High Serum Elafin Prediction of Poor Prognosis of Locoregional Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor known to have locally advanced and metastatic features which cause a dismal prognosis. We sought to determine whether elafin, a non-invasive and secretory small-molecule marker, could be used to predict prognosis in locoregional ESCC patients in human and in vitro studies. In our human study, 119 subjects were identified as having incident and pathologically-proved ESCC with stage I-IIIA tumors from southern Taiwan between 2000 and 2016. We measured their serum elafin levels at baseline and followed them until the date of cancer death or until January 2020, the end of this study. Those with high serum elafin levels were found to have a 1.99-fold risk (95% confidence interval: 1.17-3.38) shorter survival than those who did not. In our in vitro experiments, elevated elafin levels were found to drive ESCC cell proliferation, migration and invasion, while attenuation of elafin level by shRNA abrogated those effects. We concluded that elafin promotes ESCC motility and invasion and leads to a worse clinical prognosis in ESCC patients without distant metastasis.

Overexpression of ATPase Na+/+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma.

This study aims to identify new upregulated genes related to secretory or membranous proteins to help detect esophageal squamous cell carcinoma (ESCC). First, we performed microarray-based screening of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and seventeen human ESCC specimens. Candidate genes were validated by quantitative PCR (qPCR) and immunohistochemical (IHC) staining of ESCC tissues. Among the paired cancer and adjacent normal tissues from 14 ESCC patients, 10 pairs (71.4%) had overexpression of ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) by qPCR (P = 0.0052). ATP1A1 protein expression was re-confirmed by tissue arrays in 243 ESCC tissues and 126 adjacent normal tissues and by ELISA in 78 serum specimens of ESCC patients. ATP1A1 was 12.3 times (adjusted odds ratio=12.3, 95% CI = 7.2-21.0) more likely to be overexpressed in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to tumor stage. Patients with higher serum ATP1A1 levels had a 2.9-fold (95% CI = 1.1-7.4) risk of late-stage disease (stages III-IV vs. I-II). Downregulation of ATP1A1 expression inhibited the migration and invasion ability of ESCC cell lines in vitro. We concluded that the overexpression of ATP1A1 is strongly associated with the presence and severity of ESCC.

Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma.

This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04-2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC.

Plasma decorin predicts the presence of esophageal squamous cell carcinoma.

Using a microarray technique, we found decorin to be underexpressed, but osteopontin (OPN) to be overexpressed, in esophageal squamous cell carcinoma (ESCC). This study aims to examine whether plasma decorin and OPN plus personal substances use (tobacco, alcohol and areca) can serve as suitable clinical markers to predict the presence of ESCC. In total, 570 archived plasma specimens (275 patients and 295 controls) were collected from 2 medical centers in Taiwan between 2000 and 2008. Decorin and OPN protein levels were measured by ELISA. Means and standard deviation of plasma decorin were 5.6 + or - 3.6 ng/ml in case patients, which were significantly lower than those in controls (7.8 + or - 3.1, p < 0.0001). Plasma OPN levels in case patients were not significantly different from controls (p = 0.33). When compared to subjects with the lowest quartile of plasma decorin, those with the highest quartile one had a significantly lower risk to have ESCC (Adjusted OR = 0.03, p < 0.001). Receiver operator characteristic (ROC) analysis was performed for the combination of plasma decorin and 3 substances use (smoke, alcohol and areca) for the patients compared with the controls. The area under the curve was 88.6% and the optimal cut-point of ROC curve (any 3 factors) had 73.5% sensitivity and 90.2% specificity with approximately 82% of corrected classification. Plasma decorin, but not OPN, is a potential clinical marker for the detection of ESCC. When plasma decorin plus the use of the 3 substances are combined, this factor cluster could be used to detect the presence of ESCC.

Neuropeptide Y gene polymorphism and plasma neuropeptide Y level in febrile seizure patients in Taiwan.

Neuropeptide Y (NPY) has been shown to depress the hyperexcitability of neurons. In the present study, we investigated the association between the nucleotide (nt) 5671 C/T polymorphism of the NPY gene and the plasma NPY level in patients with febrile seizures (FS). Fifty-six patients with FS and 55 control subjects were enrolled. Genotype and allele frequencies were compared. The frequencies of genotypes TT, TC and CC for the NPY gene nt 5671 C/T polymorphism were 21.4%, 28.6% and 50.0%, respectively, in patients with FS, and 14.6%, 40.0% and 45.4%, respectively, in control subjects. The frequencies of alleles T and C were 35.7% and 64.3%, respectively, in patients with FS, while those in the control group were 34.5% and 65.5%, respectively. We found no significant relationship between the NPY gene nt 5671 C/T polymorphism and FS. The plasma NPY concentrations of the FS group, the age-matched non-FS group, and subjects aged > 6 years in the non-FS group were 48.23 +/- 32.49, 55.36 +/- 23.12, and 70.10 +/- 60.31 pg/mL, respectively. These results indicate no statistical difference in plasma NPY concentration between FS patients and the non-FS group. However, plasma NPY concentration was found to increase significantly with age.