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 microenviron...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10633-8 |
| _version_ | 1797864423914733568 |
|---|---|
| author | Maha S. Al-Keilani Roba Bdeir Rana I. Elstaty Mohammad A. Alqudah |
| author_facet | Maha S. Al-Keilani Roba Bdeir Rana I. Elstaty Mohammad A. Alqudah |
| author_sort | Maha S. Al-Keilani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T22:51:31Z |
| format | Article |
| id | doaj.art-59fc4554da3142e3a5e45861e3a4ae62 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:51:31Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-59fc4554da3142e3a5e45861e3a4ae622023-03-22T11:35:27ZengBMCBMC Cancer1471-24072023-02-0123111510.1186/s12885-023-10633-8Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survivalMaha S. Al-Keilani0Roba Bdeir1Rana I. Elstaty2Mohammad A. Alqudah3College of Pharmacy, Department of Clinical Pharmacy, Jordan University of Science and TechnologyCollege of Nursing, Department of Allied Health Sciences, Al-Balqa Applied UniversityCollege of Science and Art, Department of Biotechnology and Genetic Engineering, Jordan University of Science and TechnologyCollege of Medicine, Department of Microbiology, Pathology, and Forensic Medicine, The Hashemite UniversityAbstract 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.https://doi.org/10.1186/s12885-023-10633-8Substance PNeurokinin 1 receptorPyruvate kinase M2Ki-67Breast cancerPrognosis |
| spellingShingle | Maha S. Al-Keilani Roba Bdeir Rana I. Elstaty Mohammad A. Alqudah 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 Substance P Neurokinin 1 receptor Pyruvate kinase M2 Ki-67 Breast cancer Prognosis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Substance P Neurokinin 1 receptor Pyruvate kinase M2 Ki-67 Breast cancer Prognosis |
| url | https://doi.org/10.1186/s12885-023-10633-8 |
| work_keys_str_mv | AT mahasalkeilani expressionofsubstancepneurokinin1receptorki67andpyruvatekinasem2inhormonereceptornegativebreastcancerandevaluationofimpactonoverallsurvival AT robabdeir expressionofsubstancepneurokinin1receptorki67andpyruvatekinasem2inhormonereceptornegativebreastcancerandevaluationofimpactonoverallsurvival AT ranaielstaty expressionofsubstancepneurokinin1receptorki67andpyruvatekinasem2inhormonereceptornegativebreastcancerandevaluationofimpactonoverallsurvival AT mohammadaalqudah expressionofsubstancepneurokinin1receptorki67andpyruvatekinasem2inhormonereceptornegativebreastcancerandevaluationofimpactonoverallsurvival |