1.Muscle Radiation Attenuation in the Erector Spinae and Multifidus Muscles as a Determinant of Survival in Patients with Gastric Cancer
Soomin AN ; Youn-Jung KIM ; Ga Young HAN ; Wankyu EO
Journal of Korean Biological Nursing Science 2022;24(1):17-25
Purpose:
To determine the prognostic role of muscle area and muscle radiation attenuation in the erector spinae (ES) and multifidus (MF) muscles in patients undergoing gastrectomy.
Methods:
Patients with stage I-III gastric cancer undergoing gastrectomy were retrospectively enrolled in this study. Clinicopathologic characteristics were collected and analyzed. Both paraspinal muscle index of ES/MF muscles (PMIEM) and paraspinal muscle radiation attenuation in the same muscles (PMRAEM) were analyzed at the 3rd lumbar level using axial computed tomographic images. Cox regression analysis was applied to estimate overall survival (OS) and diseasefree survival (DFS).
Results:
There was only a weak correlation between PMIEM and PMRAEM (r = 0.28). Multivariate Cox regression revealed that PMRAEM, but not PMIEM, was an important determinant of survival. PMRAEM along with age, tumor-node-metastasis (TNM) stage, perineural invasion, and serum albumin level were significant determinants of both OS and DFS that constituted Model 1. Harrell’s concordance index and integrated area under receiver operating characteristic curve were greater for Model 1 than for Model 2 (consisting of the same covariates as Model 1 except PMRAEM) or Model 3 (consisting of only TNM stage).
Conclusion
PMRAEM, but not PMIEM, was an important determinant of survival. Because there was only a weak correlation between PMIEM and PMRAEM in this study, it was presumed that they were mutually exclusive. Model 1 consisting of age, TNM stage, perineural invasion, serum albumin level, and PMRAEM was greater than nested models (i.e., Model 2 or Model 3) in predicting survival outcomes.
2.Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial
Ju Hee OH ; Dae Won JUN ; Hye Young KIM ; Seung Min LEE ; Eileen L. YOON ; Jungwook HWANG ; Jung Hwan PARK ; Hanbi LEE ; Wankyu KIM ; Hyunsung KIM
Clinical and Molecular Hepatology 2022;28(3):497-509
Background/Aims:
We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD).
Methods:
An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy.
Results:
DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels.
Conclusions
The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.