CXC chemokine ligand 4 (CXCL4) is predictor of tumour angiogenic activity and prognostic biomarker in non-small cell lung cancer (NSCLC) patients undergoing surgical treatment

Špaks, Artjoms; Svirina, Darja; Spaka, Irina; Jaunalksne, Inta; Breiva, Donats; Tracums, Ilmars; Krieviņš, Dainis

doi:10.3109/1354750x.2016.1172111

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…Cumulative evidence has revealed that chemokines can modulate tumor immunity and modulate tumor immunological and biological phenotypes in direct and indirect ways, thus affecting angiogenesis, tumorigenesis, progression, metastasis, therapeutic effect, and patient outcomes (7,(9)(10)(11). As an important part of the chemokine family, CXC chemokines are potential therapeutic targets, and prognostic biomarkers for many types of tumors, including RCC (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Zeng¹,

Sun

Li³

et al. 2020

Front. Oncol.

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Background: Renal cell carcinoma (RCC) is one of the most common malignances with an ever-increasing incidence and high mortality. Cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC chemokines in the tumor microenvironment can modulate immune cell trafficking and regulate tumor cell activities, thus exerting anti-tumor immunological effects and affecting patient outcomes; however, the expression and prognostic values of CXC chemokines in RCC have not been clarified. Methods: ONCOMINE, GEPIA, UALCAN, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRRUST, LinkedOmics, and TIMER were utilized in this study. Results: The transcriptional levels of CXCL1/2/5/6/9/10/11/16 in RCC tissues were significantly elevated while the transcriptional levels of CXCL3/7/12/13 were significantly reduced. A significant correlation was found between the expression of CXC1/5/9/10/11/13 and the pathological stage of RCC patients. RCC patients with low transcriptional levels of CXCL1/2/3/5/13 were associated with a significantly better prognosis. The functions of differentially expressed CXC chemokines are primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the SRC family of tyrosine kinases (LCK, LYN, and FYN), mitogen-activated protein kinases (MAPK1 and MAPK3), and CSNK1D are CXC chemokine targets. We found significant correlations among the expression of CXC chemokines and the infiltration of six types of immune cells (B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells). Conclusions: Our results may provide novel insights for the selection of immunotherapeutic targets and prognostic biomarkers for renal cell carcinoma.

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Section: Introductionmentioning

confidence: 99%

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Zeng¹,

Sun

Li³

et al. 2020

Front. Oncol.

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“…Previous research by our group has confirmed diagnostic and prognostic value of CXC chemokines as biomarkers (7,8).…”

Section: Introductionmentioning

confidence: 99%

Role of CXC group chemokines in lung cancer development and progression

Špaks

2017

J. Thorac. Dis.

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Background: Clinical and translational research on lung cancer patients undergoing surgical treatment can provide valuable scientific data and unique opportunity to study tumor microenvironment. CXC chemokines, which are members of a big family of cytokines, are undoubtedly involved in tumor growth regulation and metastasizing pathways. For better understanding of CXC chemokine involvement in the process of carcinogenesis we have studied the cohort of early stage non-small cell lung cancer patients undergoing surgery with curative intent. Our aim was to assess CXC chemokine ligand (CXCL) levels in patient blood samples representing systemic circulation and tumor microenvironment; assess CXC chemokine receptor (CXCR) expression in tumor tissue; and measure tumor infiltrating immune cell subpopulations.Methods: A total of 54 patients with NSCLC had radical lung resection were enrolled in a single center prospective study and were followed-up annually for up to six years. During surgical procedure peripheral and tumor draining blood samples were taken. CXCL1, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12 levels were determined by ELISA, and chemokine concentration gradient was calculated. Tumor infiltrating immune cells (T helper cells, T cytotoxic cells, macrophages, B cells, plasma cells) and expression of CXCR1, CXCR2, CXCR3 and CXCR4 in tumor tissue were assessed by immunohistochemistry. Results: Statistically significant decrease in chemokine concentration was found for CXCL4 (P=0.002) and CXCL5 (P=0.011), and statistically significant concentration increase was found for CXCL7 (P=0.001) in total cohort. We have found statistically significant CXC chemokine concentration change for majority of chemokines-CXCL1 (P=0.002), CXCL4 (P=0.001), CXCL5 (P=0.013), CXCL7 (P=0.036), CXCL8 (P=0.026), CXCL9 (P=0.034) and CXCL10 (P=0.032) in a group of patients who had good clinical result after surgery with no evidence of relapse, on the other hand patients with cancer recurrence including local and systemic cancer spread did not show any change of chemokine concentration in blood except for CXCL1 (P=0.041). We have also found that chemokine levels and gradients correlate with CXC receptor expression and number of tumor infiltrating immune cell subpopulations Conclusions: Assessment of tumor microcirculation is useful for evaluation of different types of circulating biomarkers and application of our method can be very wide, integrating thoracic surgeons into translational cancer research.

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“…15 Nevertheless, a recent study on 50 nonsmall cell lung cancer patients reported that circulating CXCL4 levels correlate with tumor vascularity, and increased levels in these patients associated with relapse and worse outcome. 16 Similarly, we have previously found that a high level of circulating CXCL4 correlates with poorer survival in a small cohort consisting of 33 OS patients. 9 Given that our previous result contradicted most of the literature, which suggests a correlation between high CXCL4 levels and better patient outcome, in this study we decided to employ a large multi-institutional cohort to better determine the prognostic role of circulating CXCL4 in OS.…”

Section: Discussionmentioning

confidence: 64%

“…Similarly, lung CXCL4 levels are decreased in the premetastatic stage of melanoma and breast cancer animal models, and its levels negatively correlate with tumor stage and positively correlated with cancer patient survival . Nevertheless, a recent study on 50 nonsmall cell lung cancer patients reported that circulating CXCL4 levels correlate with tumor vascularity, and increased levels in these patients associated with relapse and worse outcome . Similarly, we have previously found that a high level of circulating CXCL4 correlates with poorer survival in a small cohort consisting of 33 OS patients .…”

Section: Discussionmentioning

confidence: 67%

The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma

Flores

Kelly

et al. 2017

Pediatric Blood & Cancer

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BACKGROUND Osteosarcoma is the most common pediatric bone cancer. Despite advances in treatment regimens, the survival rate remains 60–70%. There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. PROCEDURE Our lab has previously identified that circulating Serum Amyloid A (SAA) and CXC Chemokine Ligand 4 (CXCL4) are upregulated in patients with osteosarcoma. In this study, we tested if they could be used as prognostic biomarkers. We used ELISAs to measure their concentrations in serum samples (n = 233), and immunohistochemistry to examine expressions in primary tumors (n = 37). Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. RESULTS Patients with “High SAA” and “Low CXCL4” circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, p = 0.014), which was independent of the metastatic status. These patients also exhibited a significantly higher rate of poor histological response to chemotherapy. Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, p = 0.005). CONCLUSIONS Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in osteosarcoma. Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in osteosarcoma.

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CXC chemokine ligand 4 (CXCL4) is predictor of tumour angiogenic activity and prognostic biomarker in non-small cell lung cancer (NSCLC) patients undergoing surgical treatment

Abstract: Plasma levels of CXCL4 are associated with tumour vascularity. Increased CXCL4 levels in NSCLC patients undergoing treatment may indicate active cancer-induced angiogenesis associated with relapse and worse outcome.

Cited by 17 publications

References 19 publications

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Role of CXC group chemokines in lung cancer development and progression

The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma

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