Proteins secreted by tumoral cells (cancer secretomes) have been continuously associated with cancer development and progression processes. In this context, secreted proteins contribute to the signaling mechanisms related to tumor growth and spreading and studies on tumor secretomes provide valuable clues on putative tumor biomarkers.Although the in vitro identification of intracellular proteins in cancer secretome studies has usually been associated with contamination derived from cell lysis or fetal bovine serum, accumulated evidence reports on intracellular proteins with moonlighting functions in the extracellular environment. In this study, we performed a systematic reanalysis of public proteomics data regarding different cancer secretomes, aiming to identify intracellular proteins potentially secreted by tumor cells via unconventional secretion pathways. We found a similar repertoire of unconventionally secreted proteins, including the recurrent identification of nuclear proteins secreted by different cancer cells. In addition, in some cancer types, immunohistochemical data were in line with proteomics identifications and suggested that nuclear proteins might relocate from the nucleus to the cytoplasm. Both the presence of nuclear proteins and the likely unconventional secretion of such proteins may comprise biological signatures of malignant transformation in distinct cancer types and may be targeted for further analysis aiming at the prognostic/ therapeutic value of such features.

Progress in understanding the complexity of a devastating disease such as cancer has underscored the need for developing comprehensive panels of molecular markers for early disease detection and precision medicine applications. The present study was conducted to assess whether a cohesive biological context can be assigned to protein markers derived from public data mining, and whether mass spectrometry can be utilized to screen for the co-expression of functionally related biomarkers to be recommended for further exploration in clinical context. Cell cycle arrest/release experiments of MCF7/SKBR3 breast cancer and MCF10 non-tumorigenic cells were used as a surrogate to support the production of proteins relevant to aberrant cell proliferation. Information downloaded from the scientific public domain was queried with bioinformatics tools to generate an initial list of 1038 cancer-associated proteins. Mass spectrometric analysis of cell extracts identified 352 proteins that could be matched to the public list. Differential expression, enrichment, and protein-protein interaction analysis of the proteomic data revealed several functionally-related clusters of relevance to cancer. The results demonstrate that public data derived from independent experiments can be used to inform biological research and support the development of molecular assays for probing the characteristics of a disease.