Wang Liqiang, Cai Mengdi, Song Ying, Bai Jing, Sun Wenjing, Yu Jingcui, Du Shuomeng, Lu Jianping, Fu Songbin
Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, China.
Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
Front Genet. 2022 Jul 26;13:944492. doi: 10.3389/fgene.2022.944492. eCollection 2022.
Genetic variation has been shown to affect tumor growth and progression, and the temperature at different latitudes may promote the evolution of genetic variation. Geographical data with latitudinal information is of importance to understand the interplay between genetic variants and environmental influence, such as the temperature, in gastric cancer (GC). In this study, we classified the GC samples from The Cancer Genome Atlas database into two groups based on the latitudinal information of patients and found that GC samples with low-latitude had better clinical outcomes. Further analyses revealed significant differences in other clinical factors such as disease stage and grade between high and low latitudes GC samples. Then, we analyzed the genomic and transcriptomic differences between the two groups. Furthermore, we evaluated the activity score of metabolic pathways and infiltrating immune cells in GC samples with different latitudes using the single-sample gene set enrichment analysis algorithm. These results showed that GC samples at low-latitude had lower tumor mutation burden and subclones as well as higher DNA repair activities. Meanwhile, we found that most immune cells were associated with the prognosis of low-latitude GC patients. At last, we constructed and validated an immune-related prognostic model to evaluate the prognosis of GC samples at different latitudes. This study has provided a further understanding of the geographical contribution to GC at the multiomic level and may benefit the individualized treatment of GC patients at different latitudes.
遗传变异已被证明会影响肿瘤的生长和进展,不同纬度的温度可能会促进遗传变异的进化。带有纬度信息的地理数据对于理解胃癌(GC)中遗传变异与环境影响(如温度)之间的相互作用至关重要。在本研究中,我们根据患者的纬度信息将来自癌症基因组图谱数据库的GC样本分为两组,发现低纬度的GC样本具有更好的临床结果。进一步分析显示,高纬度和低纬度GC样本在疾病分期和分级等其他临床因素上存在显著差异。然后,我们分析了两组之间的基因组和转录组差异。此外,我们使用单样本基因集富集分析算法评估了不同纬度GC样本中代谢途径和浸润免疫细胞的活性评分。这些结果表明,低纬度的GC样本具有较低的肿瘤突变负担和亚克隆以及较高的DNA修复活性。同时,我们发现大多数免疫细胞与低纬度GC患者的预后相关。最后,我们构建并验证了一个免疫相关的预后模型,以评估不同纬度GC样本的预后。本研究在多组学水平上进一步加深了对地理因素对GC影响的理解,可能有益于不同纬度GC患者的个体化治疗。