Cancer Center, Daping Hospital and Army Medical Center of PLA, Army Medical University, No.10 Changjiangzhi Rd, Yuzhong District, Chongqing, People's Republic of China.
The 75th Group Army Hospital, Dali, Yunnan, People's Republic of China.
Clin Transl Oncol. 2023 Jun;25(6):1767-1778. doi: 10.1007/s12094-023-03074-z. Epub 2023 Feb 5.
Approximately, 45-65% stage I non-small cell lung cancer (NSCLC) patients with surgical resection relapse within 5 years. Therefore, it is urgent to identify the predictors involved in the relapse of stage I NSCLC.
METHODS/PATIENTS: Targeted sequencing was used to examine the mutation of tumor tissues and matched adjacent normal tissues from 35 patients with stage I lung adenocarcinoma (LUAD). Then, tissue microarrays containing tumor tissues from 149 stage I LUAD patients were used to assess protein expression of frequently mutated genes by immunohistochemistry. COX regression model was used to evaluate the impacts of frequently mutated genes and their protein expression on relapse-free survival (RFS) in stage I LUAD.
Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15-1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54-6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance.
大约有 45-65%的 I 期非小细胞肺癌（NSCLC）患者在手术后 5 年内复发。因此，迫切需要确定与 I 期 NSCLC 复发相关的预测因子。
方法/患者：对 35 例 I 期肺腺癌（LUAD）患者的肿瘤组织和配对的相邻正常组织进行靶向测序。然后，使用包含 149 例 I 期 LUAD 患者肿瘤组织的组织微阵列，通过免疫组织化学评估频繁突变基因的蛋白表达。COX 回归模型用于评估频繁突变基因及其蛋白表达对 I 期 LUAD 无复发生存（RFS）的影响。
在这 35 名患者中，在 161 个基因中鉴定出 329 个非同义体细胞变异。EGFR、TP53、LRP1B、RBM10、KRAS、NTRK3、RB1、ALK、APC、FAT2、KEAP1、MED12 和 MLL3 被描述为突变频率超过 10%的常见突变基因。在手术后 1 年内，携带 KRAS 突变的患者复发更多。对于 149 例 I 期患者中这些频繁突变基因的表达，多变量 Cox 回归分析表明，RBM10 的表达与所有患者的 RFS 呈正相关（HR 0.40，95%CI 0.15-1.0，p=0.052），而 APC 的表达与携带 EGFR 突变的患者的 RFS 呈负相关（HR 3.10，95%CI 1.54-6.26，p=0.002）。KRAS 突变或 RBM10 低表达的 I 期 LUAD 患者倾向于接受更多积极干预，而不仅仅是疾病监测。
