Evaluating the correlation between human epididymis protein 4 (HE4) serum levels and lymph node involvement and standard uptake value (SUV) in positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC)

Lung cancer ranks first among the causes of cancer-related death in men and women. Five-year survival of lung cancer patients, most of whom are diagnosed at advanced stages, is around 15% in the entire patient population. Anatomical surgical resections, which are the most effective treatment methods, are only possible in cases diagnosed in the early stages. For these reasons, biomarkers that can be used in the diagnosis and follow-up of lung cancer are needed. One of the prominent molecules in the studies on this subject in recent years is the Human Epididymis Protein (HE4). Studies on the usability of HE4, which has been approved by the FDA as a biomarker for the diagnosis, evaluation of the treatment response and monitoring of the disease for ovarian cancers, are ongoing for the diagnosis, treatment response evaluation and follow-up in lung cancers. Studies have shown that serum HE4 levels are significantly higher in patients diagnosed with NSCLC compared to healthy control populations and patients with benign lung pathologies. It is shown that serum HE4 levels increase with the stage of the disease. In this study, data of 60 cases diagnosed with NSCLC between February 2019 and January 2020 in Hacettepe University Faculty of Medicine, Department of General Thoracic Surgery and Department of Oncology, were included. Demographic information of the patients, comorbid diseases, smoking history, CEA levels at the time of diagnosis, histological diagnosis, stage of the disease according to the eighth TNM staging system, SUV, MTV, TLG values and serum HE4 levels at the time of diagnosis were evaluated. According to the eighth TNM staging system, no significant difference was observed between serum HE4 levels of patients at different stages, contrary to the literature (p = 0.232). It was thought that the heterogeneous distribution of the histological diagnosis in the stage groups and the determination of the stage by more than one factor might have caused the results to be incompatible with the literature. Serum HE4 levels of squamous cell carcinoma cases were significantly higher than adenocarcinoma cases. The reason for this result was the low number of live cells in the lepidic pattern and ground-glass lesions frequently encountered in adenocarcinomas, and high glucose flow and cellular metabolism due to excessive expression of glucose transport proteins in SCC. The serum HE4 level of the cases correlated weakly with age (p = 0.022; r = 0.295), cigarette consumption (p = 0.040; r = 0.294) and SUVmax (p = 0.007; r = 0.347). Serum HE4 level was found to be correlated with MTV (p = 0.047 r = 0.400) and TLG value (p = 0.032; r = 0.430) with medium strength. As a result of regression analysis, tumor histology (p = 0.017), patient's age (p = 0.021), SUVmax value (p = 0.017), cigarette consumption amount (p = 0.001) and T stage (p = 0.041) are found to be the factors affecting the serum HE4 levels. It was concluded that the prognostic use of serum HE4 levels in patients with NSCLC would be limited, since no correlation with stage of the disease could be found. On the other hand, it provides information about tumor burden and metabolism due to its higher correlation with metabolic parameters such as SUVmax, MTV, TLG and due to its higher levels in SCC compared to adenocarcinoma and due to the fact that it is affected by the T stage. Serum HE4 levels may play a guiding role in the monitoring of the treatment response and the possibility of relapse disease or the development of secondary primary malignancy. Keywords: Human Epididymis Protein (HE4), Lung Cancer, Positron Emission Tomography (PET), Standard Uptake Value (SUV), Lymph Node.