贫血与铁代谢在结直肠癌中的意义

The Role of Anemia and Iron Metabolism in Colorectal Cancer

摘要: 贫血是结直肠癌(CRC)最常见的伴随问题之一，可由肿瘤慢性失血导致的缺铁性贫血(IDA)、炎症驱动的癌相关贫血(CRA/ACD)及二者叠加所致。目前国际上的队列研究提示，CRC患者术前贫血比例可达约40%左右，且不同红细胞指数(如小细胞/正细胞)对应的病因谱、炎症负荷与肿瘤部位存在差异；其中正细胞性贫血更常与系统炎症与不良预后相关。铁代谢异常并非是一种“被动结果”，而是肿瘤与宿主免疫与炎症互作的核心环节：以铁调素(Hepcidin)-铁输出蛋白(FPN)轴为枢纽的铁隔离反应限制循环可用铁，导致功能性缺铁与贫血；同时，肿瘤上皮细胞通过上调铁摄取、抑制铁外排，甚至在局部表达铁调素等方式完成“铁重编程”，以维持核苷酸池和增殖需求，促进肿瘤发生发展。此外，铁稳态与缺氧、氧化应激、肠道微生态及免疫治疗反应密切交织：口服铁可能增加肠腔铁供给但是会改变黏膜、肿瘤相关菌群谱，提示静脉铁在围手术期纠正贫血时或具有“更少微生态扰动”的潜在优势。本文将系统梳理CRC贫血的分型诊断框架、铁代谢与肿瘤免疫微环境的机制联系，并结合患者血液管理(PBM)理念总结围手术期与新辅助治疗或系统治疗背景下的实践要点与未来方向。

Abstract: Anemia is one of the most common comorbid conditions in colorectal cancer (CRC). It may result from iron deficiency anemia (IDA) caused by chronic tumor-related blood loss, cancer-related anemia/anemia of chronic disease (CRA/ACD) driven by inflammation, or an overlap of both conditions. Current international cohort studies suggest that the prevalence of preoperative anemia in patients with CRC is approximately 40%. Different erythrocyte indices, such as microcytic and normocytic patterns, are associated with distinct etiologic profiles, inflammatory burdens, and tumor locations; among these, normocytic anemia is more often associated with systemic inflammation and poor prognosis. Disordered iron metabolism is not merely a “passive consequence”, but rather a central component of the interaction among tumors, host immunity, and inflammation. The hepcidin-ferroportin (FPN) axis serves as the key regulator of iron sequestration, restricting circulating bioavailable iron and thereby leading to functional iron deficiency and anemia. Meanwhile, tumor epithelial cells undergo “iron reprogramming” by upregulating iron uptake, suppressing iron efflux, and even locally expressing hepcidin, thus sustaining nucleotide pools and proliferative demands and promoting tumor initiation and progression. In addition, iron homeostasis is closely intertwined with hypoxia, oxidative stress, the gut microbiota, and responses to immunotherapy. Oral iron supplementation may increase luminal iron availability, but it can also alter mucosal and tumor-associated microbial communities, suggesting that intravenous iron may have the potential advantage of causing less microbiota disturbance when used to correct perioperative anemia. This review systematically summarizes the diagnostic framework for anemia subtypes in CRC, the mechanistic links between iron metabolism and the tumor immune microenvironment, and, within the concept of patient blood management (PBM), the practical considerations and future directions in perioperative care as well as in neoadjuvant or systemic treatment settings.