Candidate Serological Biomarkers for Cancer Identified from the Secretomes of 23 Cancer Cell Lines and the Human Protein Atlas
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 gr...
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| Published in | Molecular & cellular proteomics Vol. 9; no. 6; pp. 1100 - 1117 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.06.2010
The American Society for Biochemistry and Molecular Biology |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Author | Chang, Kai-Ping Chang, Yu-Sun Wu, Chih-Ching Hsu, Chia-Wei Su, Wen-Hui Liu, Hao-Ping Yu, Jau-Song Yu, Chia-Jung Tai, Dar-In Chen, Chi-De |
| Author_xml | – sequence: 1 givenname: Chih-Ching surname: Wu fullname: Wu, Chih-Ching organization: Molecular Medicine Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 2 givenname: Chia-Wei surname: Hsu fullname: Hsu, Chia-Wei organization: Graduate Institute of Biomedical Sciences, and Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 3 givenname: Chi-De surname: Chen fullname: Chen, Chi-De organization: Graduate Institute of Biomedical Sciences, and Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 4 givenname: Chia-Jung surname: Yu fullname: Yu, Chia-Jung organization: Molecular Medicine Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 5 givenname: Kai-Ping surname: Chang fullname: Chang, Kai-Ping organization: Departments of Otolaryngology-Head and Neck Surgery and Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 6 givenname: Dar-In surname: Tai fullname: Tai, Dar-In organization: Departments of Hepatogastroenterology, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 7 givenname: Hao-Ping surname: Liu fullname: Liu, Hao-Ping organization: Molecular Medicine Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 8 givenname: Wen-Hui surname: Su fullname: Su, Wen-Hui organization: Molecular Medicine Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 9 givenname: Yu-Sun surname: Chang fullname: Chang, Yu-Sun organization: Molecular Medicine Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan – sequence: 10 givenname: Jau-Song surname: Yu fullname: Yu, Jau-Song email: yusong@mail.cgu.edu.tw organization: Molecular Medicine Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20124221$$D View this record in MEDLINE/PubMed |
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| Publisher | Elsevier Inc The American Society for Biochemistry and Molecular Biology |
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| SubjectTerms | Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor - blood Cathepsins - blood Cell Differentiation Cell Line, Tumor Chemokine CXCL12 - blood Cluster Analysis Cytokines - blood Electrophoresis, Polyacrylamide Gel Female Humans Lipopolysaccharide Receptors - blood Male Middle Aged Monocytes - cytology Neoplasm Proteins - blood Neoplasm Proteins - metabolism Neoplasms - blood Neoplasms - metabolism Proteomics Reproducibility of Results Signal Transduction Ubiquitins - blood Young Adult |
| Title | Candidate Serological Biomarkers for Cancer Identified from the Secretomes of 23 Cancer Cell Lines and the Human Protein Atlas |
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