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

Abstract

Background Chronic 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. Methods Immunohistochemical 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. Results High 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). Conclusion Combined 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.

Platelet Membrane-Camouflaged Silver Metal–Organic Framework Biomimetic Nanoparticles for the Treatment of Triple-Negative Breast Cancer

“…Ki-67, a vital and effective index for evaluating tumor cell proliferation, has been validated as an independent predictor and prognostic factor in breast cancer . Additionally, Ki-67 is notably overexpressed in estrogen receptor (ER)-negative cells. , The counts of Ki-67-positive cells decreased significantly following PM@MOF-Ag NP administration, as shown in Figure B. Furthermore, in vitro flow cytometry and DCF probe staining revealed that PM@MOF-Ag NPs induced ROS overproduction, leading to tumor cell apoptosis.…”

The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant

“…Many studies have demonstrated that NK-1R antagonists counteract the side effects of chemotherapy and radiotherapy and that SP/NK-1R mediate cancer chemoresistance through Notch 1, Raf/MEK/ERK and PI3K/Akt/mTOR and MAPK signaling pathways [7,9,144]. These pathways promote cell proliferation, regulate cell metabolism, block apoptosis, and are crucial in cancer chemoresistance [145,146]. Therefore, the SP/NK-1R system is a potential target to increase the response to anticancer immunotherapies [7].…”