Department of Orthopedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China (mainland).
Department of Orthopedics, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China (mainland).
Med Sci Monit. 2020 Apr 21;26:e923853. doi: 10.12659/MSM.923853.
BACKGROUND The insulin-like growth factor 1 (IGF1) pathway is deeply involved in cell proliferation, including tumorigenesis. Aberrant genetic alterations of IGF1 pathway members were revealed in certain malignancies, including chondrosarcoma (CHS). We proposed that genetic polymorphisms in IGF1 pathways might be associated with susceptibility to tumorigenesis and prognosis of CHS in Chinese populations. MATERIAL AND METHODS We recruited 112 pathologically diagnosed CHS cases and 104 cancer-free controls in this study. There were 5 single-nucleotide polymorphisms of IGF1 pathway members (IGF1R rs2016347, IGF1 rs1520220, IGF1 rs2946834, IGF3BP3 rs2270628, and IGF2 rs4320932) genotyped that subsequently underwent bioinformatic analyses. DNA from validated CHS cases was extracted from frozen blood samples preserved in liquid nitrogen, while DNA from tumor-free controls was extracted from fresh blood. SNP genotyping was conducted by PCR. RESULTS The variant T allele of IGF1R (rs2016347) is potentially correlated with poor outcome in patients with conventional CHS. The GT and TT genotypes of IGF1R rs2016347 predicted statistically significant higher risk of tumor metastasis and higher histological grade of CHS. CONCLUSIONS We hypothesized that IGF1 member polymorphisms are associated with chondrosarcoma. We found that genetic polymorphisms in IGF1 pathway members are associated with elevated risk and poor prognosis of conventional CHS patients in Chinese populations. IGF1R rs2016347 polymorphisms were associated with the risk of lung metastasis of CHS. The IGF1 pathway members do not appear to be involved in the tumorigenesis of CHS.
胰岛素样生长因子 1（IGF1）途径深度参与细胞增殖，包括肿瘤发生。在某些恶性肿瘤中，包括软骨肉瘤（CHS），揭示了 IGF1 途径成员的异常遗传改变。我们提出，IGF1 途径中的遗传多态性可能与中国人群中 CHS 的肿瘤发生易感性和预后相关。
本研究纳入了 112 例经病理诊断的 CHS 病例和 104 例无癌症对照。IGF1 途径成员有 5 个单核苷酸多态性（IGF1R rs2016347、IGF1 rs1520220、IGF1 rs2946834、IGF3BP3 rs2270628 和 IGF2 rs4320932）进行了基因分型，并随后进行了生物信息学分析。从保存在液氮中的冷冻血液样本中提取经证实的 CHS 病例的 DNA，而无癌症对照的 DNA 则从新鲜血液中提取。通过 PCR 进行 SNP 基因分型。
IGF1R（rs2016347）的变体 T 等位基因与常规 CHS 患者的不良预后可能相关。IGF1R rs2016347 的 GT 和 TT 基因型预测 CHS 的肿瘤转移风险更高，组织学分级更高。
我们假设 IGF1 成员多态性与软骨肉瘤相关。我们发现，IGF1 途径成员的遗传多态性与中国人群中常规 CHS 患者的风险增加和预后不良相关。IGF1R rs2016347 多态性与 CHS 肺转移的风险相关。IGF1 途径成员似乎不参与 CHS 的肿瘤发生。
