Does One Size Fit All? Building a Framework for Medical Professionalism
2011; 86 (11): 1407-1414
An Informatics-assisted Label-free Approach for Personalized Tissue Membrane Proteomics: Case Study on Colorectal Cancer
MOLECULAR & CELLULAR PROTEOMICS
2011; 10 (4)
Medical professionalism has gained global attention over the past decade, but there is a paucity of literature on the universal applicability of the dominant professionalism framework developed in the West. This study proposes an institutional approach to build a framework for medical professionalism that incorporates historical and sociocultural contexts.From 2008 to 2009, the authors adopted nominal group technique (NGT) to determine professional competencies valued by 91 critical stakeholders of medical education (divided into 12 discipline-specific groups) at their institution and in their native society, Taiwan. An expert committee subsequently constructed a framework for professionalism which accounted for a literature review and their understanding of the institution's values and historical roots. To confirm that the framework encompassed the attributes nominated by NGT participants, the authors analyzed transcripts of NGT exercises to refine the final document.Each of 12 NGT groups raised 5 to 23 core competencies and determined the most important five competencies by summing participants' ratings of each item. The expert panel reached consensus on a framework that included eight competencies. The framework differs from the Western framework in the centrality of self-integrity, harmonizing personal and professional roles. Text analysis of the NGT transcripts demonstrated that the framework successfully incorporated top-ranked NGT results.This study challenges the universal applicability of the Western framework of medical professionalism and proposes a process to build a professionalism framework that reflects the cultural heritage and the values of local stakeholders.
View details for DOI 10.1097/ACM.0b013e31823059d1
View details for Web of Science ID 000296624900049
View details for PubMedID 21971298
A Tale of Two Cities: Understanding the Differences in Medical Professionalism Between Two Chinese Cultural Contexts
2014; 89 (6): 944-950
Prioritization of cancer marker candidates based on the immunohistochemistry staining images deposited in the human protein atlas.
2013; 8 (11)
We developed a multiplexed label-free quantification strategy, which integrates an efficient gel-assisted digestion protocol, high-performance liquid chromatography tandem MS analysis, and a bioinformatics alignment method to determine personalized proteomic profiles for membrane proteins in human tissues. This strategy provided accurate (6% error) and reproducible (34% relative S.D.) quantification of three independently purified membrane fractions from the same human colorectal cancer (CRC) tissue. Using CRC as a model, we constructed the personalized membrane protein atlas of paired tumor and adjacent normal tissues from 28 patients with different stages of CRC. Without fractionation, this strategy confidently quantified 856 proteins (?2 unique peptides) across different patients, including the first and robust detection (Mascot score: 22,074) of the well-documented CRC marker, carcinoembryonic antigen 5 by a discovery-type proteomics approach. Further validation of a panel of proteins, annexin A4, neutrophils defensin A1, and claudin 3, confirmed differential expression levels and high occurrences (48-70%) in 60 CRC patients. The most significant discovery is the overexpression of stomatin-like 2 (STOML2) for early diagnostic and prognostic potential. Increased expression of STOML2 was associated with decreased CRC-related survival; the mean survival period was 34.77 ± 2.03 months in patients with high STOML2 expression, whereas 53.67 ± 3.46 months was obtained for patients with low STOML2 expression. Further analysis by ELISA verified that plasma concentrations of STOML2 in early-stage CRC patients were elevated as compared with those of healthy individuals (p < 0.001), suggesting that STOML2 may be a noninvasive serological biomarker for early CRC diagnosis. The overall sensitivity of STOML2 for CRC detection was 71%, which increased to 87% when combined with CEA measurements. This study demonstrated a sensitive, label-free strategy for differential analysis of tissue membrane proteome, which may provide a roadmap for the subsequent identification of molecular target candidates of multiple cancer types.
View details for DOI 10.1074/mcp.M110.003087
View details for Web of Science ID 000289067300004
View details for PubMedID 21209152
Cancer marker discovery is an emerging topic in high-throughput quantitative proteomics. However, the omics technology usually generates a long list of marker candidates that requires a labor-intensive filtering process in order to screen for potentially useful markers. Specifically, various parameters, such as the level of overexpression of the marker in the cancer type of interest, which is related to sensitivity, and the specificity of the marker among cancer groups, are the most critical considerations. Protein expression profiling on the basis of immunohistochemistry (IHC) staining images is a technique commonly used during such filtering procedures. To systematically investigate the protein expression in different cancer versus normal tissues and cell types, the Human Protein Atlas is a most comprehensive resource because it includes millions of high-resolution IHC images with expert-curated annotations. To facilitate the filtering of potential biomarker candidates from large-scale omics datasets, in this study we have proposed a scoring approach for quantifying IHC annotation of paired cancerous/normal tissues and cancerous/normal cell types. We have comprehensively calculated the scores of all the 17219 tested antibodies deposited in the Human Protein Atlas based on their accumulated IHC images and obtained 457110 scores covering 20 different types of cancers. Statistical tests demonstrate the ability of the proposed scoring approach to prioritize cancer-specific proteins. Top 100 potential marker candidates were prioritized for the 20 cancer types with statistical significance. In addition, a model study was carried out of 1482 membrane proteins identified from a quantitative comparison of paired cancerous and adjacent normal tissues from patients with colorectal cancer (CRC). The proposed scoring approach demonstrated successful prioritization and identified four CRC markers, including two of the most widely used, namely CEACAM5 and CEACAM6. These results demonstrate the potential of this scoring approach in terms of cancer marker discovery and development. All the calculated scores are available at http://bal.ym.edu.tw/hpa/.
View details for DOI 10.1371/journal.pone.0081079
View details for PubMedID 24303032