Recent Insight about HE4 Role in Ovarian Cancer Oncogenesis

Abstract

Currently, ovarian cancer (OC) is a target of intense biomarkers research because of its frequent late diagnosis and poor prognosis. Serum determination of Human epididymis protein 4 (HE4) is a very important early detection test. Most interestingly, HE4 plays a unique role in OC as it has been implicated not only in OC diagnosis but also in the prognosis and recurrence of this lethal neoplasm, actually acting as a clinical biomarker. There are several evidence about the predictive power of HE4 clinically, conversely less has been described concerning its role in OC oncogenesis. Based on these considerations, the main goal of this review is to clarify the role of HE4 in OC proliferation, angiogenesis, metastatization, immune response and also in the development of targeted therapy. Through a deeper understanding of its functions as a key molecule in the oncogenetic processes underlying OC, HE4 could be possibly considered as an essential resource not only for diagnosis but also for prognosis and therapy choice.

PANC-1 Cell Line as an Experimental Model for Characterizing PIVKA-II Production, Distribution, and Molecular Mechanisms Leading to Protein Release in PDAC

“…The overall information deriving from our study underlines the importance, in the field of biomedical research, of identifying preclinical experimental models that are useful both for characterizing specific cellular mechanisms involved in the progression of PDAC and for evaluating the effects of possible targeted therapeutic strategies. It must also be considered that in recent years, tumor markers have not only been used as disease indicators but are often molecules that actively participate in tumor progression [ 50 ].…”

Diagnostic value of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in lung adenocarcinoma

“…Although HE4 expression has been reported upregulated in various tumors, its functional roles have remained largely unknown. HE4 promotes proliferation, angiogenesis, metastatization, immune response in ovarian cancer ( 5 ). In endometrial cancer, HE4 contributes to proliferation, colony formation, and invasion ( 15 ).…”

“…HE4 is secreted extracellularly into the bloodstream and frequently upregulated in many malignancies as a tumor biomarker. HE4 was commonly used in clinic as its unique roles in ovarian cancer, not only for diagnosis, but also for prognosis and recurrence ( 5 ). In lung cancer, serum HE4 can be used as the diagnosis biomarker for lung cancer (LC), particularly for early-stage LC ( 6 ), and correlates with poor prognosis, especially in Asian patients ( 7 ).…”

Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study

“…HE4 is an acidic inhibitory protein that exacerbates ovarian cancer by facilitating early infiltration and metastasis, thereby accelerating the disease’s progression. Elevated expression levels of HE4 may signal poor clinical regression in patients with ovarian cancer, reflecting the disease’s progression and prognosis to a certain extent ( 19 , 23 , 48 , 54 ).…”

“…Moreover, studies have revealed that serum tumor markers, including carbohydrate antigen 153 (CA153), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and human epididymal protein 4 (HE4), are linked to ovarian cancer prognosis. However, the sensitivity and specificity of these singlemarker tests often fall short of ideal standards (18)(19)(20)(21)(22)(23). To enhance tumor reduction rate, minimize perioperative complications, decrease postoperative chemotherapy resistance, and accurately select patients suitable for NACT, this study utilizes dynamic testing of NLR and tumor markers including CA125, CA199, CEA, CA153, and HE4 before and after NACT.…”