■分子生物标志物正在重塑患者分层和治疗决策,然而,它们的确切使用和最佳实施仍然不确定。瘤内异质性(ITH),在各种条件下具有预后价值的研究兴趣日益增加的领域,在某些非小细胞肺癌(NSCLC)亚型中缺乏明确的临床相关性。探索ITH与肿瘤突变负荷(TMB)之间的关系至关重要,因为它们的相互作用可能揭示不同的患者亚组。这项研究评估了ITH-TMB动态如何影响NSCLC两种主要组织学亚型的预后。鳞状细胞和腺癌,特别关注早期病例,以满足其高度未满足的临床需求。
■我们根据ITH和TMB对来自癌症基因组图谱(TCGA)的741例早期NSCLC患者进行分层,并评估临床结果的差异。此外,我们比较了高和低ITH组之间的驱动突变和肿瘤微环境(TME)。
■在肺鳞状细胞癌(LUSC)中,高ITH预测无进展生存期(PFS)延长(中位数:21vs.14个月,P=0.01),而在肺腺癌(LUAD)中,高ITH预测PFS降低(中位数:15vs.20个月,P=0.04)。这种关系是由患者的低TMB子集驱动的。此外,我们发现CD8T细胞在表现更好的亚组中富集,无论组织学亚型或ITH状态。
■临床结局存在显着差异,驱动突变,早期非小细胞肺癌患者ITH高和低组间的TME。这些差异可能会对治疗产生影响,需要在其他NSCLC数据集中进一步验证。
UNASSIGNED: Molecular biomarkers are reshaping patient stratification and treatment decisions, yet their precise use and best implementation remain uncertain. Intratumor heterogeneity (ITH), an area of increasing research interest with prognostic value across various conditions, lacks defined clinical relevance in certain non-small cell lung cancer (NSCLC) subtypes. Exploring the relationship between ITH and tumor mutational burden (TMB) is crucial, as their interplay might reveal distinct patient subgroups. This study evaluates how the ITH-TMB dynamic affects prognosis across the two main histological subtypes of NSCLC, squamous cell and adenocarcinoma, with a specific focus on early-stage cases to address their highly unmet clinical needs.
UNASSIGNED: We stratify a cohort of 741 early-stage NSCLC patients from The Cancer Genome Atlas (TCGA) based on ITH and TMB and evaluate differences in clinical outcomes. Additionally, we compare driver mutations and the tumor microenvironment (TME) between high and low ITH groups.
UNASSIGNED: In lung squamous cell carcinoma (LUSC), high ITH predicts an extended progression-free survival (PFS) (median: 21 vs. 14 months, P=0.01), while in lung adenocarcinoma (LUAD), high ITH predicts a reduced PFS (median: 15 vs. 20 months, P=0.04). This relationship is driven by the low TMB subset of patients. Additionally, we found that CD8 T cells were enriched in better-performing subgroups, regardless of histologic subtype or ITH status.
UNASSIGNED: There are significant differences in clinical outcomes, driver mutations, and the TME between high and low ITH groups among early-stage NSCLC patients. These differences may have treatment implications, necessitating further validation in other NSCLC datasets.