Pancreatic cancer is among the most lethal malignancies worldwide. We aimed to identify novel prognostic markers by applying mass spectrometry (MS)-based proteomic analysis to formalin-fixed paraffin-embedded (FFPE) tissues. Resectable, node positive pancreatic ductal adenocarcinoma (PDAC) with poor (n 5 4) and better (n 5 4) outcomes, based on survival duration, with essentially the same clinicopathological backgrounds, and noncancerous pancreatic ducts (n 5 5) were analyzed. Cancerous and noncancerous cells collected from FFPE tissue sections by laser microdissection (LMD) were processed for liquid chromatography (LC)-tandem MS (MS/MS). Candidate proteins were identified by semiquantitative comparison and then analyzed quantitatively using selected reaction monitoring (SRM)-based MS. To confirm the associations between candidate proteins and outcomes, we immunohistochemically analyzed a cohort of 87 cases. In result, totally 1,229 proteins were identified and 170 were selected as candidate proteins for SRM-based targeted proteomics. Fourteen proteins overexpressed in cancerous as compared to noncancerous tissue showed different expressions in the poor and better outcome groups. Among these proteins, we found that three novel proteins ECH1, OLFM4 and STML2 were overexpressed in poor group than in better group, and that one known protein GTR1 was expressed reciprocally. Kaplan-Meier analysis showed high expressions of all four proteins to correlate with significantly worse overall survival (p < 0.05). In conclusion, we identified four proteins as candidates of prognostic marker of PDAC. The combination of shotgun proteomics verified by SRM and validated by immunohistochemistry resulted in the prognostic marker discovery that will contribute the understanding of PDAC biology and therapeutic development.
PurposeTo investigate the 2-year outcomes of three monthly intravitreal ranibizumab injections followed by as-needed reinjections to treat polypoidal choroidal vasculopathy (PCV).MethodsSeventy-five consecutive eyes with naïve symptomatic PCV with 2 years of follow-up after treatment were studied prospectively.ResultsThe mean (±SD) numbers of injections were 4.2±1.3 that included three monthly injections in the loading phase and 1.6±1.7 during years 1 and 2, respectively (mean 2-year total, 5.6±1.9). The baseline logarithm of the minimum angle of resolution visual acuity (VA) was 0.59±0.51 that improved significantly (p=0.001 for both comparisons) to 0.37±0.33 and 0.41±0.40 at 1 and 2 years, respectively, after the first injection. Although no significant difference was found between years 1 and 2 after the first injection, the VA tended to decrease slightly during year 2. The improved foveal thickness was maintained during year 2. Thirty (40%) eyes and 19 (25%) eyes, respectively, at years 1 and 2 after the first injection had no polypoidal lesions on indocyanine green angiography. A branching vascular network (BVN) remained in all eyes 2 years after the first injection and tended to increase in size during year 2.ConclusionsThe 2-year outcomes showed significant VA and foveal thickness improvements in eyes with PCV. During year 2, the magnitude of the improvement was lower compared with year 1. An as-needed reinjection schedule might not prevent polypoidal lesions or BVNs from regrowing. Further investigations should establish a treatment strategy for PCV.
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