Univ Rennes, Inserm, Inra, CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Institut NuMeCan (Nutrition Metabolisms and Cancer), UMR_S 1241, Rennes, France.
Br J Cancer. 2020 Jul;123(1):72-80. doi: 10.1038/s41416-020-0863-1. Epub 2020 May 7.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer worldwide, as a result of a late diagnosis and limited therapeutic options. Tumour microenvironment (or stroma) plays a key role in cancer onset and progression and constitutes an intrinsic histological hallmark of PDAC. Thus we hypothesised that relevant prognostic biomarkers and therapeutic targets can be identified in the stroma.
Laser microdissection of the stroma from freshly frozen PDAC was combined to gene expression profiling. Protein expression of candidate biomarkers was evaluated by immunohistochemistry on tissue microarrays (n = 80 tumours) and by ELISA in plasma samples (n = 51 patients).
A signature made of 1256 genes that significantly discriminate the stroma from the non-tumour fibrous tissue was identified. Upregulated genes were associated with inflammation and metastasis processes and linked to NF-Kappa B and TGFβ pathways. TMA analysis validated an increased expression of SFN, ADAMTS12 and CXCL3 proteins in the stroma of PDAC. Stromal expression of SFN was further identified as an independent prognostic factor of overall (p = 0.003) and disease-free survival (DFS) (p = 0.034). SFN plasma expression was significantly associated with reduced DFS (p = 0.006).
We demonstrated that gene expression changes within the stroma of PDAC correlate with tumour progression, and we identified Stratifin as a novel independent prognostic biomarker.
胰腺导管腺癌（PDAC）是一种全球致命的癌症，由于诊断较晚和治疗选择有限。肿瘤微环境（或基质）在癌症的发生和进展中起着关键作用，构成 PDAC 的固有组织学特征。因此，我们假设可以在基质中识别出相关的预后生物标志物和治疗靶点。
对新鲜冷冻的 PDAC 基质进行激光微切割，结合基因表达谱分析。候选生物标志物的蛋白表达通过组织微阵列（n=80 个肿瘤）的免疫组织化学和血浆样本（n=51 个患者）的 ELISA 进行评估。
确定了一个由 1256 个基因组成的特征，这些基因可以显著区分基质与非肿瘤纤维组织。上调的基因与炎症和转移过程相关，并与 NF-Kappa B 和 TGFβ 途径相关。TMA 分析验证了 SFN、ADAMTS12 和 CXCL3 蛋白在 PDAC 基质中的表达增加。SFN 在基质中的表达进一步被确定为总生存期（p=0.003）和无病生存期（DFS）（p=0.034）的独立预后因素。SFN 血浆表达与降低的 DFS 显著相关（p=0.006）。
我们证明了 PDAC 基质内的基因表达变化与肿瘤进展相关，并确定 Stratifin 为一种新的独立预后生物标志物。
