Formica Vincenzo, Di Grazia Antonio, Bonomo Maria Vittoria, Frascatani Rachele, Mancone Roberto, Monteleone Giovanni
Medical Oncology Unit, Fondazione Policlinico "Tor Vergata", 00133 Rome, Italy.
Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Cancers (Basel). 2024 Nov 27;16(23):3977. doi: 10.3390/cancers16233977.
BACKGROUND & AIM: Hepcidin, a key hormone in iron homeostasis, is synthesized by colorectal cancer (CRC) cells, particularly in the late stages of tumorigenesis. This study aimed to ascertain whether the serum levels of hepcidin could serve as a prognostic biomarker in microsatellite stable (MSS) metastatic CRC (mCRC). Specifically, we assessed the predictive value of baseline serum hepcidin levels for the overall survival (OS) of patients with MSS mCRC receiving first-line treatment with FOLFOX-panitumumab (RAS/BRAF wild-type) or FOLFOX-bevacizumab (RAS or BRAF mutations).
Serum samples were prospectively collected from 35 normal healthy volunteers (normal controls) and 55 patients with MSS mCRC and analyzed for their content of hepcidin by ELISA.
Serum hepcidin levels were significantly greater in patients with mCRC than in the normal controls. In the mCRC group, patients with baseline levels of hepcidin greater than 40 ng/mL had a significantly shorter 1-year OS rate (39%) than those with hepcidin levels lower than 40 ng/mL (80%) [hazard ratio (HR): 2.94; 95% CI: 1.27-6.84; = 0.01]. A multivariate Cox regression analysis showed that the pre-treatment serum hepcidin levels were an independent prognostic factor for OS, not influenced by other well-known prognostic factors (i.e., CEA status, Karnofsky performance score, number of metastatic sites, RAS/BRAF mutations), and this was evident across all major patient subgroups.
Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.
铁调素是铁稳态中的关键激素，由结直肠癌（CRC）细胞合成，尤其在肿瘤发生的晚期。本研究旨在确定铁调素的血清水平是否可作为微卫星稳定（MSS）转移性结直肠癌（mCRC）的预后生物标志物。具体而言，我们评估了基线血清铁调素水平对接受FOLFOX-帕尼单抗（RAS/BRAF野生型）或FOLFOX-贝伐单抗（RAS或BRAF突变）一线治疗的MSS mCRC患者总生存期（OS）的预测价值。
前瞻性收集35名正常健康志愿者（正常对照）和55名MSS mCRC患者的血清样本，采用酶联免疫吸附测定法（ELISA）分析其铁调素含量。
mCRC患者的血清铁调素水平显著高于正常对照。在mCRC组中，基线铁调素水平大于40 ng/mL的患者1年总生存率（39%）显著低于铁调素水平低于40 ng/mL的患者（80%）[风险比（HR）：2.94；95%置信区间（CI）：1.27 - 6.84；P = 0.01]。多因素Cox回归分析显示，治疗前血清铁调素水平是OS的独立预后因素，不受其他已知预后因素（即癌胚抗原状态、卡氏评分、转移部位数量、RAS/BRAF突变）影响，且在所有主要患者亚组中均如此。
我们的数据表明，基线血清铁调素水平是接受标准一线治疗的MSS mCRC患者OS的独立危险因素。需要进一步进行前瞻性和广泛的研究来证实和验证我们的发现。
