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A meta-analysis for C-X-C chemokine receptor type 4 as a prognostic marker and potential drug target in hepatocellular carcinoma.

Hu F, Miao L, Zhao Y, Xiao YY, Xu Q - Drug Des Devel Ther (2015)

Bottom Line: CXCR4 expression is higher in HCC than those in cirrhosis as well, OR = 20.71, 95% CI = 7.61-56.34, P < 0.00001. 2) The expression levels of CXCR4 does not increase during local progression, however, CXCR4 expression increases the risk of distant metastases in HCC, OR = 5.84, 95% CI = 2.84-12.00, P < 0.00001. 3) High levels of CXCR4 gene expression are associated with worse survival in HCC, HR = 0.18, 95% CI = 0.10-0.32, Z = 5.77, P < 0.00001.The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of HCC.Our conclusion also supports that the promise of CXCR4 signaling pathway blockade as a potential strategy for HCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Chemokines (CKs), small proinflammatory chemoattractant cytokines that bind to specific G-protein coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. C-X-C chemokine receptor type 4 (CXCR4) has gained tremendous attention over the last decade, since it was found to be upregulated in a wide variety of cancer types, including hepatocellular carcinoma (HCC). The clinical relevance of expression of CXCR4 in HCC remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features. We searched the database from MEDLINE, PubMed, Web of Science, Scopus and Embase and then conducted a meta-analysis from publications met the inclusion criteria for the qualitative study. Our data showed that 1) CXCR4 is overexpressed in HCC tissues but not in normal hepatic tissue, OR = 84.26, 95% confidence interval (CI) = 11.86-598.98, P < 0.0001. CXCR4 expression is higher in HCC than those in cirrhosis as well, OR = 20.71, 95% CI = 7.61-56.34, P < 0.00001. 2) The expression levels of CXCR4 does not increase during local progression, however, CXCR4 expression increases the risk of distant metastases in HCC, OR = 5.84, 95% CI = 2.84-12.00, P < 0.00001. 3) High levels of CXCR4 gene expression are associated with worse survival in HCC, HR = 0.18, 95% CI = 0.10-0.32, Z = 5.77, P < 0.00001. These data indicate that CXCR4 expression correlates with an increased risk and worse survival in HCC patients. The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of HCC. Our conclusion also supports that the promise of CXCR4 signaling pathway blockade as a potential strategy for HCC patients.

No MeSH data available.


Related in: MedlinePlus

CXCR4 expression in the progression and metastasis of liver cancers.Notes: (A) Pooled results of expression of CXCR4 gene in the samples of different stages in HCC cancer. The pooled OR for local progression is shown (OR =1.9, 95% CI =0.48–7.57, P=0.36). (B) Pooled results of expression of CXCR4 gene in distant metastasis in HCC. The pooled OR from two included studies is shown (OR =5.84, 95% CI =2.84–12.00, Z=4.81, P<0.0001).Abbreviations: CXCR4, C-X-C chemokine receptor 4; HCC, hepatocellular carcinoma; OR, odds ratio; CI, confidence interval; df, degree of freedom.
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f4-dddt-9-3625: CXCR4 expression in the progression and metastasis of liver cancers.Notes: (A) Pooled results of expression of CXCR4 gene in the samples of different stages in HCC cancer. The pooled OR for local progression is shown (OR =1.9, 95% CI =0.48–7.57, P=0.36). (B) Pooled results of expression of CXCR4 gene in distant metastasis in HCC. The pooled OR from two included studies is shown (OR =5.84, 95% CI =2.84–12.00, Z=4.81, P<0.0001).Abbreviations: CXCR4, C-X-C chemokine receptor 4; HCC, hepatocellular carcinoma; OR, odds ratio; CI, confidence interval; df, degree of freedom.

Mentions: We observed that expression levels of CXCR4 did not increase during local progression as grouped as T3 + T4 vs T1 + T2 in HCC. The pooled OR from three studies11,12,17 including 259 HCC patients is shown in Figure 4A (OR =1.9, 95% CI =0.48–7.57, P=0.36). The “Events” in the second column means the number of HCC patients categorized as stages 3 and 4 (described as “Total” in the third column) expressing CXCL4 protein. The “Events” in the fourth column means the number of HCC patients categorized as stages 1 and 2 (described as “Total” in the fifth column) expressing CXCL4 protein. The OR is shown numerically in the seventh column, and the CI of the summarized OR includes 1.0 (ie, 0.48–7.57) suggesting that HCC patients at stages 3 and 4 expressed CXCR4 protein as high as those at stages 1 and 2. This suggests that strong CXCR4 expression did not correlate with local progression and proliferation of the primary tumor as indicated by the T-status. In two studies involved in the distant metastasis of HCC, CXCR4 expressions were increased in the specimens of distant metastasis. The pooled OR from two studies11,12 including 219 HCC patients is shown in Figure 4B (OR =5.84, 95% CI =2.84–12.00, P<0.00001). The “Events” in the second column means the number of HCC patients with distant metastasis (described as “Total” in the third column) expressing CXCL4 protein. The “Events” in the fourth column means the number of HCC patients without distant dissemination (described as “Total” in the fifth column) expressing CXCL4 protein. The OR is shown numerically in the seventh column, and the CI of the summarized OR does not include 1.0 (ie, 2.84–12.0) suggesting that HCC patients having distant metastasis expressed significantly much more CXCR4 protein than those just having limited local lesions. These data suggest that CXCR4 expression increases the risk of distant metastases in HCC.


