The Evaluation of Urinary HE4, CEA, ProGRP, CYFRA 21-1 and NSE in the Diagnosis of Lung Cancer.

Urinary proteins are effective tumor biomarkers. Human epididymis protein 4 (HE4), progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), cytokeratin-19 fragment 21-1(CYFRA 21-1), and neuron-specific enolase (NSE) in serum, were proposed as tumor biomarkers of lung cancer. Our aim was to identify the urine protein biomarkers that can distinguish patients with lung cancer from healthy individuals and/or patients with benign lung disease with a high level of sensitivity and specificity. These urinary protein concentrations were determined from 212 patients with lung cancer, 80 patients with benign pulmonary conditions, and 100 healthy individuals. In the lung cancer group, urine HE4 median concentration was approximately ten times that in the healthy and/or pulmonary benign disease group; urine CEA, CYFRA21-1, and NSE median concentrations were about eight times, twice, and half as those in the healthy group, respectively. However, the median concentrations of urine ProGRP were almost the same in the healthy, lung benign, and cancer groups. Urine HE4 showed better specificity (94.0% vs 86.0%) and sensibility (72.38% vs 60.65%) than CEA in discriminating patients with lung cancer from healthy controls. A significantly higher ROC area was also obtained with urine HE4 than with CEA (0.87 vs 0.76). Urine HE4 showed the best diagnostic performance, followed by CEA. The levels of urine HE4 and CEA increased significantly in patients with lung cancer, which had little relationship with pathological type and metastasis.

Zhang L ，Zhuang J ，Pang Y ，Song Y ，Li X ，Liu K ，Li S ，Sun T ... -  《-》

Human epididymis protein 4, a novel potential biomarker for diagnostic and prognosis monitoring of lung cancer.

This study aimed to explore the application value of human epididymis protein 4 (HE4) in diagnosing and monitoring the prognosis of lung cancer. First, TCGA (The Cancer Genome Atlas) databases were used to analyze whey-acidic-protein 4-disulfide bond core domain 2 (WFDC2) gene expression levels in lung cancer tissues. Then, a total of 160 individuals were enrolled, categorized into three groups: the lung cancer group (n = 80), the benign lesions group (n = 40), and the healthy controls group (n = 40). Serum HE4 levels and other biomarkers were quantified using an electro-chemiluminescent immunoassay. Additionally, the expression of HE4 in tissues was analyzed through immunohistochemistry (IHC). In vitro cultures of human airway epithelial (human bronchial epithelial [HBE]) cells and various lung cancer cell lines (SPC/PC9/A594/H520) were utilized to detect HE4 levels via western blot (WB). Analysis of the TCGA and UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal) databases showed that WFDC2 gene expression levels were upregulated in lung cancer tissues (p < 0.01). Compared with the control group and the benign group, HE4 was significantly higher in the serum of patients with lung cancer (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed that HE4 had better diagnostic efficacy than classical markers in the differential diagnosis of lung cancer and benign lesions and had the highest diagnostic value in lung adenocarcinoma (area under the ROC curve [AUC] = 0.826). HE4 increased in early lung cancer and positively correlated with poor prognosis (p < 0.001). Moreover, the results of WB and IHC revealed that the expression of HE4 was increased in lung cancer cells (SPC/A549/H520) and lung cancer tissues but decreased in PC9 cells with a lack of exon EGFR19 (p < 0.05). Serum HE4 emerges as a promising novel biomarker for the diagnosis and prognosis assessment of lung cancer.

Zhang T ，Chu L ，Tan W ，Ye C ，Dong H ... -  《-》

Lung Cancer Biomarkers Associated with Increased Peripheral Arterial Stiffness in Middle-aged Chinese Adults.

Li Y ，Gu JW ，Li JX ，Chen FY ，Zhang XQ ，Liu JH ... -  《-》

Establishment of tumor marker reference intervals for different age and gender groups in the healthy population of South China.

Meng Y ，Li X ，Li H ，Gu B ... -  《-》

Potential for trans-pulmonary tumor markers in the early diagnosis of lung cancer: a case report.

Monahan K ，Kammer M ，Su YR ，Iams W ，Grogan E ，Maldonado F ... -  《BMC Pulmonary Medicine》