A novel strategy based on histological protein profiling in‐silico for identifying potential biomarkers in urinary bladder cancer

Abstract

OBJECTIVE To screen a publicly available immunohistochemistry (IHC) based web‐atlas, to identify key proteins in bladder cancer that might serve as potential biomarkers. MATERIALS AND METHODS The first version of the Human Protein Atlas (HPA 1.0), with 660 proteins, was visually examined to identify proteins with a variable staining pattern among the 12 tissue samples representing bladder cancer. None or limited previous characterization in bladder cancer, as well as a supportive Western blot, were also required. The selected proteins were then evaluated in an independent set of patient samples (106 tumour samples of differing stage and grade) represented in a tissue microarray (TMAi). The IHC expression of the identified proteins in the TMAi was scored and related to tumour stage and grade. RESULTS The expression profiles of the 13 proteins selected from the web‐atlas were confirmed in the TMAi. Expression patterns for seven proteins were significantly altered (P < 0.05) with higher stage and/or grade. Three of those (CN130, DSG3, PHF6) lack characterization in bladder cancer, whereas the remaining four proteins have previously been suggested as key proteins/potential biomarkers in cancer, some of them also in bladder cancer. CONCLUSION New candidate proteins for urinary bladder cancer were identified through screening of the publicly available HPA 1.0. Although further evaluation is necessary, this strategy is promising in the search for new biomarkers, with potential to improve the management of patients with this disease.

Immunohistochemical analysis of chromatin remodeler DAXX in high grade urothelial carcinoma

“…There is only one previous study by Segersten et al [3] on DAXX immunohistochemistry in bladder neoplasms. The investigation was performed on tissue microarray (TMA) material comprising a range of noninvasive and invasive bladder cancer.…”

“…For instance, a third of patients with T1 tumors remain recurrence-free after BCG treatment, while a third die from the disease. Therefore clinical biomarkers identifying aggressive tumors are clearly desirable [3]. …”

“…However, in clinical routine, mainly formalin fixed paraffin-embedded tissue samples have been preserved and archived. To retrieve information at protein level from these invaluable materials, with long and extensive patient follow-up data, immunohistochemistry is an ideal approach to identify potential new biomarkers [3]. …”

CD99 is a novel prognostic stromal marker in non‐small cell lung cancer

“…Haematoxylin–eosin stained slides were reviewed by two pathologists (PM, JB) and tumour areas to be included in the TMA were marked. The TMA was constructed using a manual tissue arrayer (MTA‐1, Beecher Instruments, Sun Prairie, CA), essentially as previously described 26, 27. All tumours were included in duplicates (2 × 1 mm tissue cores).…”

“…The TMA was constructed using a manual tissue arrayer (MTA-1, Beecher Instruments, Sun Prairie, CA), essentially as previously described. 26,27 All tumours were included in duplicates (2 Â 1 mm tissue cores). Clinical and pathological parameters are summarised in Supporting Information independent cohort (Lund cohort), used for validation of clinical associations, consisted of specimens from 240 NSCLC patients from Lund University Hospital, previously described by Saito et al 28 Data on overall survival for this cohort was obtained from the National Population Register.…”