Department of Respiratory Medicine, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Lung Cancer. 2023 Jul;181:107255. doi: 10.1016/j.lungcan.2023.107255. Epub 2023 May 20.
Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported.
Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression.
Among 12,484 lung cancer patients screened, 66 were found with MSI-H, the proportion was as low as 0.5%. Compared with Microsatellite stability (MSS), TMB was higher in MSI-H lung cancer patients, while PD-L1 expression showed no considerable difference between MSI-H and MSS. After propensity score matching, compared with MSS, the most common companion mutations in MSI-H were TP53, BRCA2, TGFBR2, PTEN and KMT2C. In MSI-H lung adenocarcinoma with EGFR mutation, TGFBR2 and ERBB2 had higher mutation frequency than in MSS.
The current study reveals the genetic characteristics of MSI-H lung cancer, which advanced our understanding of MSI-H lung cancer.
微卫星不稳定性（MSI）是首个被批准用于指导 MSI 高（MSI-H）实体瘤免疫检查点抑制剂治疗的泛癌生物标志物。在肺癌中，MSI-H 的频率非常低，MSI-H 肺癌的遗传特征和预后很少有报道。
使用下一代测序和免疫组织化学检测 MSI 状态、肿瘤突变负担（TMB）和 PD-L1 表达。
在筛选的 12484 例肺癌患者中，发现 66 例 MSI-H，比例低至 0.5%。与微卫星稳定（MSS）相比，MSI-H 肺癌患者的 TMB 更高，而 PD-L1 表达在 MSI-H 和 MSS 之间没有明显差异。经过倾向评分匹配后，与 MSS 相比，MSI-H 中最常见的伴随突变是 TP53、BRCA2、TGFBR2、PTEN 和 KMT2C。在 EGFR 突变的 MSI-H 肺腺癌中，TGFBR2 和 ERBB2 的突变频率高于 MSS。
本研究揭示了 MSI-H 肺癌的遗传特征，加深了我们对 MSI-H 肺癌的认识。
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