NAD(P)‐dependent steroid dehydrogenase‐like protein and neutral cholesterol ester hydrolase 1 serve as novel markers for early detection of gastric cancer identified using quantitative proteomics

Abstract

Background Gastric cancer (GC) is the third most common cause of cancer deaths worldwide. In the present study, we aimed to identify novel GC biomarkers by integrating isobaric tags of relative and absolute quantitation (iTRAQ) for aberrantly expressed proteins in GC patients. Methods Using stable isotope tags, we labeled an initial discovery group comprising four paired gastric cancer and adjacent gastric tissue samples, and subjected them to LC‐ESI‐MS/MS. We used a validation set comprising 129 paired gastric cancer and adjacent gastric tissues from patients and benign healthy controls to validate the candidate targets. Results We identified two proteins, NAD(P)‐dependent steroid dehydrogenase‐like (NSDHL) and neutral cholesterol ester hydrolase 1 (NCEH1), that were significantly overexpressed in GC tissues. The sensitivity and specificity of NSDHL were 80.6% and 74.4%, respectively, in GC compared with a sensitivity of 25.6% in adjacent tissues and 24% in benign healthy controls. The area under the ROC curve (AUC) for NSDHL was 0.810 for GC detection. Overexpression of NSDHL in GC was significantly correlated with local tumor invasion. The sensitivity and specificity of NCEH1 were 77.5% and 73.6%, respectively, in GC compared with a sensitivity of 26.4% in adjacent tissues and 20% in benign controls. The AUC for NSDHL was 0.792. Overexpression of NCEH1 was significantly associated with tumor histological classification and local invasion. Moreover, a combined analysis of NSDHL and NCEH1 achieved a sensitivity and specificity of 85.7% and 83%, respectively, and the AUC was 0.872. The combined analysis of NSDHL and NCEH1 was significantly correlated with histological grade and TNM Ⅱ‐Ⅳ staging. Conclusions iTRAQ‐labeled quantitative proteomics represents a powerful method to identify novel cancer biomarkers. The present study identified NSDHL and NCEH1 as useful biomarkers for screening, diagnosis, and prognosis of patients with gastric cancer.

Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context

“…Thus, the associations between functioning, at least, three quarters of the cholesterol synthesis enzymes and solid cancers progression were found [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. Not only overexpression and post-translational activation of enzymes correlated with pathogenic abnormalities, but also a decrease in catalytic function due to down-regulation of expression or pharmacological inhibition (SC5D, NSDHL and EBP).…”

Molecular Mechanism of Malignant Transformation of Balb/c-3T3 Cells Induced by Long-Term Exposure to 1800 MHz Radiofrequency Electromagnetic Radiation (RF-EMR)

“…Yoon SH [ 28 ] found that NSDHL knockdown in BT-20 and MDA-MB-231 resulted in a significant decrease in their viability, colony formation, migration, and invasion abilities ( p < 0.05). Xiao Y [ 29 ] found that the over expression of NSDHL in gastric cancer (GC) was significantly correlated with local tumor invasion. Thus, exposure to 1800 MHz RF-EMR promoted cell migration by regulation of NSDHL and Dhcr21.…”

KIAA1363—A Multifunctional Enzyme in Xenobiotic Detoxification and Lipid Ester Hydrolysis

“…KIAA1363 was originally characterized as a membrane-associated serine hydrolase highly upregulated in the invasive melanoma cell line MUM-2B, the breast carcinoma cell line MDA-MB-231, and in the ovarian carcinoma cell lines OVCAR-5 and SKOV-3 [22]. Many associations or Affymetrix GeneChip array studies found elevated KIAA1363 expression and activity in pancreatic cancer [42][43][44], breast cancer [22,45], gastric cancer [46], adrenal cortical carcinoma [47], colorectal cancer [48], and chronic myeloid leukemia [49]. Since KIAA1363 expression was consistently upregulated in invasive tumors, it may represent a biomarker for early diagnosis and a potential target for the treatment of different cancers [22,44,50].…”