Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer
Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/86209 |
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| author | Dingyu Rao Hua Lu Xiongwei Wang Zhonghong Lai Jiali Zhang Zhixian Tang |
| author_facet | Dingyu Rao Hua Lu Xiongwei Wang Zhonghong Lai Jiali Zhang Zhixian Tang |
| author_sort | Dingyu Rao |
| collection | DOAJ |
| description | Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development. |
| first_indexed | 2024-03-08T21:45:34Z |
| format | Article |
| id | doaj.art-fdf134f242a54f83a1e0d5cc81fb7d43 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T21:45:34Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | eLife |
| spelling | doaj.art-fdf134f242a54f83a1e0d5cc81fb7d432023-12-20T10:15:24ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.86209Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancerDingyu Rao0https://orcid.org/0000-0002-2182-2682Hua Lu1https://orcid.org/0009-0005-7776-0766Xiongwei Wang2Zhonghong Lai3Jiali Zhang4Zhixian Tang5Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaThe First Clinical School of Medicine of Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Longhua District Central Hospital, Shenzhen, ChinaDepartment of Traumatology, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaThe First School of Clinical Medicine, Gannan Medical University, Ganzhou, ChinaDepartment of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaEsophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development.https://elifesciences.org/articles/86209esophageal cancerexosomesCD54diagnosisbiomarkers |
| spellingShingle | Dingyu Rao Hua Lu Xiongwei Wang Zhonghong Lai Jiali Zhang Zhixian Tang Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer eLife esophageal cancer exosomes CD54 diagnosis biomarkers |
| title | Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer |
| title_full | Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer |
| title_fullStr | Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer |
| title_full_unstemmed | Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer |
| title_short | Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer |
| title_sort | tissue derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer |
| topic | esophageal cancer exosomes CD54 diagnosis biomarkers |
| url | https://elifesciences.org/articles/86209 |
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