Department of Oncology, Renmin Hospital of Wuhan University, 238th Jiefang Road, Wuhan, 430060, China.
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Biol Sex Differ. 2021 Dec 4;12(1):64. doi: 10.1186/s13293-021-00406-y.
Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer. Compared with male LUAD patients, female patients have a higher incidence, but better long-term survival rate, with unknown reasons. In this study, we aimed to explore the effect of sex differences on immune cell infiltration in lung tumor microenvironment (TME), and tried to clarify the reasons for the different clinical characteristics of male and female LUAD patients, by conducting a comparative analysis of the TME.
Using ESTIMATE algorithm, we calculated immune and stromal scores of tumor samples downloaded from TCGA database according to immune or stromal components in TME. GO and KEGG enrichment analysis were conducted to reveal biological processes of these intersecting genes of high- and low-score groups. Cox regression analysis and protein-protein interaction (PPI) network analysis were performed to screen immune-related prognostic genes in female (CCR2, LCP2, and PTPRC) and male (BTK and CCR2) patients. Kaplan-Meier survival analysis was used to evaluate prognostic value of these identified genes. Mann-Whitney test was used to compare various indicators of male patients and female patients. The main results were subsequently validated in 420 cases from GSE72094.
304 and 368 intersecting genes were identified in female and male patients, respectively. The immune score ranged from -943.17 to 3229.35 among female patients and from -541.75 to 3441.78 among male patients. The stromal score ranged from -1790.23 to 2097.27 among female patients and from -1786.94 to 1722.70 among male patients. The immune and stromal scores of women were higher than those of men (p < 0.05). CCR2, LCP2 and PTPRC were identified as the most important immune-related prognostic genes in female LUAD patients. BTK and CCR2 were identified as the most important immune-related prognostic genes in male LUAD patients. Female patients had a higher proportion of memory B cells than that of male patients, while the percentage of T cells CD4 naïve and resting NK cells was lower in female patients (p < 0.05).
This study comprehensively compared the differences in tumor immune microenvironment between male and female LUAD patients, and identified prognosis-related genes for patients of different sexes.
肺腺癌（LUAD）是肺癌最重要的亚型之一。与男性 LUAD 患者相比，女性患者的发病率更高，但长期生存率更好，原因不明。在这项研究中，我们旨在通过对肿瘤微环境（TME）中的免疫细胞浸润进行比较分析，探讨性别差异对肺肿瘤微环境中免疫细胞浸润的影响，并试图阐明男性和女性 LUAD 患者临床特征不同的原因。
使用 ESTIMATE 算法，根据 TME 中的免疫或基质成分，计算 TCGA 数据库中下载的肿瘤样本的免疫和基质评分。GO 和 KEGG 富集分析用于揭示高、低评分组这些交集基因的生物学过程。Cox 回归分析和蛋白质-蛋白质相互作用（PPI）网络分析用于筛选女性（CCR2、LCP2 和 PTPRC）和男性（BTK 和 CCR2）患者的免疫相关预后基因。Kaplan-Meier 生存分析用于评估这些鉴定基因的预后价值。Mann-Whitney 检验用于比较男性患者和女性患者的各种指标。随后在 GSE72094 中 420 例患者中验证了主要结果。
分别在女性和男性患者中鉴定出 304 个和 368 个交集基因。女性患者的免疫评分范围为-943.17 至 3229.35，男性患者的免疫评分范围为-541.75 至 3441.78。女性患者的基质评分范围为-1790.23 至 2097.27，男性患者的基质评分范围为-1786.94 至 1722.70。女性患者的免疫和基质评分均高于男性患者（p<0.05）。CCR2、LCP2 和 PTPRC 被鉴定为女性 LUAD 患者最重要的免疫相关预后基因。BTK 和 CCR2 被鉴定为男性 LUAD 患者最重要的免疫相关预后基因。女性患者记忆 B 细胞的比例高于男性患者，而女性患者 CD4 幼稚 T 细胞和静止 NK 细胞的比例较低（p<0.05）。
本研究全面比较了男性和女性 LUAD 患者肿瘤免疫微环境的差异，并鉴定了不同性别患者的预后相关基因。
