Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Proteomics Clin Appl. 2023 Sep;17(5):e2300011. doi: 10.1002/prca.202300011. Epub 2023 Mar 1.
Small cell lung cancer (SCLC) is one of the malignant cancers with aggressive progression and poor prognosis. Bronchoalveolar lavage fluid (BALF) has been arising recently as a potential source of biomarkers for lung cancers. In this study, we performed quantitative BALF proteomic analysis to identify potential biomarkers for SCLC.
BALF were collected from tumor-bearing lungs and non-tumor lungs of five SCLC patients. Then, BALF proteomes were prepared for a TMT-based quantitative mass spectrometry analysis. Differentially expressed proteins (DEP) were identified when considering individual variation. Potential SCLC biomarker candidates were validated by immunohistochemistry (IHC). A public database of multiple SCLC cell lines was used to evaluate the correlation of these markers with SCLC subtypes and chemo-drug responses.
We identified 460 BALF proteins in SCLC patients and observed considerable individual variation among the patients. Immunohistochemical analysis and bioinformatics resulted in the identification of CNDP2 and RNPEP as potential subtype markers for ASCL1 and NEUROD1, respectively. In addition, CNDP2 was found to be positively correlated with responses to etoposide, carboplatin, and irinotecan.
BALF is an emerging source of biomarkers, making it useful for the diagnosis and prognosis of lung cancers. We characterized the proteomes of paired BALF samples collected from tumor-bearing and non-tumor lungs of SCLC patients. Several proteins were found elevated in tumor-bearing BALF, and especially CNDP2 and RNPEP appeared to be potential indicators for ASLC1-high and NEUROD1-high subtypes of SCLC, respectively. The positive correlation of CNDP2 with chemo-drug responses would help to make decisions for treatment of SCLC patients. These putative biomarkers could be comprehensively investigated for a clinical use towards precision medicine.
小细胞肺癌（SCLC）是一种恶性肿瘤，具有侵袭性进展和不良预后。支气管肺泡灌洗液（BALF）最近作为肺癌生物标志物的潜在来源受到关注。在本研究中，我们进行了定量 BALF 蛋白质组学分析，以鉴定 SCLC 的潜在生物标志物。
从 5 例 SCLC 患者的肿瘤肺和非肿瘤肺中采集 BALF。然后，为基于 TMT 的定量质谱分析制备 BALF 蛋白质组。考虑个体差异时，鉴定差异表达蛋白（DEP）。通过免疫组织化学（IHC）验证潜在的 SCLC 生物标志物候选物。使用多个 SCLC 细胞系的公共数据库评估这些标志物与 SCLC 亚型和化疗药物反应的相关性。
我们在 SCLC 患者中鉴定出 460 种 BALF 蛋白，观察到患者之间存在相当大的个体差异。免疫组织化学分析和生物信息学结果分别确定 CNDP2 和 RNPEP 为 ASCL1 和 NEUROD1 的潜在亚型标志物。此外，CNDP2 与依托泊苷、卡铂和伊立替康的反应呈正相关。
BALF 是生物标志物的新兴来源，可用于肺癌的诊断和预后。我们对来自 SCLC 患者肿瘤肺和非肿瘤肺的配对 BALF 样本进行了蛋白质组学分析。在肿瘤性 BALF 中发现几种蛋白升高，尤其是 CNDP2 和 RNPEP 分别似乎是 SCLC 的 ASCL1-高和 NEUROD1-高亚型的潜在标志物。CNDP2 与化疗药物反应的正相关有助于为 SCLC 患者的治疗决策提供帮助。这些候选生物标志物可以全面研究，以实现精准医学的临床应用。
