NILCO biomarkers in breast cancer from Chinese patientsReport as inadecuate

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BMC Cancer

, 14:249

Translational oncology


BackgroundNotch, IL-1 and leptin are known pro-angiogenic factors linked to breast cancer development, tumor aggressiveness and poor prognosis. A complex crosstalk between these molecules NILCO has been reported in breast cancer cell lines. However, whether NILCO biomarkers are differentially expressed in estrogen responsive ER+, unresponsive ER- and triple negative TNBC breast cancer tissues is unknown.

MethodsExpression levels of nine NILCO and targets Notch1, Notch4, JAG1, DLL4, VEGF, VEGFR2 FLK-1, leptin, leptin receptor OB-R and interleukin-1 receptor type I IL-1R tI were examined via immunohistochemistry in breast cancer tissue microarrays from Chinese patients ER+, n=33; ER-, n=21; TNBC, n=13 and non-malignant breast tissue n=5; Pantomics, Inc. using a semi-quantitative analysis of intensity staining, HSCORE.

ResultsCategorical expression of NILCO and targets + or - was similar among all cancer tissues. However, TNBC showed differential localization pattern of NILCO. TNBC showed fewer nuclei and cytoplasms positive for Notch4 and JAG1, but more cytoplasms positive for leptin. In addition, fewer TNBC stromas were positive for Notch1 and Notch4, but 100% of TNBC stromas were positive for VEGFR2. Moreover, TNBC had lower DLL4 and IL-1R tI expression. TNBC and ER- showed higher expression of EGFR, but lower expression of AR. Leptin and OB-R were detected in more than 61% of samples. Leptin positively correlated to OB-R, JAG1, VEGF, and marginally to IL-1R tI. Notch1 positively correlated to IL-1R tI. EGFR and Ki67 were positively associated to Notch1, but no associations of NILCO and targets with p53 were found.

ConclusionsPresent data suggest that NILCO components are differentially expressed in breast cancer. TNBC showed distinctive patterns for NILCO expression and localization. The complex crosstalk between leptin, IL-1 and Notch could differentially drive breast cancer growth and angiogenesis. Furthermore, the analysis of NILCO and targets using Pathway Studio9 software Ariadine Genomics showed multiple molecular relationships that suggest NILCO has potential prognostic biomarker value in breast cancer.

AbbreviationsOB-RLeptin receptor

IL-1R tIInterleukin 1 receptor type I

NILCONotch interleukin 1 leptin crosstalk outcome

EGFREpidermal growth factor receptor

NANOGA homeobox protein and transcription factor

SOX2Sex determining region Y-box 2 protein

OCT4Octamer-binding transcription factor 4

IGF-1RInsulin like growth factor receptor 1

EREstrogen receptor

ARAndrogen receptor

PRProgesterone receptor

HER2Epidermal growth factor receptor 2

DLL4Delta like notch ligand 4

JAG1Jagged 1 protein a Notch ligand

VEGFVascular endothelial growth factor

VEGFR2Vascular endothelial growth factor receptor 2 or KDR

TNBCTriple negative breast cancer cells

HSCOREA semi-quantitative analysis of intensity staining.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-249 contains supplementary material, which is available to authorized users.

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Author: Laronna S Colbert - Kaamilah Wilson - Sungjin Kim - Yuan Liu - Gabriela Oprea-Ilies - Corey Gillespie - Toi Dickson - Gale


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