Current progress in the inflammatory background of angiogenesis in gynecological cancers

Szewczyk, Grzegorz; Maciejewski, T.; Szukiewicz, Dariusz

doi:10.1007/s00011-019-01215-1

Cited by 18 publications

(16 citation statements)

References 125 publications

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“…In recent years, increasing evidence has shown that activation of inflammation is a crucial mechanism for the recurrence and metastasis of gynecological [ 3 , 4 ] and breast [ 5 , 6 ] cancers. Thus, inflammatory-related peripheral cells measured in routine blood test (such as neutrophils, lymphocytes, and platelets) and their derived index [including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII, platelet count × neutrophil count/lymphocyte count)] may be potential prognostic biomarkers for gynecological and breast cancers.…”

Section: Introductionmentioning

confidence: 99%

Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis

Wang

2020

World J Surg Onc

102

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Background: Systemic immune-inflammation index (SII) has been suggested to be effective to reflect the inflammatory status and thus may be an underlying biomarker for prognosis prediction. This hypothesis has been demonstrated in meta-analyses on several cancer types. However, there was no study to confirm the prognostic roles of SII for gynecological and breast cancers, which was the goal of our study. Methods: PubMed, EMBASE, and Cochrane Library databases were searched to collect the articles exploring the associations of SII with prognostic outcomes [overall survival (OS), disease-free survival (DFS), progressionfree survival (PFS), lymph node metastasis (LNM), and lymphovascular invasion (LVI)] in gynecological and breast cancers. The prognostic value of SII was estimated by hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI). Results: Nine articles involving 2724 patients in 11 datasets were included. Meta-analysis showed that a high SII index was significantly associated with poor OS (HR = 2.12, 95% CI, 1.61-2.79, P < 0.001), DFS/PFS (HR = 2.28, 95% CI 1.52-3.41, P < 0.001) and an increased risk for LNM (RR = 1.34, 95% CI 1.20-1.50, P < 0.001) in patients with gynecological and breast cancers. Subgroup analysis confirmed the prognostic role of SII for OS was applicable to all cancer types, but the association with DFS/PFS and LNM was only significant for ovarian cancer and breast cancer, especially triple-negative breast cancer. No significant association was detected between SII and LVI. Conclusion: High SII may be a promising indicator for the prediction of poor prognosis in patients with gynecological and breast cancers, especially ovarian cancer and triple-negative breast cancer.

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Section: Introductionmentioning

confidence: 99%

Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis

Wang

2020

World J Surg Onc

102

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“…Accumulating evidence have showed that elevated NLR might be related to cancer growth and metastasis 19 , 20 , 27 , 42 . It is associated with poorer response to chemotherapy and radiotherapy, worse survival outcomes 6 .…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio is an independent predictor for survival outcomes in cervical cancer: a systematic review and meta-analysis

Zou

Yang

2020

Sci Rep

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This updated meta-analysis sought to explore whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could serve as an independent predictor for survival outcomes in patients with cervical cancer. We searched PubMed, Embase, Web of science and Scopus for studies on the association of pretreatment serum NLR with overall survival (OS) and progression-free survival (PFS) among patients with cervical cancer. Included studies with a hazard ratio (HR) and 95% confidence interval (CI) or a p-value were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to regions, NLR cut-off values and treatments. Publication bias was analyzed by Egger’s and Begg’s tests. A total of 14 studies comprising 6041 patients were included. The median cut-off value for NLR was 2.46 (range from 1.60 to 3.80). The higher NLR was associated to worse OS (HR 1.86, 95% CI 1.44–2.40) and PFS (HR 1.67, 95% CI 1.25–2.23), compared with lower NLR. This association still exited when analyzed according to regions, NLR cut-off values. Moreover, Significant association between NLR and OS was observed in studies which included patients with early stage disease and receiving radical surgeries. High NLR is independently associated with decreased OS and PFS in patients with cervical cancer. Pretreatment NLR is of independent value to predict the survival outcomes in patients with cervical cancer, regardless of regions and primary treatments.

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“…Generally, HPV-driven carcinogenesis represents a commonly acknowledged example of how chronic inflammation caused by a persistent infection becomes a driving force for tumor development [105]. It is also well accepted that an inflammatory response can contribute to the development of a vascular network within the tumor [106], including lymphatic vascular network [107], and EMT [108]. Besides, the members of the interferon-mediated antiviral response (interferon-stimulated genes, ISG) may facilitate tumor-associated lymphangiogenesis and enhance lymphatic metastasis capabilities [109].…”

Section: Discussionmentioning

confidence: 99%

Markers of Angiogenesis, Lymphangiogenesis, and Epithelial–Mesenchymal Transition (Plasticity) in CIN and Early Invasive Carcinoma of the Cervix: Exploring Putative Molecular Mechanisms Involved in Early Tumor Invasion

Kurmyshkina

Ковчур

Schegoleva

et al. 2020

IJMS

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The establishment of a proangiogenic phenotype and epithelial-to-mesenchymal transition (EMT) are considered as critical events that promote the induction of invasive growth in epithelial tumors, and stimulation of lymphangiogenesis is believed to confer the capacity for early dissemination to cancer cells. Recent research has revealed substantial interdependence between these processes at the molecular level as they rely on common signaling networks. Of great interest are the molecular mechanisms of (lymph-)angiogenesis and EMT associated with the earliest stages of transition from intraepithelial development to invasive growth, as they could provide the source of potentially valuable tools for targeting tumor metastasis. However, in the case of early-stage cervical cancer, the players of (lymph-)angiogenesis and EMT processes still remain substantially uncharacterized. In this study, we used RNA sequencing to compare transcriptomes of HPV(+) preinvasive neoplastic lesions and early-stage invasive carcinoma of the cervix and to identify (lymph-)angiogenesis- and EMT-related genes and pathways that may underlie early acquisition of invasive phenotype and metastatic properties by cervical cancer cells. Second, we applied flow cytometric analysis to evaluate the expression of three key lymphangiogenesis/EMT markers (VEGFR3, MET, and SLUG) in epithelial cells derived from enzymatically treated tissue specimens. Overall, among 201 differentially expressed genes, a considerable number of (lymph-)angiogenesis and EMT regulatory factors were identified, including genes encoding cytokines, growth factor receptors, transcription factors, and adhesion molecules. Pathway analysis confirmed enrichment for angiogenesis, epithelial differentiation, and cell guidance pathways at transition from intraepithelial neoplasia to invasive carcinoma and suggested immune-regulatory/inflammatory pathways to be implicated in initiation of invasive growth of cervical cancer. Flow cytometry showed cell phenotype-specific expression pattern for VEGFR3, MET, and SLUG and revealed correlation with the amount of tumor-infiltrating lymphocytes at the early stages of cervical cancer progression. Taken together, these results extend our understanding of driving forces of angiogenesis and metastasis in HPV-associated cervical cancer and may be useful for developing new treatments.

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Current progress in the inflammatory background of angiogenesis in gynecological cancers

Cited by 18 publications

References 125 publications

Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis

Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis

Neutrophil-to-lymphocyte ratio is an independent predictor for survival outcomes in cervical cancer: a systematic review and meta-analysis

Markers of Angiogenesis, Lymphangiogenesis, and Epithelial–Mesenchymal Transition (Plasticity) in CIN and Early Invasive Carcinoma of the Cervix: Exploring Putative Molecular Mechanisms Involved in Early Tumor Invasion

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