Proteomic Analysis of Primary Colon Cancer and Synchronous Solitary Liver Metastasis

Kim, Min Jung; Song, Min-Jeong; Jung, YunJae; Lee, Won Suk; Jang, Ho Hee

doi:10.21873/cgp.20161

Cited by 32 publications

(37 citation statements)

References 40 publications

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“…Many patients subsequently develop metastases soon after diagnosis which drastically impacts their prognosis. [ 6 ] Patients without metastasis can largely be cured by resection of the primary tumor and have a 5‐year survival rate exceeding 80%. In contrast, patients with lymph node metastases have a 5‐year survival rate below 50%, and the presence or absence of regional lymph node metastasis influences the chosen therapeutic regimen.…”

Section: Introductionmentioning

confidence: 99%

“…[13] On this basis, proteomic analyses have been applied to CRC in order identify diagnostic biomarkers and new therapeutic targets. [12,17,18] Previous proteomic analyses of CRC have variously defined differentially expressed proteins (DEPs) associated with the advancement of CRC, [1,2,6,12] with one study analyzing a single case of primary colon cancer and its synchronous liver metastasis. [6] Notwithstanding the findings of such studies, more work is still required to provide candidate CRC biomarkers as well as gaining better insights into its tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

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Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer

Guo

Wang

et al. 2020

Proteomics Clinical Apps

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Purpose: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it is sought to identify novel proteins as biomarkers and determinants of CRC metastasis. Experimental Design: Proteomic analyses are undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort. Results: Comparing CRC against paired normal adjacent tissues identifies 1559 differentially expressed proteins (DEPs) with 974 upregulated and 585 downregulated proteins, respectively. The highest number of DEPs is selectively associated with metastatic tumors (519 upregulated and 267 downregulated proteins, respectively) with a smaller number of unique DEPs identified only in non-metastatic CRC cases (116 upregulated and 29 downregulated proteins, respectively). The remaining DEPs are commonly expressed in both non-metastatic and metastatic tumors. The upregulation of three representative DEPs (S100A11, S100P, and RBM25) is confirmed using immunohistochemistry against 154 CRC tissues embedded in a tissue microarray. Conclusions and Clinical Relevance: The data reveal both previously identified CRC biomarkers along with novel candidates which provide a ready resource of DEPs in CRC for further investigation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer

Guo

Wang

et al. 2020

Proteomics Clinical Apps

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“…Consequently, ECM remodeling plays a crucial role in the formation of tumor and organ specific premetastatic niches and the adjustment of disseminated tumor cells to distant organs [9]. A recent study by Kim et al identified 58 differentially regulated proteins in CRC primary tumors and their respective solitary synchronous CRLM of which many were associated with the ECM [10], suggesting a crucial role of ECM proteins in colorectal cancer liver metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study by Kim et al . identified 58 differentially regulated proteins in CRC primary tumors and their respective solitary synchronous CRLM of which many were associated with the ECM [ 10 ], suggesting a crucial role of ECM proteins in colorectal cancer liver metastasis.…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer

Voß

Wurlitzer

Smit

et al. 2020

Clin Exp Metastasis

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Colorectal cancer (CRC) patients suffer from the second highest mortality among all cancer entities. In half of all CRC patients, colorectal cancer liver metastases (CRLM) can be observed. Metastatic colorectal cancer is associated with poor overall survival and limited treatment options. Even after successful surgical resection of the primary tumor, metachronous liver metastases occur in one out of eight cases. The only available curative intended treatment is hepatic resection, but metachronous CRLM frequently recur after approximately 1 year. In this study, we performed a proteome analysis of three recurrent liver metastases of a single CRC patient by mass spectrometry. Despite surgical resection of the primary CRC and adjuvant chemotherapy plus cetuximab treatment, the patient developed three metachronous CRLM which occurred consecutively after 9, 21 and 31 months. We identified a set of 1132 proteins expressed in the three metachronous CRLM, of which 481 were differentially regulated, including 81 proteins that were associated with the extracellular matrix (ECM). 56 ECM associated proteins were identified as upregulated in the third metastasis, 26 (46%) of which were previously described as negative prognostic markers in CRC, including tenascin C, nidogen 1, fibulin 1 and vitronectin. These data may reflect an ascending trend of malignancy from the first to the third metachronous colorectal cancer liver metastasis. Additionally, the results indicate different ECM phenotypes for recurrent metachronous metastasis, associated with different grades of malignancy and highlights the importance of individual analysis of molecular features in different, consecutive metastatic events in a single patient.

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“…The monoclonal antibodies like cetuximab, panitumumab, and bevacizumab have demonstrated effectiveness, both in terms of better response and improved survival. A comparison of various markers between primary and metastatic tumors have been recently reported [9][10][11][12][13]. Previous studies reported that while the immune microenvironment in the primary CRC tumor and liver metastasis is different, hypoxia-inducible factor-1α (HIF-1α) expression in primary CRC was comparable to that in corresponding metastases and HIF-1α expression is consistent in primary CRC and matched metastatic tissues [9,10].…”

Section: Introductionmentioning

confidence: 99%

HIF-1α expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis

et al. 2020

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Background The role of hypoxia-inducible factor-1α (HIF-1α) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1α expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). Methods Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1α expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1α expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. Results Activated HSCs induced HIF-1α mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1α expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1α expression in primary CRC. However, HIF-1α expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1α positive expression in liver metastasis had poor prognosis. Conclusion HIF-1α expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.

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Proteomic Analysis of Primary Colon Cancer and Synchronous Solitary Liver Metastasis

Cited by 32 publications

References 40 publications

Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer

Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer

Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer

HIF-1α expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis

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