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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

The studies included to investigate CXCR4 expression between HCC and normal hepatic tissues.Notes: Two hundred and forty-nine HCC patients and 101 normal liver specimen with the combined OR being 84.29 (95% CI =11.86–598.98, P<0.0001) are shown.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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f2-dddt-9-3625: The studies included to investigate CXCR4 expression between HCC and normal hepatic tissues.Notes: Two hundred and forty-nine HCC patients and 101 normal liver specimen with the combined OR being 84.29 (95% CI =11.86–598.98, P<0.0001) are shown.Abbreviations: CXCR4, C-X-C chemokine receptor 4; HCC, hepatocellular carcinoma; OR, odds ratio; CI, confidence interval; df, degree of freedom.

Mentions: The staining for CXCR4 was predominately a cytoplasmic staining and, in a few cases, an additional weak membranous or nuclear staining.11,12 We found that expression levels of CXCR4 are higher in HCC than those in normal hepatic tissues that serve as controls and cirrhosis patients. The pooled OR from six studies10,12,14,15,18–20 including 249 HCC patients and 101 normal controls is shown in Figure 2 (OR =84.26, 95% CI =11.86–598.98, P<0.0001). The “Events” in the second column means the number of HCC patients (described as “Total” in the third column) with CXCL4 positive expression. The “Events” in the fourth column means the number of normal individuals (described as “Total” in the fifth column) with CXCL4 positive expression. The OR is shown numerically in the seventh column, and the CI of the summary of OR does not include 1.0 (ie, 11.86–598.98) suggesting that the association is statistically significant. These findings that CXCR4 overexpresses in HCC tumor tissues but negatively expresses in normal tissues indicate that CXCR4 could be a diagnostic biomarker for HCC. The pooled OR from three studies14,17,19 including 127 HCC patients and 52 cirrhosis patients is shown in Figure 3A (OR =20.71, 95% CI =7.61–56.34, P<0.00001). The “Events” in the second column means the number of HCC patients (described as “Total” in the third column) with CXCL4 positive expression. The “Events” in the fourth column means the number of patients with cirrhosis (described as “Total” in the fifth column) with CXCL4 positive expression. The OR is shown numerically in the seventh column, and the CI of the summarized OR does not include 1.0 (ie, 7.61–56.34) suggesting that patients with HCC expressed significantly higher levels of CXCR4 than those with cirrhosis. The pooled OR from two studies14,19 including 36 cirrhosis patients and 26 normal controls is shown in Figure 3B (OR =3.82, 95% CI =0.62–23.55, P=0.15). The “Events” in the second column means the number of hepatic cirrhosis patients (described as “Total” in the third column) with CXCL4 positive expression. The “Events” in the fourth column means the number of normal individuals (described as “Total” in the fifth column) with CXCL4 positive expression. The OR is shown numerically in the seventh column, and the CI of the summarized OR includes 1.0 (ie, 0.62–23.55) suggesting that patients with hepatic cirrhosis expressed CXCR4 protein as high as those normal individuals. These findings indicate that CXCR4 expression in cirrhosis tissues is not significantly higher than that in normal tissues.


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)

The studies included to investigate CXCR4 expression between HCC and normal hepatic tissues.Notes: Two hundred and forty-nine HCC patients and 101 normal liver specimen with the combined OR being 84.29 (95% CI =11.86–598.98, P<0.0001) are shown.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

f2-dddt-9-3625: The studies included to investigate CXCR4 expression between HCC and normal hepatic tissues.Notes: Two hundred and forty-nine HCC patients and 101 normal liver specimen with the combined OR being 84.29 (95% CI =11.86–598.98, P<0.0001) are shown.Abbreviations: CXCR4, C-X-C chemokine receptor 4; HCC, hepatocellular carcinoma; OR, odds ratio; CI, confidence interval; df, degree of freedom.
Mentions: The staining for CXCR4 was predominately a cytoplasmic staining and, in a few cases, an additional weak membranous or nuclear staining.11,12 We found that expression levels of CXCR4 are higher in HCC than those in normal hepatic tissues that serve as controls and cirrhosis patients. The pooled OR from six studies10,12,14,15,18–20 including 249 HCC patients and 101 normal controls is shown in Figure 2 (OR =84.26, 95% CI =11.86–598.98, P<0.0001). The “Events” in the second column means the number of HCC patients (described as “Total” in the third column) with CXCL4 positive expression. The “Events” in the fourth column means the number of normal individuals (described as “Total” in the fifth column) with CXCL4 positive expression. The OR is shown numerically in the seventh column, and the CI of the summary of OR does not include 1.0 (ie, 11.86–598.98) suggesting that the association is statistically significant. These findings that CXCR4 overexpresses in HCC tumor tissues but negatively expresses in normal tissues indicate that CXCR4 could be a diagnostic biomarker for HCC. The pooled OR from three studies14,17,19 including 127 HCC patients and 52 cirrhosis patients is shown in Figure 3A (OR =20.71, 95% CI =7.61–56.34, P<0.00001). The “Events” in the second column means the number of HCC patients (described as “Total” in the third column) with CXCL4 positive expression. The “Events” in the fourth column means the number of patients with cirrhosis (described as “Total” in the fifth column) with CXCL4 positive expression. The OR is shown numerically in the seventh column, and the CI of the summarized OR does not include 1.0 (ie, 7.61–56.34) suggesting that patients with HCC expressed significantly higher levels of CXCR4 than those with cirrhosis. The pooled OR from two studies14,19 including 36 cirrhosis patients and 26 normal controls is shown in Figure 3B (OR =3.82, 95% CI =0.62–23.55, P=0.15). The “Events” in the second column means the number of hepatic cirrhosis patients (described as “Total” in the third column) with CXCL4 positive expression. The “Events” in the fourth column means the number of normal individuals (described as “Total” in the fifth column) with CXCL4 positive expression. The OR is shown numerically in the seventh column, and the CI of the summarized OR includes 1.0 (ie, 0.62–23.55) suggesting that patients with hepatic cirrhosis expressed CXCR4 protein as high as those normal individuals. These findings indicate that CXCR4 expression in cirrhosis tissues is not significantly higher than that in normal tissues.

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