CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Goto, Masakazu; Yoshida, Takahiro; Yamamoto, Yota; Furukita, Yoshihito; Inoue, Seiya; Fujiwara, Satoshi; Kawakita, Naoya; Nishino, Takeshi; Minato, Takuya; Yuasa, Yasuhiro; Yamai, Hiromichi; Takechi, Hirokazu; Seike, Junichi; Bando, Yoshimi; Tangoku, Akira

doi:10.1245/s10434-015-4974-5

Cited by 36 publications

(29 citation statements)

References 33 publications

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“…Our data indicate that determination of CXCL12 expression could be useful for predicting outcome in these cancer types. Although studies of RNA expression were excluded from this meta-analysis, published studies that have assessed CXCL12 mRNA expression in oesophageal (Goto et al , 2017) or breast cancer (Razis et al , 2012) support our findings, with an association between increased CXCL12 expression and adverse outcome in oesophageal cancer, but the converse in breast cancer.…”

Section: Discussionsupporting

confidence: 73%

A meta-analysis of CXCL12 expression for cancer prognosis

et al. 2017

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Background:CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed.Methods:We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival.Results:Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective. The pooled hazard ratios (HRs) for overall and recurrence-free survival in patients with high CXCL12 expression were 1.39 (95% CI: 1.17–1.65, P=0.0002) and 1.12 (95% CI: 0.82–1.53, P=0.48) respectively, but with significant heterogeneity between studies. On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31–3.33, P=0.002), pancreatic (HR 1.54; 95% CI: 1.21–1.97, P=0.0005) and lung cancer (HR 1.37; 95% CI: 1.08–1.75, P=0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38–0.66, P<0.00001).Conclusions:Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types. Prospective or prospective–retrospective analyses of CXCL12 expression in clearly defined cancer cohorts are now required to advance our understanding of the relationship between CXCL12 expression and cancer outcome.

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Section: Discussionsupporting

confidence: 73%

A meta-analysis of CXCL12 expression for cancer prognosis

et al. 2017

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“…Xue T et al stratified the data based on the combination of CXCR7 expression with low HNF4α expression and relative degree of differentiation of cancer and these data were also analyzed separately. Among 27 studies, three studies each evaluated colorectal carcinoma (or rectal cancer) 18 - 20 , hepatocellular carcinoma 21 - 23 , esophageal carcinoma (or esophageal squamous cell carcinoma) 13 , 24 , 25 , and thyroid carcinoma 26 - 28 . Two studies evaluated renal cell carcinoma 29 , 30 , pancreatic cancer 31 , 32 , cervical cancer (or cervical squamous cell carcinoma) 33 , 34 , nasopharyngeal carcinoma 35 , 36 , glioma or glioblastoma 37 , 38 and gastric cancer 39 , 40 .…”

Section: Meta-analysis Resultsmentioning

confidence: 99%

Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Zhao¹,

Zhang²,

Qin³

et al. 2018

J. Cancer

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Background: Accumulating evidence indicated that the CXC chemokine receptor (CXCR) 7 (CXCR7) was overexpressed in a variety of tumors. However, the value of the CXCR7 expression in predicting prognosis in solid tumors remains controversial. Therefore, we performed this meta-analysis to evaluate the correlation between CXCR7 expression and lymph node metastasis (LNM), tumor pathological grade and survival, including overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS).Methods: Eligible studies were searched in PubMed, Web of Science, and PMC up to April 2018. A total of 27 studies were included in this meta-analysis. Odds ratio (OR), hazard ratio (HR) and 95 % confidence intervals (CI) were used as effect measures.Results: The meta-analysis showed that high expression of CXCR7 predicted a high risk of LNM (pooled OR = 2.22, 95%CI: 1.41-3.50), high tumor grade (pooled OR = 1.94, 95%CI: 1.20-3.13), poor OS (pooled HR = 1.66, 95%CI: 1.30-2.03), and poor DFS/RFS (pooled HR = 1.82, 95%CI: 1.21-2.43). Subgroup analysis showed that CXCR7 expression had a positive correlation with LNM in pan-adenocarcinoma subgroup (pooled OR = 3.73, 95%CI: 2.21-6.30), while no correlation was found in pan-squamous cancer subgroup (pooled OR = 1.29, 95%CI: 0.56-2.96). Subgroup analysis of tumor grade revealed that high expression of CXCR7 predicted high tumor grade both in pan-squamous cancer and pan-adenocarcinoma (pooled OR = 3.58, 95%CI: 1.39-9.22, pooled OR = 2.25, 95%CI: 1.20-4.20). As in OS group, we divided the data based on analysis method and it turned out that overexpressed CXCR7 predicted worse OS both in multivariate analysis (pooled HR =1.57, 95%CI: 1.12-2.01) and univariate analysis subgroup (pooled HR =1.86, 95%CI: 1.23-2.49).Conclusions: Our meta-analysis revealed that high expression of CXCR7 predicted unfavorable prognosis and may serve as potential targets of cancer therapy.

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“…In the case of tumor metastasis, CXCL12 is released from stromal cells within the metastatic microenvironment, which in turn activates CXCR4 on cancer cells to increase cancer cell adhesion, motility and invasion in colon cancer cells [8]. Indeed, CXCR4 expression is an independent prognostic marker for several malignancies including: AML, multiple myeloma, squamous cell carcinoma, gastric cancer, renal cancer, hepatocellular carcinoma, and colorectal cancer (CRC) [31][32][33][34][35][36][37]. In the case of CRC patients, a meta-analysis correlated high CXCR4 expression with liver and lymph node metastasis and ultimately a reduction in overall survival [38].…”

Section: Introductionmentioning

confidence: 99%

Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer

Stuckel

Zhang

et al. 2020

Cancers

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In colorectal cancer (CRC), upregulation of the C-X-C motif chemokine receptor 4 (CXCR4) is correlated with metastasis and poor prognosis, highlighting the need to further elucidate CXCR4’s regulation in CRC. For the first time, DNA methylation and 5-hydroxymethylcytosine aberrations were investigated to better understand the epigenetic regulation of CXCR4 in CRC. CXCR4 expression levels were measured using qPCR and immunoblotting in normal colon tissues, primary colon cancer tissues and CRC cell lines. Publicly available RNA-seq and methylation data from The Cancer Genome Atlas (TCGA) were extracted from tumors from CRC patients. The DNA methylation status spanning CXCR4 gene was evaluated using combined bisulfite restriction analysis (COBRA). The methylation status in the CXCR4 gene body was analyzed using previously performed nano-hmC-seal data from colon cancers and adjacent normal colonic mucosa. CXCR4 expression levels were significantly increased in tumor stromal cells and in tumor colonocytes, compared to matched cell types from adjacent normal-appearing mucosa. CXCR4 promoter methylation was detected in a minority of colorectal tumors in the TCGA. The CpG island of the CXCR4 promoter showed increased methylation in three of four CRC cell lines. CXCR4 protein expression differences were also notable between microsatellite stable (MSS) and microsatellite instable (MSI) tumor cell lines. While differential methylation was not detected in CXCR4, enrichment of 5-hydroxymethylcytosine (5hmC) in CXCR4 gene bodies in CRC was observed compared to adjacent mucosa.

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CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Abstract: CXCR4 expression is associated with poor prognosis in patients with ESCC.

Cited by 36 publications

References 33 publications

A meta-analysis of CXCL12 expression for cancer prognosis

A meta-analysis of CXCL12 expression for cancer prognosis

Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer

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