FAM83A: A Prospective Diagnostic Biomarker with Immunological Relevance in Lung Adenocarcinoma- Associated Malignant Pleural Effusion

Author:

Liu Hangfeng1,Yao Jia2,Liu Yulan1,Wu Liping1,Tan Zhiwei1,Hu Jie1,Chen Shigao1,Zhang Xiaolin1,Cheng Shuanghua1

Affiliation:

1. China National Nuclear Corporation 416 Hospital

2. West China Biomedical Big Data Center, West China Hospital, Sichuan University

Abstract

Abstract

Background: Malignant pleural effusion (MPE) is most frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure than pleural biopsy. Therefore, it is urgently required to discover new effective biomarkers for LUAD-associated pleural fluid cytology. Methods: mRNA sequencing and clinical data of LUAD were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were carried out on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA were assessed in 94 pairs of LUAD tumor and adjacent normal tissues, as well as in pleural effusion cell blocks obtained from 40 LUAD and 21 non-neoplastic patients, using immunohistochemistry. Results:Bioinformatics analysis demonstrated that FAM83A was screened out as a candidate biomarker for pleural fluid cytology due to its obvious difference in LUAD tissues and its influence on overall or disease-free survival, and histological grade. Immunohistochemistry showed that FAM83A expression was amplified in LUAD tissues compared with paired normal tissues in 89 out of 94 pairs. Immune cell infiltration analysis revealed that FAM83A expression was significantly correlated with immune cell infiltration, such as a positive association with macrophage infiltration. Meanwhile, FAM83A staining was positive in 37 cases of LUAD pleural effusions, and was negative in 20 cases of non-neoplastic pleural effusions. Additionally, the expression pattern of FAM83A in LUAD pleural effusions was relatively consistent with that of TFF-1 and NapsinA, and was even a little stronger in some LUAD pleural effusions that were weakly positive or negative for TTF1 or NapsinA. Conclusions: Our work reveals FAM83A as a promising immune-related biomarker not only in LUAD biopsy specimens but also in LUAD pleural effusion. Our finding is of importance for providing a new and effective option for pleural fluid cytology.

Publisher

Research Square Platform LLC

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