A meta-analysis for C-X-C chemokine receptor type 4 as a prognostic marker and potential drug target in hepatocellular carcinoma.

Hu F, Miao L, Zhao Y, Xiao YY, Xu Q - Drug Des Devel Ther (2015)

CXCR4 expression in the progression and metastasis of liver cancers.Notes: (A) Pooled results of expression of CXCR4 gene in the samples of different stages in HCC cancer. The pooled OR for local progression is shown (OR =1.9, 95% CI =0.48–7.57, P=0.36). (B) Pooled results of expression of CXCR4 gene in distant metastasis in HCC. The pooled OR from two included studies is shown (OR =5.84, 95% CI =2.84–12.00, Z=4.81, P<0.0001).Abbreviations: CXCR4, C-X-C chemokine receptor 4; HCC, hepatocellular carcinoma; OR, odds ratio; CI, confidence interval; df, degree of freedom.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507792&req=5

f4-dddt-9-3625: CXCR4 expression in the progression and metastasis of liver cancers.Notes: (A) Pooled results of expression of CXCR4 gene in the samples of different stages in HCC cancer. The pooled OR for local progression is shown (OR =1.9, 95% CI =0.48–7.57, P=0.36). (B) Pooled results of expression of CXCR4 gene in distant metastasis in HCC. The pooled OR from two included studies is shown (OR =5.84, 95% CI =2.84–12.00, Z=4.81, P<0.0001).Abbreviations: CXCR4, C-X-C chemokine receptor 4; HCC, hepatocellular carcinoma; OR, odds ratio; CI, confidence interval; df, degree of freedom.
Mentions: We observed that expression levels of CXCR4 did not increase during local progression as grouped as T3 + T4 vs T1 + T2 in HCC. The pooled OR from three studies11,12,17 including 259 HCC patients is shown in Figure 4A (OR =1.9, 95% CI =0.48–7.57, P=0.36). The “Events” in the second column means the number of HCC patients categorized as stages 3 and 4 (described as “Total” in the third column) expressing CXCL4 protein. The “Events” in the fourth column means the number of HCC patients categorized as stages 1 and 2 (described as “Total” in the fifth column) expressing CXCL4 protein. The OR is shown numerically in the seventh column, and the CI of the summarized OR includes 1.0 (ie, 0.48–7.57) suggesting that HCC patients at stages 3 and 4 expressed CXCR4 protein as high as those at stages 1 and 2. This suggests that strong CXCR4 expression did not correlate with local progression and proliferation of the primary tumor as indicated by the T-status. In two studies involved in the distant metastasis of HCC, CXCR4 expressions were increased in the specimens of distant metastasis. The pooled OR from two studies11,12 including 219 HCC patients is shown in Figure 4B (OR =5.84, 95% CI =2.84–12.00, P<0.00001). The “Events” in the second column means the number of HCC patients with distant metastasis (described as “Total” in the third column) expressing CXCL4 protein. The “Events” in the fourth column means the number of HCC patients without distant dissemination (described as “Total” in the fifth column) expressing CXCL4 protein. The OR is shown numerically in the seventh column, and the CI of the summarized OR does not include 1.0 (ie, 2.84–12.0) suggesting that HCC patients having distant metastasis expressed significantly much more CXCR4 protein than those just having limited local lesions. These data suggest that CXCR4 expression increases the risk of distant metastases in HCC.

Bottom Line: CXCR4 expression is higher in HCC than those in cirrhosis as well, OR = 20.71, 95% CI = 7.61-56.34, P < 0.00001. 2) The expression levels of CXCR4 does not increase during local progression, however, CXCR4 expression increases the risk of distant metastases in HCC, OR = 5.84, 95% CI = 2.84-12.00, P < 0.00001. 3) High levels of CXCR4 gene expression are associated with worse survival in HCC, HR = 0.18, 95% CI = 0.10-0.32, Z = 5.77, P < 0.00001.The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of HCC.Our conclusion also supports that the promise of CXCR4 signaling pathway blockade as a potential strategy for HCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Chemokines (CKs), small proinflammatory chemoattractant cytokines that bind to specific G-protein coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. C-X-C chemokine receptor type 4 (CXCR4) has gained tremendous attention over the last decade, since it was found to be upregulated in a wide variety of cancer types, including hepatocellular carcinoma (HCC). The clinical relevance of expression of CXCR4 in HCC remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features. We searched the database from MEDLINE, PubMed, Web of Science, Scopus and Embase and then conducted a meta-analysis from publications met the inclusion criteria for the qualitative study. Our data showed that 1) CXCR4 is overexpressed in HCC tissues but not in normal hepatic tissue, OR = 84.26, 95% confidence interval (CI) = 11.86-598.98, P < 0.0001. CXCR4 expression is higher in HCC than those in cirrhosis as well, OR = 20.71, 95% CI = 7.61-56.34, P < 0.00001. 2) The expression levels of CXCR4 does not increase during local progression, however, CXCR4 expression increases the risk of distant metastases in HCC, OR = 5.84, 95% CI = 2.84-12.00, P < 0.00001. 3) High levels of CXCR4 gene expression are associated with worse survival in HCC, HR = 0.18, 95% CI = 0.10-0.32, Z = 5.77, P < 0.00001. These data indicate that CXCR4 expression correlates with an increased risk and worse survival in HCC patients. The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of HCC. Our conclusion also supports that the promise of CXCR4 signaling pathway blockade as a potential strategy for HCC patients.

No MeSH data available.


Related in: MedlinePlus