The Prognostic Potential of Neurokinin 1 Receptor in Breast Cancer and Its Relationship with Ki-67 Index

Abstract

Background. Neurokinin 1 receptor (NK1R) is a promising biomarker and therapeutic target in breast cancer. This study was aimed at investigating the expression level of NK1R in breast cancer tissues and its relationship with proliferation index as measured by Ki-67, clinicopathological characteristics of patients, and overall survival rate. Methods. Immunohistochemical expression of NK1R and Ki-67 was measured in 164 paraffin-embedded breast cancer tissues of four molecular subtypes (42 HER2-enriched, 40 luminal A, 42 luminal B, and 40 triple negative). NK1R was scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff values for NK1R and Ki-67 were assessed by Cutoff Finder. Pearson’s Chi-square ( χ 2 ) and Fisher’s exact tests were used to compare the staining scores between groups. The Kaplan-Meier method with log-rank test was used for survival analysis. ANOVA and Student’s t -test were used to compare group means. Results. A total of 164 patients were included in the study which represented females with invasive ductal carcinoma. NK1R was expressed at high levels in about 34% of investigated cases. The mean Ki-67 level was about 27% and 41.5% of sample had high Ki-67 ( expression level > 22 % ). NK1R expression levels were associated with higher tumor grade ( p = 0.021 ) and high Ki-67 ( p = 0.012 ). NK1R expression negatively impacted overall survival in grade II tumors ( p = 0.027 ). Conclusion. NK1R contributes to cellular proliferation and is associated with negative prognosis in breast cancer. These findings suggest the potential role of NK1R as a therapeutic target in breast cancer.

Correlations between dynamic-enhanced magnetic resonance imaging quantitative parameters and postoperative recurrence or metastasis and clinicopathological features in breast cancer patients—a retrospective cohort study

“…A further analysis showed that peak time was more lowly expressed in high Ki-67 patients and more highly expressed in high ER and PR patients. As a high Ki-67 index is a risk factor for a poor prognosis in patients ( 21 ), while high ER and PR expression levels are protective factors for a poor prognosis ( 22 - 24 ), we indirectly illustrated that peak time is associated with patient prognosis.…”

The Neurokinin-1 Receptor: A Promising Antitumor Target

“…Tumor size and lymph-node metastasis relate to the number of fibers containing SP [96][97][98]. In breast cancer, the overexpression of SP is associated with a negative prognostic value, the expression of NK-1R with a high Ki-67 index (the nuclear Ki-67 protein is related to proliferative mechanisms), and higher tumor grade [99,100]. The data suggest that NK-1R and SP may serve as predictive cancer factors.…”

From pain to tumor immunity: influence of peripheral sensory neurons in cancer

“…Indeed, several studies have demonstrated that neuropeptide receptors are expressed on tumor cells, and their binding to neuropeptide ligands regulates various processes, including proliferation, survival, adhesion, and migration. This is particularly noteworthy, which have been shown to be involved in the progression of various cancer types, as shown in gastric, breast, and oral cancers, namely, through binding of SP to NK-1R expressed by tumor cells (213,221,(229)(230)(231)(232)(233)(234)(235)(236)(237)(238)(239)(240)(241)(242). Thus, sensory innervation could affect tumor growth not only by acting on tumor cells but also on tumor vascularization.…”