Department of General Surgery, the Third Affiliated Hospital of Southern Medical University, 183 Zhongshan Avenue West, Tianhe District, Guangzhou, 510630, Guangdong, China.
Department of Hepatobiliary surgery, the Third Affiliated Hospital of Southern Medical University, 183 Zhongshan Avenue West, Tianhe District, Guangzhou, 510630, Guangdong, China.
J Transl Med. 2024 Nov 14;22(1):1023. doi: 10.1186/s12967-024-05857-6.
Cholangiocarcinoma (CCA) is an aggressive malignancy with limited treatment options and poor prognosis. Platelet-Derived Growth Factor CC (PDGF-CC) has been implicated in the progression of various tumors, but its specific role in CCA is not well understood. This study aims to investigate the expression and function of PDGF-CC in CCA and evaluate its potential as a therapeutic target.
We conducted gene expression analysis using the GEPIA database to compare PDGF-CC mRNA levels in CCA tissues and normal tissues. Serum samples from CCA patients were analyzed for PDGF-CC protein levels, and immunohistochemistry was used to assess PDGF-CC expression in tissue samples. The impact of PDGF-CC on CCA cell behavior was examined by knocking out PDGF-CC in HuCCT1 and QBC939 cell lines, followed by assessments of cell proliferation, migration, invasion, and colony formation in vitro. Additionally, the effects of PDGF-CC knockout were evaluated in xenograft models. The therapeutic potential of PDGF-CC inhibition was further explored using pharmacological inhibitors and antibodies.
PDGF-CC mRNA and protein levels were significantly elevated in CCA tissues and patient sera compared to normal controls. Immunohistochemical analysis confirmed increased PDGF-CC expression in CCA tissues. High PDGF-CC expression correlated with poor overall survival in CCA patients, as shown by Kaplan-Meier analysis. Functional assays revealed that PDGF-CC knockout significantly reduced proliferation, migration, invasion, and colony formation in HuCCT1 and QBC939 cells, the lines with the highest PDGF-CC levels. In vivo, PDGF-CC knockout markedly decreased tumor growth in xenograft models. Pharmacological inhibition of PDGF-CC mirrored the effects of genetic knockout, suggesting it as a viable therapeutic strategy.
This study underscores the critical role of PDGF-CC in CCA progression and supports the potential of PDGF-CC inhibitors as a therapeutic approach. Given the association between high PDGF-CC expression and poor prognosis, targeting PDGF-CC may improve outcomes for CCA patients. Further clinical investigations are warranted to develop PDGF-CC-targeted therapies for CCA.
胆管癌（CCA）是一种侵袭性恶性肿瘤，治疗选择有限，预后较差。血小板衍生生长因子 CC（PDGF-CC）已被牵连到各种肿瘤的进展中，但它在 CCA 中的具体作用尚不清楚。本研究旨在探讨 PDGF-CC 在 CCA 中的表达和功能，并评估其作为治疗靶点的潜力。
我们使用 GEPIA 数据库进行基因表达分析，比较 CCA 组织和正常组织中 PDGF-CC mRNA 水平。分析 CCA 患者的血清样本中 PDGF-CC 蛋白水平，并通过免疫组织化学评估组织样本中 PDGF-CC 的表达。通过敲除 HuCCT1 和 QBC939 细胞系中的 PDGF-CC，研究 PDGF-CC 对 CCA 细胞行为的影响，然后在体外评估细胞增殖、迁移、侵袭和集落形成。此外，还在异种移植模型中评估了 PDGF-CC 敲除的效果。进一步使用药理学抑制剂和抗体探索 PDGF-CC 抑制的治疗潜力。
与正常对照组相比，CCA 组织和患者血清中的 PDGF-CC mRNA 和蛋白水平显著升高。免疫组织化学分析证实 CCA 组织中 PDGF-CC 表达增加。Kaplan-Meier 分析显示，高 PDGF-CC 表达与 CCA 患者的总生存率降低相关。功能测定显示，PDGF-CC 敲除显著降低了 HuCCT1 和 QBC939 细胞中增殖、迁移、侵袭和集落形成，这些细胞系中的 PDGF-CC 水平最高。在体内，PDGF-CC 敲除显著抑制异种移植模型中的肿瘤生长。PDGF-CC 的药理学抑制反映了基因敲除的效果，表明这是一种可行的治疗策略。
本研究强调了 PDGF-CC 在 CCA 进展中的关键作用，并支持 PDGF-CC 抑制剂作为一种治疗方法的潜力。鉴于高 PDGF-CC 表达与预后不良相关，靶向 PDGF-CC 可能改善 CCA 患者的结局。需要进一步的临床研究来开发针对 CCA 的 PDGF-CC 靶向治疗。
