Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer
Abstract Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median surviva...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10840-3 |
| _version_ | 1797832063656656896 |
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| author | Vaishali Jain Javed Akhtar Ratna Priya Puja Sakhuja Surbhi Goyal Anil Kumar Agarwal Vivek Ghose Ravindra Varma Polisetty Ravi Sirdeshmukh Fouzia Siraj Poonam Gautam |
| author_facet | Vaishali Jain Javed Akhtar Ratna Priya Puja Sakhuja Surbhi Goyal Anil Kumar Agarwal Vivek Ghose Ravindra Varma Polisetty Ravi Sirdeshmukh Fouzia Siraj Poonam Gautam |
| author_sort | Vaishali Jain |
| collection | DOAJ |
| description | Abstract Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified ‘neutrophil degranulation’ and ‘HIF1 activation’ to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC. |
| first_indexed | 2024-04-09T14:02:50Z |
| format | Article |
| id | doaj.art-fd77043516ed424fbe4a2e82f2cf334b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T14:02:50Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-fd77043516ed424fbe4a2e82f2cf334b2023-05-07T11:15:45ZengBMCBMC Cancer1471-24072023-05-0123111510.1186/s12885-023-10840-3Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancerVaishali Jain0Javed Akhtar1Ratna Priya2Puja Sakhuja3Surbhi Goyal4Anil Kumar Agarwal5Vivek Ghose6Ravindra Varma Polisetty7Ravi Sirdeshmukh8Fouzia Siraj9Poonam Gautam10ICMR-National Institute of Pathology, Safdarjung Hospital CampusICMR-National Institute of Pathology, Safdarjung Hospital CampusICMR-National Institute of Pathology, Safdarjung Hospital CampusGovind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER)Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER)Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER)Manipal Academy of Higher Education (MAHE)Department of Biochemistry, Sri Venkateswara College, University of DelhiManipal Academy of Higher Education (MAHE)ICMR-National Institute of Pathology, Safdarjung Hospital CampusICMR-National Institute of Pathology, Safdarjung Hospital CampusAbstract Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified ‘neutrophil degranulation’ and ‘HIF1 activation’ to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC.https://doi.org/10.1186/s12885-023-10840-3Gallbladder carcinomaLymph node metastasisTissue proteomicsiTRAQ |
| spellingShingle | Vaishali Jain Javed Akhtar Ratna Priya Puja Sakhuja Surbhi Goyal Anil Kumar Agarwal Vivek Ghose Ravindra Varma Polisetty Ravi Sirdeshmukh Fouzia Siraj Poonam Gautam Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer BMC Cancer Gallbladder carcinoma Lymph node metastasis Tissue proteomics iTRAQ |
| title | Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer |
| title_full | Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer |
| title_fullStr | Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer |
| title_full_unstemmed | Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer |
| title_short | Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer |
| title_sort | tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer |
| topic | Gallbladder carcinoma Lymph node metastasis Tissue proteomics iTRAQ |
| url | https://doi.org/10.1186/s12885-023-10840-3 |
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