166. doi: 10.3389/fimmu.2023.1012166. eCollection 2023.
China's southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing.
Tissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy.
In cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, = 0.04; HR 0.23, 0.08 to 0.66, < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, < 0.01; HR 0.22, 0.07 to 0.66, < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, = 0.04; HR 0.50, 0.26 to 0.98, = 0.04) and OS (HR 0.58, 0.35 to 0.96, = 0.03; HR 0.48, 0.25 to 0.93, = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, = 0.01), OS (HR 0.33, 0.10 to 1.13, < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, 0.01) to immunotherapy than other populations.
These findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.
中国西南部的曲靖地区，非小细胞肺癌（NSCLC）发病率和相关死亡率较高。本研究旨在揭示免疫相关预后标志物（IRPS）对曲靖地区晚期 NSCLC 的影响。
回顾性评估 37 名晚期 NSCLC 患者的独立队列组织标本，以确定下一代测序（NGS）估计的 IRPS 与临床结局之间的关系。为了比较组织中的 IRPS 和曲靖与非曲靖人群的临床结局，我们分析了来自癌症基因组图谱（TCGA）数据库的 23 名晚期 NSCLC 患者的数据集。此外，还回顾性分析了 111 名血液标本的独立队列，以确定 IRPS 与临床结局之间的关系。最后，我们评估了血液 IRPS 在分类 24 名可能受益于免疫治疗的晚期 NSCLC 患者中的效用。
在队列 1 中，曲靖人群中 tTMB-H（≥10 个突变/Mb）或 KRAS 突变与无进展生存期（PFS）较短（HR 0.37，0.14 至 0.97， = 0.04；HR 0.23，0.08 至 0.66， < 0.01）和总生存期（OS）（HR 0.05，0.01 至 0.35， < 0.01；HR 0.22，0.07 至 0.66， < 0.01）相关。在曲靖人群的队列 2 中，bTMB-H（≥6 个突变/Mb）和 KRAS 突变与 PFS（HR 0.59，0.36 至 0.99， = 0.04；HR 0.50，0.26 至 0.98， = 0.04）和 OS（HR 0.58，0.35 至 0.96， = 0.03；HR 0.48，0.25 至 0.93， = 0.03）相关。值得注意的是，与其他人群相比，曲靖人群中 bTMB-H 的 PFS（HR 0.32，0.09 至 1.09， = 0.01）、OS（HR 0.33，0.10 至 1.13， < 0.01）和客观缓解率（ORR）（83.3% vs. 14.3% vs. 20.0%，0.01）更高。
这些发现表明，tTMB、bTMB 和 KRAS 突变似乎是独立验证的 IRPS，可预测曲靖地区晚期 NSCLC 患者的临床结局，bTMB 可作为预测曲靖地区晚期 NSCLC 患者接受抗 PD-1 治疗临床获益的可靠 IRPS。
