Novel Biomarkers – Amphiregulin (AREG)

Amphiregulin (AREG) is a biologically active growth factor that binds to the epidermal growth factor receptor (EGFR), playing a vital role in cell growth, tissue regeneration, and immune system regulation.

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Amphiregulin (AREG)

Produced by activated immune cells, AREG exists first as a membrane-bound precursor (pro-AREG) and is later released in its soluble form to activate EGFR pathways. Because of its central role in EGFR signalling, Amphiregulin is being explored as a novel biomarker for various cancers, inflammatory conditions, and fibrotic diseases.

AREG is involved in a wide range of biological processes, including:

Tissue Repair and Regeneration: Promotes healing and cell proliferation after injury.

Immune Modulation: Supports type 2 immune responses that help resolve inflammation.

Pubertal Development: Linked to breast development and onset of puberty in females.

Ovarian Function: Stimulates ovulation through luteinising hormone activity.

Although AREG is found in low concentrations in healthy individuals, its levels significantly rise in response to cellular stress, tissue injury, or malignancy.

Other Applications

Ongoing research is evaluating AREG as a diagnostic and prognostic blood biomarker for the following conditions:

  • Cancer diagnosis and staging (breast, ovarian, liver, lung, and colorectal)
  • Fibrotic liver diseases
  • Tissue injury and repair monitoring
  • Hormonal and reproductive health

Biochip Array Technology

Randox biochip technology enables precise measurement of sPD-1, providing valuable insights into immune regulation and disease progression.

Clinical MultiSTAT_Biochip Explained

The Evidence MultiSTAT

Meet the Evidence MultiSTAT

The Evidence MultiSTAT is an easy to use, small footprint analyser facilitating on-site simultaneous detection of multiple biomarkers.

Using chemiluminescence as a measurement principle, the Evidence MultiSTAT consistently delivers accurate results.

With minimal sample preparation required, this versatile benchtop analyser can achieve accurate, quantitative results in minutes.

MultiSTAT Cartridge

Meet the Cartridge

The Evidence MultiSTAT cartridge contains the reagents required for the chemiluminescent reaction to take place incorporated into its wells.

The process from sample entry to results can be completed in 2 simple steps, with minimal risk of human error.

No other components are required.

References

Singh, S. S., Chauhan, S. B., Kumar, A., Kumar, S., Engwerda, C. R., Sundar, S., & Kumar, R. (2022). Amphiregulin in cellular physiology, health, and disease: Potential use as a biomarker and therapeutic target. Journal of Cellular Physiology, 237, 1143–1156.

Zaiss, D. M. W., Gause, W. C., Osborne, L. C., & Artis, D. (2015). Emerging functions of amphiregulin in orchestrating immunity, inflammation and tissue repair. Immunity, 42, 216–226.

Hsu, C. Y., Mutee, A. F., Porras, S., Pineda, I., Mustafa, M. A., Saadh, M. J., Adil, M., & H A, Z. (2024). Amphiregulin in infectious diseases: Role, mechanism, and potential therapeutic targets. Microbial Pathogenesis, 186, 106463.

Peterson, E. A., Shabbeer, S., & Kenny, P. A. (2012). Normal range of serum amphiregulin in healthy adult human females. Clinical Biochemistry, 45, 460–463.

Biro, F. M., Pinney, S. M., Schwartz, R. C., Huang, B., Cattran, A. M., & Haslam, S. Z. (2017). Amphiregulin as a novel serum marker of puberty in girls. Journal of Pediatric and Adolescent Gynecology, 30, 535–539.

Busser, B., Sancey, L., Brambilla, E., Coll, J. L., & Hurbin, A. (2011). The multiple roles of amphiregulin in human cancer. Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, 1816, 119–131.

Kjær, I. M., Olsen, D. A., Brandslund, I., Bechmann, T., Jakobsen, E. H., Bogh, S. B., & Madsen, J. S. (2020). Dysregulated EGFR pathway in serum in early-stage breast cancer patients: A case control study. Scientific Reports, 10, 6714.

LaMarca, H. L., & Rosen, J. M. (2007). Estrogen regulation of mammary gland development and breast cancer: Amphiregulin takes center stage. Breast Cancer Research, 9, 304.

