Serum HE4 as a diagnostic and prognostic marker for lung cancer

Iwahori, Kota; Suzuki, Hidekazu; Kishi, Yoshiro; Fujii, Yukihiko; Uehara, Rie; Okamoto, Norio; Kobayashi, Masashi; Hirashima, Tomonori; Kawase, Ichiro; Naka, Tetsuji

doi:10.1007/s13277-012-0356-9

Cited by 66 publications

(58 citation statements)

References 22 publications

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“…HE4 expression has been demonstrated in several lung cancer cell lines [9,79]. The highest HE4 tissue expression was detected in adenocarcinomas of the lung compared with small-cell, squamous, and large-cell lung cancers [81,82]. Nagy et al reported that serum HE4 was highly increased in male patients with lung cancers, even prior to asymptotic cases, indicating serum HE4 could be a sensitive marker for early diagnosis of lung cancer [83].…”

Section: Inflammatory Diseasementioning

confidence: 99%

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Duan

et al. 2016

Expert Review of Molecular Diagnostics

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Section: Inflammatory Diseasementioning

confidence: 99%

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Duan

et al. 2016

Expert Review of Molecular Diagnostics

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“…HE4 has been reported to be upregulated in several types of cancers including those of the ovary (16), endometrium (17), lung (18,19), breast (7,15), stomach and pancreas (20). The expression of HE4 in ovarian cancer was initially reported in 1999 (16), and it was subsequently cleared as a new biological marker of ovarian cancer in 2003 (21).…”

Section: Introductionmentioning

confidence: 99%

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

et al. 2014

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Abstract. Available evidence on the proliferation-promoting effect of HE4 remains controversial, and few studies have been carried out on the molecular mechanism of chemoresistance mediated by HE4. The aim of the present study was to investigate the influence of exogenous recombinant HE4 protein on proliferation and resistance to carboplatin in ovarian cancer cells. The human ovarian cancer cell line (SKOV-3) was exposed to recombinant HE4 protein (0-1 µg/ml) for different durations based on the schemes. Cell viability was evaluated by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Markers of apoptosis (Bax and Bcl-2) were assessed by western blotting. Furthermore, Affymetrix microarray analysis was performed to investigate transcriptome profiling. The differential expression of four genes was verified by quantitative real-time PCR. The HE4 protein enhanced cell viability, promoted accumulation of cells in the G2/M phase and attenuated carboplatin-induced apoptosis. HE4 markedly decreased the Bax/Bcl-2 ratio. Candidate genes (387) (236 upregulated and 151 downregulated) were obtained by microarray analysis. Among those upregulated, several Gene Ontology (GO) terms related to cell cycle regulation and proliferation were significantly overrepresented and those within the downregulated dataset included genes involved in several aspects of the DNA damage response such as positive regulation of apoptosis. No information concerning the EGFR-MAPK pathways in a recent report on HE4 was acquired. The mRNA expression of the candidate genes determined by quantitative real-time PCR was significantly correlated with the microarray data. The present study indicates that the HE4 protein plays a promotive role in the proliferation and resistance to carboplatin in ovarian cancer cells, implicating the value of HE4 to predict tumor growth potential and resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC).

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“…Iwahori et al (17) found elevated levels of serum HE4 not only in SCLC patients (88.9%, 8/9 patients) but also in NSCLC patients (90.0%, 36/40 patients). One significant study examined SCC and AC patients separately and found that HE4 serum levels were 125.05±89.06 and 357.04±220.40 pmol/l, respectively (18).…”

Section: Discussionmentioning

confidence: 97%

Human epididymis protein 4 may not be a reliable screening biomarker for detecting lung carcinoma patients

Çelik

Bulut

2017

Biomedical Reports

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Abstract. Human epididymis protein 4 (HE4) acts as a protease inhibitor. It has been detected in the serum of patients with lung cancer patients and its utility for lung cancer screening was found in different studies. Nevertheless, little is known regarding the expression of HE4 in lung carcinoma subtypes. The aim of the present study was to investigate whether HE4 expression is a reliable marker for detecting any lung carcinoma subtypes, including small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and adenocarcinoma (AC). In total, 141 lung carcinoma patients were enrolled in the study. Biopsy samples were obtained from bronchoscopic biopsy. The tumors were classified as SCLC (group 1, 54 cases) or NSCLC (group 2, 87 cases) based on histology and immunohistochemistry. The latter was sub-grouped as adenocarcinoma (group 2a, AC) and squamous cell carcinoma (group 2b, SCC). The immunohistochemical expression of HE4 was compared between the groups. The study revealed that the majority of the SCLC and SCC cases were devoid of HE4 (90.1 and 89.65%, respectively). Approximately 10% of cases had HE4 immune expression and the staining was focal and moderate throughout the tumor tissue. On the other hand, 78.8% of AC expressed HE4 and the staining was diffuse and strong. The overall HE4 expression in the lung cancer patients was 33.7%. In conclusion, the results of the present study have shown that HE4 is expressed in adenocarcinoma of the lung but it is not frequent in SCC and SCLC. The value of HE4 as a screening biomarker for lung cancer is limited but its presence exclusively in adenocarcinoma may provide new insight for targeted therapy.

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Serum HE4 as a diagnostic and prognostic marker for lung cancer

Cited by 66 publications

References 22 publications

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

Human epididymis protein 4 may not be a reliable screening biomarker for detecting lung carcinoma patients

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