Objectives

The purpose of this study was to investigate the clinicopathological, gene expression and genetic features of stage I lung adenocarcinoma with necrosis.

Methods

We retrospectively reviewed 521 cases with pathologic stage I lung adenocarcinoma resected by lobectomy and lymph node dissection. We calculated the ratio of tumor necrotic area by digital image analysis and investigated the relationship between tumor necrosis and prognosis. Furthermore, we analyzed the differentially expressed genes between cases with and without necrosis using The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) dataset. Using whole exon sequencing data (n = 97), we examined whether tumor necrosis correlates with single nucleotide variants (SNVs) and driver mutations.

Results

Eighty four (16%) cases of the study cohort had tumor necrosis. The presence of necrosis significantly correlated with poorer prognosis (5-year overall survival: 91.9% vs. 75.4%, p < 0.001; 5-year recurrence-free survival: 86.0% vs. 59.0%, p < 0.001); however, the ratio of necrotic area did not correlate with prognosis. In multivariable analysis, invasive component size, vascular invasion, and tumor necrosis were independently associated with a higher risk of recurrence (hazard ratio, 1.652; 95% confidence interval, 1.033–2.641; p = 0.036). Gene expression analysis of TCGA stage I lung adenocarcinoma revealed enrichment of biological processes, such as cell cycle and response to hypoxia, in cases with necrosis. The cases with tumor necrosis had more SNVs than those without tumor necrosis (p = 0.027), especially in smokers.

Conclusion

Stage I lung adenocarcinoma with tumor necrosis has worse prognosis than that without, and has distinct clinicopathological features in terms of gene expression and genetic features.

中文翻译：

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I期肺腺癌坏死的临床病理、基因表达和遗传特征

目标

本研究的目的是调查 I 期肺腺癌坏死的临床病理、基因表达和遗传特征。

方法

我们回顾性分析了 521 例经肺叶切除和淋巴结清扫术切除的病理 I 期肺腺癌病例。我们通过数字图像分析计算了肿瘤坏死面积的比例，并研究了肿瘤坏死与预后的关系。此外，我们使用癌症基因组图谱肺腺癌（TCGA-LUAD）数据集分析了有坏死和无坏死病例之间的差异表达基因。使用全外显子测序数据（n = 97），我们检查了肿瘤坏死是否与单核苷酸变异（SNV）和驱动突变相关。

结果

研究队列中的 84 例 (16%) 病例有肿瘤坏死。坏死的存在与较差的预后显着相关（5 年总生存率：91.9% 与 75.4%，p < 0.001；5 年无复发生存率：86.0% 与 59.0%，p < 0.001）；然而，坏死面积的比例与预后无关。在多变量分析中，侵入性成分大小、血管侵犯和肿瘤坏死与较高的复发风险独立相关（风险比，1.652；95% 置信区间，1.033–2.641；p = 0.036）。TCGA I 期肺腺癌的基因表达分析揭示了在坏死病例中生物过程的富集，例如细胞周期和对缺氧的反应。肿瘤坏死的病例比没有肿瘤坏死的病例具有更多的 SNV（p = 0.027），尤其是在吸烟者中。

结论

有肿瘤坏死的Ⅰ期肺腺癌预后比无肿瘤坏死的肺腺癌差， 在基因表达和遗传特征方面具有明显的临床病理特征。