Qi, C. F., Liscia, D. S., Normanno, N., Merlo, G., Johnson, G. R., Gullick, W. J., Ciardiello, F., Saeki, T., Brandt, R., & Kim, N. (1994). Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas. British Journal of Cancer, 69, 903–910.

Peterson, E. A., Pectasides, E., Shabbeer, S., Wiechmann, L., Sparano, J. A., & Kenny, P. A. (2013). Evaluation of serum amphiregulin levels in breast cancer patients and cancer-free controls. Experimental Hematology & Oncology, 2, 25.

Lamber, E. P., Horwitz, A. A., & Parvin, J. D. (2010). BRCA1 represses amphiregulin gene expression. Cancer Research, 70, 996–1005.

Fang, L., Sun, Y. P., & Cheng, J. C. (2023). The role of amphiregulin in ovarian function and disease. Cellular and Molecular Life Sciences, 80, 60.

Carvalho, S., Lindzen, M., Lauriola, M., Shirazi, N., Sinha, S., Abdul-Hai, A., Levanon, K., Korach, J., Barshack, I., Cohen, Y., Onn, A., Mills, G., & Yarden, Y. (2016). An antibody to amphiregulin, an abundant growth factor in patients’ fluids, inhibits ovarian tumors. Oncogene, 35, 438–447.

D’Antonio, A., Losito, S., Pignata, S., Grassi, M., Perrone, F., De Luca, A., Tambaro, R., Bianco, C., Gullick, W. J., Johnson, G. R., Iaffaioli, V. R., Salomon, D. S., & Normanno, N. (2002). Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas. International Journal of Oncology, 21, 941–948.

Awad, A. E., Ebrahim, M. A., Eissa, L. A., & El-Shishtawy, M. M. (2019). Dickkopf-1 and amphiregulin as novel biomarkers and potential targets in hepatocellular carcinoma. International Journal of Hematology-Oncology and Stem Cell Research, 13, 153–163.

Han, S. X., Bai, E., Jin, G. H., He, C. C., Guo, X. J., Wang, L. J., Li, M., Ying, X., & Zhu, Q. (2014). Expression and clinical significance of YAP, TAZ and AREG in hepatocellular carcinoma. Journal of Immunology Research, 2014, 261365.

Addison, C. L., Ding, K., Zhao, H., Le Maître, A., Goss, G. D., Seymour, L., Tsao, M. S., Shepherd, F. A., & Bradbury, P. A. (2010). Plasma transforming growth factor alpha and amphiregulin protein levels in NCIC clinical trials group BR.21. Journal of Clinical Oncology, 28, 5247–5256.

Ishikawa, N., Daigo, Y., Takano, A., Taniwaki, M., Kato, T., Hayama, S., Murakami, H., Takeshima, Y., Inai, K., Nishimura, H., Tsuchiya, E., Kohno, N., & Nakamura, Y. (2005). Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. Cancer Research, 65, 9176–9184.

Chen, H., Qian, J., Werner, S., Cuk, K., Knebel, P., & Brenner, H. (2017). Development and validation of a panel of five proteins as blood biomarkers for early detection of colorectal cancer. Clinical Epidemiology, 9, 517–526.

Chayangsu, C., Khunsri, S., Sriuranpong, V., & Tanasanvimon, S. (2017). The correlations between serum amphiregulin and other clinicopathological factors in colorectal cancer. Journal of Gastrointestinal Oncology, 8, 980–984.

Santamaría, E., Rodríguez-Ortigosa, C. M., Uriarte, I., Latasa, M. U., Urtasun, R., Alvarez-Sola, G., Bárcena-Varela, M., Colyn, L., Arcelus, S., Jiménez, M., Deutschmann, K., Peleteiro-Vigil, A., Gómez-Cambronero, J., Milkiewicz, M., Milkiewicz, P., & Sang, R. (2019). The epidermal growth factor receptor ligand amphiregulin protects from cholestatic liver injury and regulates bile acids synthesis. Hepatology, 69, 163–1647.

Berasain, C., García-Trevijano, E. R., Castillo, J., Erroba, E., Santamaría, M., Lee, D. C., Prieto, J., & Avila, M. A. (2005). Novel role for amphiregulin in protection from liver injury. The Journal of Biological Chemistry, 280, 19012–19020.

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