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, China.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Int J Cancer. 2022 Sep 1;151(5):717-729. doi: 10.1002/ijc.34137. Epub 2022 Jun 8.
Pulmonary sarcomatoid carcinoma (PSC) is a unique form of poorly differentiated nonsmall cell lung cancer (NSCLC) and is notorious for its highly malignant nature and dismal prognosis. To introduce effective treatment for PSC patients, precise subtyping of PSC is demanding. In our study, TTF-1 and P40 immunohistochemistry (IHC) staining were applied to 56 PSC patients with multiomics data. According to IHC results, we categorized these patients into three subgroups and profiled their molecular contexture using bioinformatic skills. IHC results classified these patients into three subgroups: TTF-1 positive subgroup (n = 27), P40 positive subgroup (n = 15) and double-negative subgroup (n = 14). Spindle cell samples accounted for 35.71% (5/14) of double-negative patients, higher than others (P = .034). The three subgroups were heterogeneous in the genomic alteration spectrum, showing significant differences in the RTK/RAS pathway (P = .004) and the cell cycle pathway (P = .030). The methylation profile of the double-negative subgroup was between the other two subgroups. In similarity analysis, the TTF-1 and p40 subgroups were closely related to LUAD and LUSC, respectively. The TTF-1 positive subgroup had the highest leukocyte fraction (LF) among several cancer types, and the tumor mutation burden (TMB) of the p40 positive subgroup ranked third in the TMB list, suggesting the applicability of immunotherapy for PSC. The study established a new subtyping method of PSC based on IHC results and reveals three subgroups with distinct molecular features, providing evidence for refined stratification in the treatment of PSC.
肺肉瘤样癌（PSC）是一种独特的低分化非小细胞肺癌（NSCLC）形式，以高度恶性和预后不良而臭名昭著。为了为 PSC 患者引入有效的治疗方法，需要对 PSC 进行精确的亚型分类。在我们的研究中，我们对 56 例 PSC 患者进行了多组学数据分析，并应用 TTF-1 和 P40 免疫组织化学（IHC）染色。根据 IHC 结果，我们将这些患者分为三个亚组，并运用生物信息学技术对其分子特征进行了分析。IHC 结果将这些患者分为三个亚组：TTF-1 阳性亚组（n=27）、P40 阳性亚组（n=15）和双阴性亚组（n=14）。双阴性组中梭形细胞样本占 35.71%（5/14），高于其他组（P=.034）。这三个亚组在基因组改变谱上存在异质性，在 RTK/RAS 途径（P=.004）和细胞周期途径（P=.030）上存在显著差异。双阴性亚组的甲基化谱介于其他两个亚组之间。在相似性分析中，TTF-1 和 p40 亚组分别与 LUAD 和 LUSC 密切相关。TTF-1 阳性亚组在几种癌症类型中具有最高的白细胞分数（LF），而 p40 阳性亚组的肿瘤突变负担（TMB）在 TMB 列表中排名第三，提示免疫疗法对 PSC 的适用性。本研究基于 IHC 结果建立了一种新的 PSC 亚型分类方法，并揭示了三个具有不同分子特征的亚组，为 PSC 的治疗提供了更精细的分层依据。
