Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200000, China.
Department of Oncology, Shanghai Medical College Fudan University, Shanghai, 200000, China.
Funct Integr Genomics. 2023 Jan 16;23(1):39. doi: 10.1007/s10142-022-00956-3.
Ovarian cancer (OC) is the most common malignant cancer in the female reproductive system. Hypoxia is an important part of tumor immune microenvironment (TIME), which is closely related to cancer progression and could significantly affect cancer metastasis and prognosis. However, the relationship between hypoxia and OC remained unclear. OCs were molecularly subtyped by consensus clustering analysis based on the expression characteristics of hypoxia-related genes. Kaplan-Meier (KM) survival was used to determine survival characteristics across subtypes. Immune infiltration analysis was performed by using Estimation of Stromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) and microenvironment cell populations-counter (MCP-Counter). Differential expression analysis was performed by using limma package. Next, univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to build a hypoxia-related risk score model (HYRS). Mutational analysis was applied to determine genomic variation across the HYRS groups. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to compare the effectiveness of HYRS in immunotherapy prediction. We divided OC samples into two molecular subtypes (C1 and C2 subtypes) based on the expression signature of hypoxia genes. Compared with C1 subtype, there was a larger proportion of poor prognosis genotypes in the C2 subtype. And most immune cells scored higher in the C2 subtype. Next, we obtained a HYRS based on 7 genes. High HYRS group had a higher gene mutation rate, such as TP53. Moreover, HYRS performed better than TIDE in predicting immunotherapy effect. Combined with clinicopathological features, the nomogram showed that HYRS had the greatest impact on survival prediction and a strong robustness.
卵巢癌(OC)是女性生殖系统最常见的恶性肿瘤。缺氧是肿瘤免疫微环境(TIME)的重要组成部分,与癌症的进展密切相关,可显著影响癌症的转移和预后。然而,缺氧与 OC 之间的关系尚不清楚。我们根据缺氧相关基因的表达特征对 OC 进行了共识聚类分析的分子亚型分类。采用 Kaplan-Meier(KM)生存分析确定各亚型的生存特征。通过使用 ESTIMATE 和 MCP-Counter 进行免疫浸润分析。采用 limma 包进行差异表达分析。接下来,采用单变量 Cox 和最小绝对收缩和选择算子(LASSO)回归分析构建与缺氧相关的风险评分模型(HYRS)。突变分析用于确定 HYRS 组的基因组变异。使用 Tumor Immune Dysfunction and Exclusion(TIDE)算法比较 HYRS 在免疫治疗预测中的有效性。我们根据缺氧基因的表达特征将 OC 样本分为两个分子亚型(C1 和 C2 亚型)。与 C1 亚型相比,C2 亚型中预后不良基因型的比例更大。并且 C2 亚型中的大多数免疫细胞评分更高。接下来,我们基于 7 个基因获得了一个 HYRS。高 HYRS 组的基因突变率更高,如 TP53。此外,HYRS 在预测免疫治疗效果方面优于 TIDE。结合临床病理特征,列线图显示 HYRS 对生存预测的影响最大,且具有较强的稳健性。