Tavares Valéria, Lopes Catarina, Macedo-Silva Catarina, Farinha Mónica, Costa João, Vilas-Boas Maria Isabel, Pinelas Sofia, Assis Joana, Dinis-Ribeiro Mário, Pereira Deolinda, Pereira Carina, Medeiros Rui
Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Pathology and Laboratory Medicine Department/Clinical Pathology/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal.
ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313, Porto, Portugal.
J Thromb Thrombolysis. 2025 May 27. doi: 10.1007/s11239-025-03106-1.
Colorectal cancer (CRC) is the second leading cause of malignancy-related death worldwide, representing a significant health concern. Understanding the disease pathogenesis and identifying potential prognostic biomarkers is critical for improving patients' clinical outcomes. Haemostatic components implicated in cancer-associated thrombosis (CAT) seem to favour CRC progression. As such, genetic markers of thrombophilia might be potential prognostic biomarkers among patients with this malignant disease. To offer perspectives, a retrospective cohort study with 204 CRC patients was conducted to investigate the impact of seven germline haemostatic gene determinants on patient prognosis. A sex-stratified analysis was performed as the variants seem to have a distinct influence depending on the patient's sex. Genomic DNA was extracted from FFPE samples enriched in tumour cells. While the polymorphisms CNTN6 rs6764623 (CC/CA vs. AA; adjusted hazard ratio (aHR) = 0.44; 95% confidence interval (CI), 0.20-0.96; P = 0.040), PTGS2 rs20417 (GG vs. CC/CG; aHR = 2.88; 95%CI, 1.10-7.51; P = 0.031) and RGS7 rs2502448 (TT vs. CT/CC; aHR = 2.35; 95%CI, 1.20-4.61; P = 0.013) were associated with the five-year risk of cancer recurrence, ITGB3 rs5918 was a predictor of the risk of death due to all causes, particularly among male patients (TT vs. CT/CC; aHR = 2.05; 95% confidence interval (CI), 1.13-3.72; P = 0.019). While a sex-specific impact of the SNPs was observed, further investigation in larger cohorts, particularly with an increased representation of female patients, is required to confirm these associations. Collectively, these markers could help improve the prognosis assessment of CRC patients towards a more personalised intervention.
结直肠癌（CRC）是全球恶性肿瘤相关死亡的第二大主要原因，是一个重大的健康问题。了解该疾病的发病机制并确定潜在的预后生物标志物对于改善患者的临床结局至关重要。与癌症相关血栓形成（CAT）相关的止血成分似乎有利于CRC进展。因此，血栓形成倾向的遗传标志物可能是这种恶性疾病患者潜在的预后生物标志物。为了提供相关观点，我们对204例CRC患者进行了一项回顾性队列研究，以调查7种种系止血基因决定因素对患者预后的影响。由于这些变异似乎根据患者性别有不同影响，因此进行了性别分层分析。从富含肿瘤细胞的FFPE样本中提取基因组DNA。虽然多态性CNTN6 rs6764623（CC/CA与AA；调整后风险比（aHR）=0.44；95%置信区间（CI），0.20-0.96；P=0.040）、PTGS2 rs20417（GG与CC/CG；aHR=2.88；95%CI，1.10-7.51；P=0.031）和RGS7 rs2502448（TT与CT/CC；aHR=2.35；95%CI，1.20-4.61；P=0.013）与癌症复发的五年风险相关，但ITGB3 rs5918是全因死亡风险的预测指标，特别是在男性患者中（TT与CT/CC；aHR=2.05；95%置信区间（CI），1.13-3.72；P=0.019）。虽然观察到了SNP的性别特异性影响，但需要在更大的队列中进行进一步研究，特别是增加女性患者的比例，以证实这些关联。总体而言，这些标志物有助于改善CRC患者的预后评估，以实现更个性化的干预。
