Although
cancer cell secretome profiling is a promising strategy used to identify potential body fluid-accessible
cancer biomarkers, questions remain regarding the depth to which the
cancer cell secretome can be mined and the efficiency with which researchers can select useful candidates from the growing list of identified
proteins. Therefore, we analyzed the secretomes of 23 human
cancer cell lines derived from 11
cancer types using one-dimensional SDS-PAGE and nano-LC-MS/MS performed on an LTQ-Orbitrap mass spectrometer to generate a more comprehensive
cancer cell secretome. A total of 31,180
proteins was detected, accounting for 4,584 non-redundant
proteins, with an average of 1,300
proteins identified per cell line. Using
protein secretion-predictive algorithms, 55.8% of the
proteins appeared to be released or shed from cells. The identified
proteins were selected as potential marker candidates according to three strategies: (i)
proteins apparently secreted by one
cancer type but not by others (
cancer type-specific marker candidates), (ii)
proteins released by most
cancer cell lines (pan-
cancer marker candidates), and (iii)
proteins putatively linked to
cancer-relevant pathways. We then examined
protein expression profiles in the Human
Protein Atlas to identify
biomarker candidates that were simultaneously detected in the secretomes and highly expressed in
cancer tissues. This analysis yielded 6-137 marker candidates selective for each
tumor type and 94 potential pan-
cancer markers. Among these, we selectively validated monocyte
differentiation antigen CD14 (for
liver cancer),
stromal cell-derived factor 1 (for
lung cancer), and
cathepsin L1 and
interferon-induced 17-kDa
protein (for
nasopharyngeal carcinoma) as potential serological
cancer markers. In summary, the
proteins identified from the secretomes of 23
cancer cell lines and the Human
Protein Atlas represent a focused reservoir of potential
cancer biomarkers.