Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
Northern Clinical School, The University of Sydney, Sydney, New South Wales 2065, Australia.
J Proteome Res. 2024 Oct 4;23(10):4523-4537. doi: 10.1021/acs.jproteome.4c00440. Epub 2024 Sep 12.
Clinical and pathological factors are insufficient to accurately identify patients at risk of early recurrence after curative-intent treatment of colorectal liver metastases (CRLM). This study aimed to identify candidate prognostic proteogenomic biomarkers for early intrahepatic recurrence after curative-intent resection of CRLM. Patients diagnosed with intrahepatic recurrence within 6 months of liver resection were categorized as the "early recurrence" group, while those who achieved a recurrence-free status for 10 years were designated as "durable remission". Comprehensive genomic and proteomic profiling of fresh frozen samples from these prognostically distinct groups was performed using the TruSight Oncology 500 assay and label-free data-dependent acquisition liquid chromatography-mass spectrometry. Genetic alterations were identified in 117 of the 523 profiled genes in patients with early recurrence. The most common somatic mutations linked to early recurrence were (88%), (71%), (38%), and (21%). alterations were absent in samples from patients with a durable remission. Calponin-2, versican core protein, glutathione peroxidase 3, fibulin-5, and amyloid-β precursor protein were upregulated more than 2-fold in early recurrence. Exploratory analysis of these proteogenomic biomarkers suggests that , calponin-2, and glutathione peroxidase 3 may have the potential to predict early recurrence, enabling improved prognostication and precision oncology in CRLM.
临床和病理因素不足以准确识别结直肠癌肝转移（CRLM）根治性治疗后早期复发的高危患者。本研究旨在确定用于预测结直肠癌肝转移根治性切除术后早期肝内复发的候选预后蛋白基因组生物标志物。将肝切除术后 6 个月内诊断为肝内复发的患者归类为“早期复发”组，而那些在 10 年内无复发状态的患者则被指定为“持久缓解”组。使用 TruSight Oncology 500 检测和无标记数据依赖型采集液相色谱-质谱法对这些具有不同预后的新鲜冷冻样本进行综合基因组和蛋白质组分析。在早期复发患者的 523 个分析基因中，有 117 个存在基因改变。与早期复发相关的最常见的体细胞突变是 (88%)、 (71%)、 (38%) 和 (21%)。持久缓解组的样本中不存在 改变。在早期复发中，钙调蛋白 2、核心蛋白聚糖、谷胱甘肽过氧化物酶 3、纤维连接蛋白 5 和淀粉样前体蛋白的上调超过 2 倍。对这些蛋白基因组生物标志物的探索性分析表明， 、钙调蛋白 2 和谷胱甘肽过氧化物酶 3 可能具有预测早期复发的潜力，从而改善了结直肠癌肝转移患者的预后预测和精准肿瘤学。
