Department of Cardiothoracic Surgery, NYU Langone Health, New York, NY.
Experimental Pathology Research Laboratory, Department of Pathology, NYU Langone Health, New York, NY.
J Thorac Cardiovasc Surg. 2024 Sep;168(3):648-657.e8. doi: 10.1016/j.jtcvs.2023.10.047. Epub 2023 Oct 27.
Early-stage lung adenocarcinoma is treated with local therapy alone, although patients with grade 3 stage I lung adenocarcinoma have a 50% 5-year recurrence rate. Our objective is to determine if analysis of the tumor microenvironment can create a predictive model for recurrence.
Thirty-four patients with grade 3 stage I lung adenocarcinoma underwent surgical resection. Digital spatial profiling was used to perform genomic (n = 31) and proteomic (n = 34) analyses of pancytokeratin positive and negative tumor cells. K-means clustering was performed on the top 50 differential genes and top 20 differential proteins, with Kaplan-Meier recurrence curves based on patient clustering. External validation of high-expression genes was performed with Kaplan-Meier plotter.
There were no significant clinicopathologic differences between patients who did (n = 14) and did not (n = 20) have recurrence. Median time to recurrence was 806 days; median follow-up with no recurrence was 2897 days. K-means clustering of pancytokeratin positive genes resulted in a model with a Kaplan-Meier curve with concordance index of 0.75. K-means clustering for pancytokeratin negative genes was less successful at differentiating recurrence (concordance index 0.6). Genes upregulated or downregulated for recurrence were externally validated using available public databases. Proteomic data did not reach statistical significance but did internally validate the genomic data described.
Genomic difference in lung adenocarcinoma may be able to predict risk of recurrence. After further validation, stratifying patients by this risk may help guide who will benefit from adjuvant therapy.
早期肺腺癌仅采用局部治疗，但 3 级 I 期肺腺癌患者有 50%的 5 年复发率。我们的目的是确定肿瘤微环境的分析是否可以建立一个复发的预测模型。
34 例 3 级 I 期肺腺癌患者接受了手术切除。数字空间分析用于对全细胞角蛋白阳性和阴性肿瘤细胞进行基因组（n=31）和蛋白质组（n=34）分析。对前 50 个差异基因和前 20 个差异蛋白进行 K-均值聚类，并根据患者聚类绘制 Kaplan-Meier 复发曲线。通过 Kaplan-Meier 绘图仪对高表达基因进行外部验证。
有（n=14）和无（n=20）复发的患者之间无明显的临床病理差异。复发的中位时间为 806 天；无复发的中位随访时间为 2897 天。全细胞角蛋白阳性基因的 K-均值聚类得到的 Kaplan-Meier 曲线的一致性指数为 0.75。全细胞角蛋白阴性基因的 K-均值聚类在区分复发方面的效果较差（一致性指数为 0.6）。使用可用的公共数据库对复发的上调或下调基因进行了外部验证。蛋白质组学数据未达到统计学意义，但内部验证了描述的基因组数据。
肺腺癌的基因组差异可能能够预测复发的风险。在进一步验证后，根据这种风险对患者进行分层可能有助于指导哪些患者将从辅助治疗中受益。
