Gene Expression Patterns Distinguish Mortality Risk in Patients with Postsurgical Shock
JOURNAL OF CLINICAL MEDICINE
Authors: Martinez-Paz, Pedro; Aragon-Camino, Marta; Gomez-Sanchez, Esther; Lorenzo-Lopez, Mario; Gomez-Pesquera, Estefania; Lopez-Herrero, Rocio; Sanchez-Quiros, Belen; de la Varga, Olga; Tamayo-Velasco, Alvaro; Ortega-Loubon, Christian; Garcia-Moran, Emilio; Gonzalo-Benito, Hugo; Heredia-Rodriguez, Maria; Tamayo, Eduardo
Abstract
Nowadays, mortality rates in intensive care units are the highest of all hospital units. However, there is not a reliable prognostic system to predict the likelihood of death in patients with postsurgical shock. Thus, the aim of the present work is to obtain a gene expression signature to distinguish the low and high risk of death in postsurgical shock patients. In this sense, mRNA levels were evaluated by microarray on a discovery cohort to select the most differentially expressed genes between surviving and non-surviving groups 30 days after the operation. Selected genes were evaluated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort to validate the reliability of data. A receiver-operating characteristic analysis with the area under the curve was performed to quantify the sensitivity and specificity for gene expression levels, which were compared with predictions by established risk scales, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA). IL1R2, CD177, RETN, and OLFM4 genes were upregulated in the non-surviving group of the discovery cohort, and their predictive power was confirmed in the validation cohort. This work offers new biomarkers based on transcriptional patterns to classify the postsurgical shock patients according to low and high risk of death. The results present more accuracy than other mortality risk scores.
Quantitative Proteomic Analysis Identifies AHNAK (Neuroblast Differentiation-associated Protein AHNAK) as a Novel Candidate Biomarker for Bladder Urothelial Carcinoma Diagnosis by Liquid-based Cytology
MOLECULAR & CELLULAR PROTEOMICS
Authors: Lee, Hyebin; Kim, Kwangsoo; Woo, Jongmin; Park, Joonho; Kim, Hyeyoon; Lee, Kyung Eun; Kim, Hyeyeon; Kim, Youngsoo; Moon, Kyung Chul; Kim, Ji Young; Park, In Ae; Shim, Bo Bae; Moon, Ji Hye; Han, Dohyun; Ryu, Han Suk
Abstract
Cytological examination of urine is the most widely used noninvasive pathologic screen for bladder urothelial carcinoma (BLCA); however, inadequate diagnostic accuracy remains a major challenge. We performed mass spectrometry-based proteomic analysis of urine samples of ten patients with BLCA and ten paired patients with benign urothelial lesion (BUL) to identify ancillary proteomic markers for use in liquid-based cytology (LBC). A total of 4,839 proteins were identified and 112 proteins were confirmed as expressed at significantly different levels between the two groups. We also performed an independent proteomic profiling of tumor tissue samples where we identified 7,916 proteins of which 758 were differentially expressed. Cross-platform comparisons of these data with comparative mRNA expression profiles from The Cancer Genome Atlas identified four putative candidate proteins, AHNAK, EPPK1, MYH14 and OLFM4. To determine their immunocytochemical expression levels in LBC, we examined protein expression data from The Human Protein Atlas and in-house FFPE samples. We further investigated the expression of the four candidate proteins in urine cytology samples from two independent validation cohorts. These analyses revealed AHNAK as a unique intracellular protein differing in immunohistochemical expression and subcellular localization between tumor and non-tumor cells. In conclusion, this study identified a new biomarker, AHNAK, applicable to discrimination between BLCA and BUL by LBC. To our knowledge, the present study provides the first identification of a clinical biomarker for LBC based on in-depth proteomics.