Yang Kaiyan, Shen Zhaolong, Yin Ning, Quan Jun, Wang Mengwen, Gao Kai
Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, China.
Front Surg. 2022 Apr 25;9:881554. doi: 10.3389/fsurg.2022.881554. eCollection 2022.
Hypoxia plays a major role in various tumor types. However, few studies have concentrated on the prognostic model of hypoxia-related genes in rectal cancer and the effect of hypoxia on neutrophil-mediated immunosuppression. We performed Kaplan-Meier analysis, random survival forest analysis, and Cox regression analysis on 342 hypoxia-related genes, constructed hypoxia score in the Gene Expression Omnibus (GEO) cohort, and verified them in the Cancer Genome Atlas (TCGA) cohort. Then the patients were divided into two groups according to the risk level. The overall survival rate of the high-risk (HRisk) group was significantly higher than that of the low-risk (LRisk) group (GEO, < 0.001; TCGA, = 0.016). Through receiver operating characteristic and decision curve analysis, the nomogram based on hypoxia score has excellent prediction ability. Functional enrichment analysis showed that hypoxia, metastasis, inflammation, immunity, and other related pathways were enriched. The HRisk group was associated with lower tumor purity, higher immune and stromal score, higher neutrophils, and lower activated memory CD4 + T cells. More importantly, the checkpoint of neutrophil-mediated immunosuppression increased in the HRisk group. In conclusion, a hypoxia score based on 5 hypoxia-related genes can be used to predict the prognosis of rectal cancer and ANLN with a cancer-suppressing effect and SRPX (Sushi Repeat Containing Protein X-Linked) with a cancer-promoting effect may be potential therapeutic targets for rectal cancer.
缺氧在多种肿瘤类型中起着重要作用。然而，很少有研究关注直肠癌中缺氧相关基因的预后模型以及缺氧对中性粒细胞介导的免疫抑制的影响。我们对342个缺氧相关基因进行了Kaplan-Meier分析、随机生存森林分析和Cox回归分析，在基因表达综合数据库（GEO）队列中构建了缺氧评分，并在癌症基因组图谱（TCGA）队列中进行了验证。然后根据风险水平将患者分为两组。高风险（HRisk）组的总生存率显著高于低风险（LRisk）组（GEO，<0.001；TCGA，=0.016）。通过受试者工作特征曲线和决策曲线分析，基于缺氧评分的列线图具有出色的预测能力。功能富集分析表明，缺氧、转移、炎症、免疫等相关通路得到富集。HRisk组与较低的肿瘤纯度、较高的免疫和基质评分、较高的中性粒细胞以及较低的活化记忆CD4+T细胞相关。更重要的是，HRisk组中中性粒细胞介导的免疫抑制检查点增加。总之，基于5个缺氧相关基因的缺氧评分可用于预测直肠癌的预后，具有抑癌作用的ANLN和具有促癌作用的SRPX（含寿司重复序列蛋白X连锁）可能是直肠癌潜在的治疗靶点。
