关键词: Biomarker FAM83A Immune infiltration Lung adenocarcinoma Malignant pleural effusion

来  源:   DOI:10.1007/s12672-024-01109-7   PDF(Pubmed)

Abstract:
BACKGROUND: Malignant pleural effusion (MPE) is frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure compared to pleural biopsy. Therefore, it is crucial to identify novel effective biomarkers for LUAD-associated pleural fluid cytology.
METHODS: The RNA sequencing (RNA-Seq) and clinical data of LUAD cases were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were performed on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA in 94 paired LUAD and adjacent normal tissues, and in the pleural effusion specimens of 40 LUAD and 21 non-neoplastic patients were evaluated by immunohistochemistry.
RESULTS: FAM83A expression levels were significantly different between the LUAD and normal tissue datasets, and correlated with overall or disease-free survival, and histological grade of the tumors. Furthermore, the in-situ expression of FAM83A was higher in 89/94 LUAD tissues compared to the paired normal tissues. FAM83A expression was significantly correlated with immune cell infiltration, and showed a positive association with macrophage infiltration. In addition, FAM83A staining was positive in 37 LUAD pleural effusion samples, and negative in 20 non-neoplastic pleural effusion samples. The expression pattern of FAM83A in the pleural effusion of LUAD patients was relatively consistent with that of TFF-1 and NapsinA, and even stronger in some specimens that were weakly positive or negative for TTF1/NapsinA.
CONCLUSIONS: FAM83A is a promising immune-related biomarker in LUAD biopsy specimens and pleural fluid, and can distinguish between malignant and benign pleural effusion.
摘要:
背景:在晚期肺腺癌(LUAD)患者中经常观察到恶性胸腔积液(MPE)。与胸膜活检相比,胸膜液细胞学检查是一种侵入性较小的方法。因此,对于LUAD相关的胸水细胞学,确定新的有效生物标志物至关重要.
方法:从TCGA和OncoSG数据库下载了LUAD病例的RNA测序(RNA-Seq)和临床数据。差异基因表达分析,对LUAD数据集进行生存分析和免疫细胞浸润分析.FAM83A的表达水平,TFF-1和NapsinA在94成对的LUAD和邻近的正常组织中,在40例LUAD和21例非肿瘤性患者的胸腔积液标本中,通过免疫组织化学进行了评估。
结果:FAM83A表达水平在LUAD和正常组织数据集之间有显著差异,并与总体或无病生存率相关,和肿瘤的组织学分级。此外,与配对的正常组织相比,FAM83A在89/94LUAD组织中的原位表达更高。FAM83A表达与免疫细胞浸润显著相关,并显示与巨噬细胞浸润呈正相关。此外,37例LUAD胸腔积液中FAM83A染色阳性,20例非肿瘤性胸腔积液标本呈阴性。LUAD患者胸腔积液中FAM83A的表达与TFF-1和NapsinA的表达相对一致。在一些对TTF1/NapsinA呈弱阳性或阴性的标本中甚至更强。
结论:FAM83A是LUAD活检标本和胸腔积液中一种有前途的免疫相关生物标志物,并能区分恶性和良性胸腔积液。
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