HAMP, also known as hepcidin antimicrobial peptide, encodes a small peptide hormone that plays a vital role in regulating systemic iron homeostasis. Hepcidin binds to ferroportin, an iron exporter, leading to its internalization and degradation, thus controlling cellular iron efflux and completing an iron-regulating homeostatic loop [4,6]. This regulation is crucial for maintaining normal iron levels in the body, and disruptions can lead to various iron-related disorders.

In disease research, HAMP shows promise as a biomarker. In gastric cancer, high HAMP expression was associated with poor overall survival and was related to immune cell infiltration levels, suggesting it could serve as an independent prognostic biomarker through the immune pathway [1]. In non-small cell lung cancer, HAMP promoted cell proliferation, invasion, and migration by activating the NF-κB pathway, with non-coding RNAs regulating its activity [2]. In hepatocellular carcinoma, HAMP had a good ability to diagnose the disease, predict PD-1 treatment sensitivity, and was positively correlated with immune cell infiltration and immune checkpoint expression [3]. In addition, mutations in HAMP were found to cause an atypical form of juvenile hereditary hemochromatosis, which was misdiagnosed as type 1 diabetes initially [5]. Epigenetic changes in HAMP may also be an early marker for type 2 diabetes [7].

In conclusion, HAMP is essential for iron metabolism regulation. Studies using various models, though not specifically KO/CKO mouse models in the provided references, have revealed its significant roles in multiple disease conditions, including cancer and iron-related disorders. Understanding HAMP provides insights into disease mechanisms and potential biomarker-based diagnostic and prognostic strategies.

References:

1. Yang, Jing, Wei, Hui, Liu, Mengxiao, Wang, Yuping, Zhou, Yongning. 2022. Prognostic biomarker HAMP and associates with immune infiltration in gastric cancer. In International immunopharmacology, 108, 108839. doi:10.1016/j.intimp.2022.108839. https://pubmed.ncbi.nlm.nih.gov/35576847/

2. Li, Zhifeng, Liu, Jinglei, Wang, Ping, He, Guanghui, Yang, Liwei. 2024. HAMP predicts a pivotal role in modulating the malignant behaviors of non-small cell lung cancer cells. In Aging, 16, 8524-8540. doi:10.18632/aging.205819. https://pubmed.ncbi.nlm.nih.gov/38787358/

3. Chen, Guoming, Zhang, Cheng, Li, Danyun, Wang, Ning, Feng, Yibin. 2023. HAMP as a Potential Diagnostic, PD-(L)1 Immunotherapy Sensitivity and Prognostic Biomarker in Hepatocellular Carcinoma. In Biomolecules, 13, . doi:10.3390/biom13020360. https://pubmed.ncbi.nlm.nih.gov/36830729/

4. Hentze, Matthias W, Muckenthaler, Martina U, Galy, Bruno, Camaschella, Clara. . Two to tango: regulation of Mammalian iron metabolism. In Cell, 142, 24-38. doi:10.1016/j.cell.2010.06.028. https://pubmed.ncbi.nlm.nih.gov/20603012/

5. Wu, Hui-Xuan, Liu, Jun-Ying, Yan, De-Wen, Zhou, Zhi-Guang, Zhou, Hou-De. 2020. Atypical juvenile hereditary hemochromatosis onset with positive pancreatic islet autoantibodies diabetes caused by novel mutations in HAMP and overall clinical management. In Molecular genetics & genomic medicine, 8, e1522. doi:10.1002/mgg3.1522. https://pubmed.ncbi.nlm.nih.gov/33016646/

6. Nemeth, Elizabeta, Tuttle, Marie S, Powelson, Julie, Ganz, Tomas, Kaplan, Jerry. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. In Science (New York, N.Y.), 306, 2090-3. doi:. https://pubmed.ncbi.nlm.nih.gov/15514116/

7. Ouni, Meriem, Eichelmann, Fabian, Jähnert, Markus, Schulze, Matthias B, Schürmann, Annette. 2023. Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes. In Molecular metabolism, 75, 101774. doi:10.1016/j.molmet.2023.101774. https://pubmed.ncbi.nlm.nih.gov/37429525/