Eukaryotic translation initiation factor 3 subunit A (eIF3a) is the largest subunit of the eukaryotic translation initiation factor 3 (eIF3). eIF3a plays an integral role in protein biosynthesis, hence impacting the onset, development, and treatment of tumors. The proteins regulated by eIF3a are still being explored in vivo. In this study, a Cre-loxP system was used to generate eIF3a conditional knockout mice. Tandem mass tag (TMT) labeling with LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in fat, lungs, skin, and spleen tissue of the eIF3a knockout mice and controls. Bioinformatics analysis was then used to explore the functions and molecular signaling pathways of these protein landscapes. It was observed that eIF3a is essential for life sustenance. Abnormal tissue pathology was found in the lungs, fat, skin, spleen, and thymus. In total, 588, 210, 324, and 944 DEPs were quantified in the lungs, fat, skin, and spleen, respectively, of the eIF3a knockout mice as compared to the control. The quantified differentially expressed proteins were tissue-specific, except for eight proteins shared by the four tissues. A broad range of functions for eIF3a, including cellular signaling pathway, immune response, metabolism, defense response, phagocytes, and DNA replication, has been revealed using bioinformatics analysis. Herein, several pathways related to oxidative stress in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, including nitrogen metabolism, peroxisome, cytochrome P450 drug metabolism, pyruvate metabolism, PPAR signaling pathway, phospholipase D signaling pathway, B-cell receptor signaling pathway, ferroptosis, and focal adhesion, have been identified. Collectively, this study shows that eIF3a is an essential gene for sustaining life, and its downstream proteins are involved in diverse novel functions beyond mRNA translational regulation.

UNASSIGNED: Hypodensity of pancreatic ductal adenocarcinoma (PDAC) during contrast-enhanced computed tomography (CECT) examination is common, but a minority of PDAC patients exhibit hyperdense images. The present study examined the clinical characteristics and protein landscape of PDAC with hyperdensity.
UNASSIGNED: A total of 844 pathologically confirmed PDAC patients who underwent CECT before surgery were included. During the parenchymal phase of CECT, patients were assigned to the hyperdense or hypodense group based on CT values. Clinical and CT characteristics for predicting relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. The expression of the tumor angiogenesis marker CD31 and stroma-related protein CTHRC1 were analyzed using immunohistochemistry (IHC) assay to evaluate differences between the two groups. Proteomics was performed to compare the possible mechanisms underlying the differential enhancement on CT scans.
UNASSIGNED: Based on CECT, 43 and 801 PDAC patients had hyperdense and hypodense lesions, respectively. All 43 patients presented a hyperdense lesion in the parenchymal phase. The mean CECT values of the hyperdense group were higher than the hypodense group (102.5 ± 17.4 and 53.7 ± 18.7, respectively, P < 0.001). The hyperdense group had a better prognosis than the hypodense group (median RFS, 19.97 vs. 12.34 months, P = 0.0176; median OS, 33.6 vs. 20.3 months, P = 0.047). Multivariate analysis showed that age, higher CA19-9 levels (> 300 U/ml), tumor stage, tumor differentiation, tumor CT density, and adjuvant chemotherapy were significant independent prognostic factors for OS. CD31 immunohistochemical staining showed that the hyperdense PDACs had a higher microvessel density than the hypodense group (P < 0.001). CTHRC1 expression was higher in the hypodense group (P = 0.019). Sixty-eight differentially expressed proteins were found using the tandem mass tag labeling-based quantification of the proteomes of PDAC tissue samples, and 7 proteins (POFUT1, PKP2, P0DOX4, ITPR1, HBG2, IGLC3, SAA2) were related to angiogenesis.
UNASSIGNED: Patients who presented with a hyperdense mass on CECT had a higher microvessel density and better prognosis. Anti-angiogenic therapy may be suitable for these patients.