Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland.
Department of Systems Biology and Engineering, Silesian University of Technology, 44-100 Gliwice, Poland.
Cells. 2023 Nov 28;12(23):2721. doi: 10.3390/cells12232721.
Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the and genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that rs11730582 CC carriers had a significantly increased risk of death ( = 0.029), while the rs187116 A allele correlated with a reduced risk of locoregional recurrence ( = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients ( = 0.016). Furthermore, the rs1126772 G variant alone ( = 0.018) and in combination with rs11730582 CC ( = 7 × 10) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that and germline variants may predict treatment effects in NSCLC.
骨桥蛋白 (OPN)-CD44 信号在促进肿瘤进展和转移中发挥重要作用。在癌症中，OPN 和 CD44 的过度表达是侵袭性疾病和不良预后的标志物，与治疗耐药性相关。在这项研究中，我们旨在评估 和 基因中的单核苷酸多态性 (SNP) 与 307 例接受放疗或放化疗的非小细胞肺癌 (NSCLC) 患者临床结局的相关性。还研究了变体对血浆 OPN 水平的潜在影响。多变量分析显示，rs11730582 CC 携带者的死亡风险显著增加 ( = 0.029)，而 rs187116 A 等位基因与根治性治疗亚组局部区域复发风险降低相关 ( = 0.016)。rs11730582/rs187116 组合与这些患者的转移风险升高相关 ( = 0.016)。此外，仅 rs1126772 G 变体 ( = 0.018) 和与 rs11730582 CC 联合 ( = 7×10) 与鳞状细胞癌亚组的总生存期 (OS) 不良相关。rs11730582 CC、rs187116 GG 以及 rs1126772 G 及其各自的组合是不良治疗结局的独立危险因素。还观察到 rs11730582-rs1126772 单倍型对 OS 的影响。这些数据表明， 和 种系变体可能预测 NSCLC 的治疗效果。
