The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) and is found mostly in cartilage. Its role in the tumor microenvironment remains unexplored. To investigate the biomarker potential of a type IX collagen in cancer, an immuno-assay was developed (PRO-C9) and technical assay performance was evaluated for the assessment of serum. PRO-C9 levels were measured in serum samples from 259 patients with various solid tumor types compared to serum levels from 73 healthy controls. PRO-C9 levels were significantly elevated in patients with solid tumors including bladder, breast, colorectal, gastric, head and neck, lung, melanoma, ovarian, pancreatic, and renal compared to levels in healthy controls (p< 0.05–p< 0.0001). PRO-C9 could discriminate between patients with cancer and healthy controls, with the area under the receiver operating characteristic values ranging from 0.58 to 0.86 (p< 0.3–p< 0.0001), indicating potential diagnostic utility. This study suggests that type IX collagen turnover is altered in patients with solid tumors and demonstrates the feasibility of using PRO-C9 as a non-invasive serum-based biomarker with relevance in multiple cancer types. Furthermore, these results underscore the potential utility of PRO-C9 to better elucidate the biology of FACITs in cancers.
纤维化肿瘤微环境以其复杂的细胞外基质为特征，包含多种功能各异且生物标志物潜力尚未被充分探索的胶原蛋白。IX型胶原属于低丰度胶原家族，即具有间断三螺旋结构的原纤维相关胶原，主要存在于软骨组织中。其在肿瘤微环境中的作用尚未明确。为探究IX型胶原在癌症中的生物标志物潜力，本研究开发了一种免疫检测方法（PRO-C9），并评估了该技术用于血清检测的分析性能。研究检测了259例不同实体瘤患者与73例健康对照者的血清样本，结果显示：膀胱癌、乳腺癌、结直肠癌、胃癌、头颈癌、肺癌、黑色素瘤、卵巢癌、胰腺癌及肾癌患者的血清PRO-C9水平均显著高于健康对照组（p<0.05–p<0.0001）。PRO-C9能够有效区分癌症患者与健康对照者，受试者工作特征曲线下面积范围为0.58至0.86（p<0.3–p<0.0001），显示出潜在的诊断价值。本研究表明实体瘤患者的IX型胶原代谢发生改变，并证实PRO-C9作为无创血清生物标志物在多种癌症类型中具有应用可行性。此外，这些结果凸显了PRO-C9在进一步阐明FACITs家族胶原在癌症中生物学功能的潜在价值。
Type IX Collagen Turnover Is Altered in Patients with Solid Tumors
肿瘤(癌症)患者之家