Prognostic and clinicopathological value of CXCL12/SDF1 expression in breast cancer: A meta-analysis

Liu, Heyang; Li, Zhuanzhen; Deng, Miao; Liu, Qipeng; Zhang, Ting; Guo, Wanying; Qiao, Weiqiang

doi:10.1016/j.cca.2018.05.041

Cited by 14 publications

(14 citation statements)

References 29 publications

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“…In female breast cancer, the cytoplasmic expression of CXCL12 was associated with better disease-free survival and OS [33,34]. These results are confirmed by a recently published meta-analysis, which included 8 studies with a total of 2205 patients [35]. Four of these studies (N = 953) measured the CXCL12 protein expression which was positively correlated with disease-free survival and OS.…”

Section: Discussionsupporting

confidence: 56%

High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

et al. 2020

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Background: Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival. Methods: From 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: Of 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49-0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45-0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47-0.88, P = 0.001). Conclusions: HGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future.

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Section: Discussionsupporting

confidence: 56%

High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

et al. 2020

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“…In addition to brain metastasis, a subset of breast cancer cells expressing C-X-C chemokine receptor (CXCR2) tend to metastasize to lung tissues rich in stromal cell-derived factor 1 (SDF1) (15). Although the role of the SDF1/CXCR4 axis in breast cancer metastasis has not been fully elucidated, the results from a previous meta-analysis suggested that the SDF1/CXCR4 protein expression level is a reliable prognostic biomarker for breast cancer (16). Bone and liver metastases (17,18) also play a critical role in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

Xiong

Chen

2019

Int J Mol Med

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To verify whether amyloid precursor protein (APP) affects the migration and invasion of breast cancer cell lines, and to understand its underlying mechanisms, epithelial-mesenchymal transition (EMT), the mitogen-activated protein kinase (MAPK) signaling pathway and the matrix metalloproteinase (MMP) family were investigated in MDA-MB-231, MCF-7 and BT474 human breast cancer cells. Breast cancer cell lines were transfected with plasmids containing APP coding sequences (pEGFP-n1-APP) and APP short hairpin RNA (pENTR APP shRNA). APP overexpres-sion efficiency, knockout efficiency and the expression levels of related genes were tested using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses. The effects of APP and mitogen-activated protein kinase kinase (MEK) inhibitor on cell migration and invasion were examined using Transwell assays. The results demonstrated that APP was significantly upregulated in the pEGFP-n1-APP group (P<0.05), and significantly downregulated in the pENTR APP shRNA group (P<0.05), compared with the control group. APP overexpression increased the migratory and invasive ability of human breast cancer cells (P<0.05), whereas APP silencing significantly inhibited cell migration and invasion (P<0.05). RT-qPCR and western blot analysis results suggested that APP overexpression significantly increased the expression of MMP-9, MMP-2, MMP-3, N-cadherin and vimentin (P<0.05). In addition, the enhanced expression of APP markedly affected the phosphorylation of mitogen-activated protein kinase kinase kinase 11 (MLK3), mitogen-activated protein kinase kinase 4 (MEK4) and mitogen-activated protein kinase 10 (JNK3; P<0.05). Additionally, APP overexpression had no effect on the total expression levels of MLK3, MEK4, and JNK3; however, APP overexpression significantly decreased the expression levels of E-cadherin and cytokeratin (P<0.05). Conversely, APP silencing had the opposite effects. When cells were treated with the MEK inhibitor PD0325901, the expression of APP was not altered, nor was the expression levels of MEK and its upstream signaling molecules. Taken together, the present findings suggested that APP could affect the migration and invasion of human breast cancer cells by mediating the activation of the MAPK signaling pathway, thereby promoting the EMT process.

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“…The virtual absence of CXCL12 protein in VSCC tumours was unexpected Original research as this chemokine was not only found in other tumour types, such as breast, ovarian or lung cancers, but was also shown to be of prognostic value. [44][45][46] Our finding could be linked to a fast turnover of CXCL12 protein within the cells, due to an increased abundance of ACKR3, which mediates ligand internalisation and its subsequent degradation. 47 48 By IHC, CXCL12 protein was detected in the blood vessels of nearly all of the analysed preinvasive vulvar lesions and VSCC tumours.…”

Section: Original Researchmentioning

confidence: 82%

“…The HPV status was determined, as described previously, 18 using the AmpliSens HPV HCR-genotype-titre-FRT kit (InterLabService), which detects 14 high-risk human papilloma virus (hrHPV) genotypes, namely, HPV16, 18,31,33,35,39,45,51,52,56,58,59, 66 and 68, following the manufacturer's instructions.…”

Section: Hpv Genotypingmentioning

confidence: 99%

CXCR4/ACKR3/CXCL12 axis in the lymphatic metastasis of vulvar squamous cell carcinoma

et al. 2021

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AimsVulvar squamous cell carcinoma (VSCC) spreads early and mainly locally via direct expansion into adjacent structures, followed by lymphatic metastasis to the regional lymph nodes (LNs). In the lymphatic metastasis, cancer cells bearing CXCR4 and ACKR3 (CXCR7) receptors are recruited to the LNs that produce the CXCL12 ligand. Our study aimed to assess the role of the CXCR4/ACKR3/CXCL12 axis in VSCC progression.MethodsTumour and LN tissue samples were obtained from 46 patients with VSCC and 51 patients with premalignant vulvar lesions. We assessed CXCR4, ACKR3 and CXCL12 by immunohistochemistry (IHC) in the tissue samples. Additionally, CXCL12 levels were determined by ELISA in the sera of 23 patients with premalignant lesions, 37 with VSCC and 16 healthy volunteers.ResultsCXCR4 and ACKR3 proteins were virtually absent in vulvar precancers, while in VSCC samples the IHC staining was strong. In the LNs of patients with VSCC, 98% of metastatic cells expressed CXCR4 and 85% expressed ACKR3. Neither CXCR4 nor ACKR3 presence was correlated with tumour human papilloma virus status. Few CXCL12-positive cells were found in the analysed tissue samples, but serum CXCL12 levels were significantly increased in both patients with premalignant vulvar lesions and with VSCC compared with healthy volunteers.ConclusionsIt appears that during progression and lymphatic spread of VSCC, the CXCR4/ACKR3/CXCL12 axis is activated. Moreover, our data suggest that CXCR4 antagonists merit further attention as a possible therapeutic option in patients with VSCC.

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Prognostic and clinicopathological value of CXCL12/SDF1 expression in breast cancer: A meta-analysis

Cited by 14 publications

References 29 publications

High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

CXCR4/ACKR3/CXCL12 axis in the lymphatic metastasis of vulvar squamous cell carcinoma

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