Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival

BMC Cancer

Research

Mohammad A. Alqudah¹  Roba Bdeir²  Maha S. Al-Keilani³  Rana I. Elstaty⁴ 

[1] College of Medicine, Department of Microbiology, Pathology, and Forensic Medicine, The Hashemite University, P.O. Box 330127, 13133, Zarqa, Jordan;College of Nursing, Department of Allied Health Sciences, Al-Balqa Applied University, P.O. Box 206, Al-Salt 19117, Salt, Jordan;College of Pharmacy, Department of Clinical Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, 22110, Irbid, Jordan;College of Science and Art, Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, P.O. Box 3030, 22110, Irbid, Jordan;

关键词: Substance P;    Neurokinin 1 receptor;    Pyruvate kinase M2;    Ki-67;    Breast cancer;    Prognosis;    Biomarker;    Invasive ductal carcinoma;    Proliferation index;   

DOI  :  10.1186/s12885-023-10633-8

 received in 2022-09-26, accepted in 2023-02-11,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundChronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer.MethodsImmunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder.ResultsHigh SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047).ConclusionCombined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.

【 授权许可】

CC BY   
© The Author(s) 2023

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