Genomic-wide analysis of lymphatic metastasis-associated genes in human hepatocellular carcinoma

Lee, Chun Feng; Ling, Zhi Qiang; Zhao, Ting; Fang, Shih-Hua; Chang, Wen Shin; Lee, San Chih; Lee, Kuan Rong

doi:10.3748/wjg.15.356

Cited by 52 publications

(39 citation statements)

References 47 publications

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“…Also our "Up in Metastatic" signature revealed elevated levels of solute carrier proteins, namely SLC25A5 and SLC25A3. The former has been implicated earlier to be elevated in lymph node metastasis associated with hepatocellular carcinoma (81), whereas SLC25A3 serves as the mitochondrial transporter for phosphate (82). Interestingly, independent metabolomics data for prostate cancer progression generated by our laboratory revealed significantly elevated levels of inorganic phosphate in tumors, corroborating with the finding of elevated levels of phosphate carrier in metastatic prostate cancer (83).…”

Section: Discussionsupporting

confidence: 79%

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer

Khan

Poisson

Bhat

et al. 2010

Molecular & Cellular Proteomics

117

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Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. Molecular & Cellular Proteomics 9:298 -312, 2010.

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Section: Discussionsupporting

confidence: 79%

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer

Khan

Poisson

Bhat

et al. 2010

Molecular & Cellular Proteomics

117

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“…Downregulation of PTPN2 has been previously shown in different types of cancer. In hepatocellular carcinoma, loss of PTPN2 was correlated with presence of lymph node metastasis [36]. PTPN2 loss through gene deletions or mutations have been reported in T-cell acute lymphoblastic leukaemia (T-ALL) and peripheral T-cell lymphoma not otherwise specified, and has been coupled to increased cytokine sensitivity and proliferation through stimulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) -signalling pathways [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Karlsson

Veenstra

Emin

et al. 2015

Breast Cancer Res Treat

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Gene copy loss of PTPN2 was detected in 16% (34/215) of the tumours and this was significantly correlated with lower levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a significant predictive marker of poor benefit from tamoxifen treatment.In conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical marker of endocrine treatment benefit which could guide further individualised therapies in breast cancer.

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“…It has been reported that genes favoring metastasis progression are initiated in the peritumoral liver microenvironment of HCC (9,13). Further, Lee and colleagues reported that frozen HCC tissue can provide genome-wide information that contributes to an improved understanding of molecular alterations during LNM in HCC (27). In this study, we evaluated gene expression in primary tumors and in the peritumoral liver microenvironment and identified 83 genes that were differentially expressed between the LNM and NLNM groups.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Fixed Tissues Identified Hypoxia-Inducible Factor-1α, VEGF, and Matrix Metalloproteinase-2 as Biomarkers of Lymph Node Metastasis in Hepatocellular Carcinoma

Xiang

Ren

Fan

et al. 2011

Clinical Cancer Research

112

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Purpose: Hepatocellular carcinoma (HCC) most often develops in patients infected with hepatitis B or hepatitis C virus. Differential gene expression profiling is useful for investigating genes associated with lymph node metastasis (LNM). We screened genes to identify potential biomarkers for LNM in HCC.Experimental Design: RNA was extracted from formalin-fixed specimens of paired intratumoral and peritumoral tissues of patients with lymph node-positive (n ¼ 36) or negative (n ¼ 36) HCC. A cDNAmediated annealing, selection, extension, and ligation assay was done with an array of 502 known cancerrelated genes to identify differentially expressed genes in 20 pairs of patients with or without LNM. Candidate biomarkers were evaluated by using immunohistochemistry and tissue microarrays in an independent cohort of 309 HCC patients who had undergone hepatectomy. Of the 309 patients, 235 (76.1%) patients were infected with hepatitis B.Results: Compared with lymph node-negative patients, lymph node-positive patients had 17 overexpressed genes and 19 underexpressed genes in intratumoral tissues, and 25 overexpressed genes and 22 underexpressed genes in peritumoral tissues. Hypoxia-inducible factor (HIF)-1a, VEGF, and matrix metalloproteinase (MMP)-2 were selected for analysis in the cohort of 309 HCC patients. We found that intratumoral protein levels of HIF-1a, VEGF, and MMP-2 were independent risk factors for developing LNM.Conclusion: We identified 83 cancer genes that were differentially expressed in lymph node-positive and lymph node-negative HCC. Our findings show that the combination of intratumoral HIF-1a, VEGF, and MMP-2 may be useful as a molecular prediction model for LNM.

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Genomic-wide analysis of lymphatic metastasis-associated genes in human hepatocellular carcinoma

Cited by 52 publications

References 47 publications

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Gene Expression Profiling of Fixed Tissues Identified Hypoxia-Inducible Factor-1α, VEGF, and Matrix Metalloproteinase-2 as Biomarkers of Lymph Node Metastasis in Hepatocellular Carcinoma

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