Department of Research, Tumor Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy.
Department of Applied Research and Technical Development, Medical Statistics and Biometry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
BMC Cancer. 2018 Sep 18;18(1):899. doi: 10.1186/s12885-018-4772-0.
Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. During this process, bi-directional communication among tumor cells and cancer associated fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling. As a result of this dynamic process, soluble ECM proteins can be released into the bloodstream and may represent novel circulating biomarkers useful for cancer diagnosis. The aim of the present study was to measure the levels of three circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples of lung cancer patients and in healthy heavy-smokers controls and test whether such measurements have diagnostic or prognostic value.
Gene expression profiling of lung fibroblasts isolated from paired normal and cancer tissue of NSCLC patients was performed by gene expression microarrays. The prioritization of the candidates for the study of circulating proteins in plasma was based on the most differentially expressed genes in cancer associated fibroblasts. Soluble ECM proteins were assessed by western blot in the conditioned medium of lung fibroblasts and by ELISA assays in plasma samples.
Plasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n = 57 each) and SPARC (n = 90 each). Higher plasma levels of COL10A1 were detected in patients (p ≤ 0.001), a difference that was driven specifically by females (p < 0.001). No difference in COL11A1 levels between patients and controls was found. SPARC levels were also higher in plasma patients than controls (p < 0.001) with good performance in discriminating the two groups (AUC = 0.744). No significant association was observed between plasma proteins levels and clinicopathological features or survival.
Soluble factors related to proficient tumor-stroma cross-talk are detectable in plasma of primary lung cancer patients and may represent a valuable complementary diagnostic tool to discriminate lung cancer patients from healthy heavy-smokers individuals as shown for the SPARC protein.
癌细胞与周围微环境的相互作用是癌症进展的关键决定因素。在这个过程中，肿瘤细胞与癌相关成纤维细胞（CAF）之间的双向交流调节细胞外基质（ECM）的沉积和重塑。由于这个动态过程，可溶性 ECM 蛋白可以释放到血液中，并且可能代表用于癌症诊断的新型循环生物标志物。本研究的目的是测量肺癌患者和健康重度吸烟者对照者血浆样本中三种循环 ECM 相关蛋白（COL11A1、COL10A1 和 SPARC）的水平，并检验这些测量值是否具有诊断或预后价值。
通过基因表达微阵列对非小细胞肺癌（NSCLC）患者配对的正常和癌组织中分离的肺成纤维细胞进行基因表达谱分析。根据在癌相关成纤维细胞中差异表达最明显的基因，对循环蛋白在血浆中的研究进行了候选物的优先级排序。通过 Western blot 在肺成纤维细胞的条件培养基中以及通过 ELISA 测定在血浆样本中评估可溶性 ECM 蛋白。
对来自肺癌患者和健康重度吸烟者对照者的血浆样本进行了 COL11A1 和 COL10A1（n=57 例）和 SPARC（n=90 例）水平的检测。患者血浆中 COL10A1 水平升高（p≤0.001），这一差异主要由女性驱动（p<0.001）。未发现患者与对照者之间 COL11A1 水平存在差异。患者血浆中 SPARC 水平也高于对照者（p<0.001），且在区分两组方面表现良好（AUC=0.744）。未观察到血浆蛋白水平与临床病理特征或生存之间存在显著相关性。
与肿瘤-基质交叉对话相关的可溶性因子可在原发性肺癌患者的血浆中检测到，并且可能代表一种有价值的补充诊断工具，可用于区分肺癌患者和健康重度吸烟者个体，如 SPARC 蛋白所示。
