Revision of the significance of serological tumor-associated markers for lung adenocarcinoma taking into account HE-4

Human epididymis protein 4 (HE-4), traditionally used together with CA125 as a serum tumor-associated marker (TAM) of ovarian cancer, is now considered a promising diagnostic biomarker for lung cancer. the aim of the study was to compare the diagnostic characteristics of HE-4 and traditional OM in lung adenocarcinoma patients.

Material and Methods. The serum levels of HE-4, CEA, SCCA, Cyfra 21–1, ProGRP, CA125 and CA 15–3 were analyzed in the serum of 77 patients with morphologically confirmed lung adenocarcinoma and 34 patients with non-malignant lung diseases (NLD) using a CL-1200i automatic analyzer (Mindray, China). The reference values of the markers (upper limit of 95 % confidence interval in healthy donors) were provided by manufacturer. Age-dependent cutoffs were used for HE-4.

Results. In the general group of lung adenocarcinoma patients, the medians of HE-4, CEA, Cyfra 21–1, CA125, and CA15–3 levels significantly exceeded the corresponding values in the NLD group, but only for HE-4 the median did exceed the cutoff. The highest proportion of cases exceeding the cutoffs in the lung adenocarcinoma patients was observed for HE-4 (61.0 %), Cyfra 21–1 (41.6 %), and CEA (36.4 %). HE-4, CEA, Cyfra 21–1 and CA125 medians depended on the disease stage and increased with the raise of the local tumor spread and the extent of lymph node involvement. The incidence of elevated levels of at least one marker from the HE-4 + CEA pair in lung adenocarcinoma was 71.4 %, in the HE-4 + Cyfra 21-1 pair – 66.2 %, in the CEA and Cyfra 21–1 pair – 57.1 %, and in the HE-4 + CEA + Cyfra 21–1 combination – 75.3 % (at stage I – 50.0 %; at stage II – 72.7 %; at stage III – 88.5 %; at stage IV – 100 %). The majority of marker-negative cases, in which none of the studied TAMs was elevated, belonged to stage I of the disease (13/17, 76.5 %), three cases to stage II (17.6 %), one case to stage III; not a single marker-negative case was detected at stage IV.

Conclusion. HE-4 has the best diagnostic characteristics in the panel of seven studied TAMs. Assessment of the levels of three TAMs, namely HE-4, CEA and Cyfra 21–1, at the start of treatment in lung adenocarcinoma patients allows for the selection of markers for subsequent monitoring in most patients with stages II–IV and in approximately half of those with stage I.

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