Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China.
Aging (Albany NY). 2020 Nov 26;12(23):24333-24344. doi: 10.18632/aging.202238.
Chemotherapy resistance eventually develops in patients with gastric cancer (GC). Intra-tumoral heterogeneity (ITH) refers to the intercellular genetic variations and phenotypic diversity that affect responses to drug therapy. We measured ITH using mutant-allele tumor heterogeneity (MATH) derived from whole-exome sequencing data of patients with GC in The Cancer Genome Atlas (TCGA) database. The study included 385 patients from the TCGA database with available data regarding gastrectomy, survival, and whole-exome sequencing. Further analysis was performed in 171 GC patients with available data regarding adjuvant chemotherapy. Multiple factor analysis showed that MATH was an independent predictor of OS (hazard ratio [HR], 1.432; 95% confidence interval [CI], 1.073-1.913; = 0.015) in patients with GC. Moreover, MATH was also an independent predictor of OS among the 171 GC patients who received adjuvant chemotherapy (HR, 2.016; 95% CI, 1.236-3.289; = 0.005). Pathway enrichment and immune cell analyses revealed significantly higher infiltration by 20 types of immune cells in the low/intermediate group, compared to the group with high MATH scores. In conclusion, low/intermediate MATH scores predicted longer OS, when compared to those with high MATH scores. The immune response was obviously upregulated in patients with GC and low/intermediate MATH scores.
胃癌（GC）患者最终会产生化疗耐药。肿瘤内异质性（ITH）是指影响药物治疗反应的细胞间遗传变异和表型多样性。我们使用从癌症基因组图谱（TCGA）数据库中 GC 患者的全外显子测序数据得出的突变等位基因肿瘤异质性（MATH）来测量 ITH。该研究包括来自 TCGA 数据库的 385 名有胃切除术、生存和全外显子测序数据的患者。进一步对 171 名有辅助化疗数据的 GC 患者进行了分析。多因素分析显示，MATH 是 GC 患者 OS 的独立预测因素（危险比 [HR]，1.432；95%置信区间 [CI]，1.073-1.913；P=0.015）。此外，在接受辅助化疗的 171 名 GC 患者中，MATH 也是 OS 的独立预测因素（HR，2.016；95%CI，1.236-3.289；P=0.005）。通路富集和免疫细胞分析显示，与高 MATH 评分组相比，低/中 MATH 评分组的 20 种免疫细胞浸润明显更高。总之，与高 MATH 评分组相比，低/中 MATH 评分组的 OS 更长。GC 患者和低/中 MATH 评分患者的免疫反应明显上调。
