Articles
Vol. 70 No. 3 (2026)
https://doi.org/10.4081/ejh.2026.4599

Histopathological evaluation of RPL5 expression in triple-negative breast cancer: an integrated immunohistochemical and transcriptomic study

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Published: 23 July 2026
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Triple-negative breast cancer, RPL5, immunohistochemistry, ribosome biogenesis, TCGA, transcriptomic analysis, p53 signaling pathway

Authors

Bing Zhao
doctorcrystal@163.com
Department of Breast Cancer, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Peiyuan Yu
Department of Breast Cancer, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Li Li
Department of Breast Cancer, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Zhenhui Zhao
Department of Breast Cancer, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Xiner Zhang
Department of Breast Cancer, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasiveness, limited therapeutic options, and unfavorable clinical outcomes. Ribosomal protein L5 (RPL5), a component of the large ribosomal subunit, has been implicated in ribosome biogenesis, translational regulation, and p53-associated cellular processes. This study investigated the immunohistochemical expression pattern of RPL5 in TNBC tissues and explored its potential biological significance through integrated transcriptomic analyses. Tumor tissues from 37 patients with TNBC and 7 adjacent non-tumorous breast tissues were collected from the Affiliated Tumor Hospital of Xinjiang Medical University between December 2017 and December 2023. RPL5 protein expression was evaluated by immunohistochemistry, and its association with clinicopathological characteristics was analyzed. Public transcriptomic datasets from TCGA-BRCA and GEO were further used to validate RPL5 expression patterns in TNBC. Co-expression analysis and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate potential biological functions and signaling pathways associated with RPL5. Immunohistochemical analysis demonstrated significantly lower RPL5 protein expression in TNBC tissues compared with adjacent normal breast tissues (p=0.001). In contrast, transcriptomic analyses revealed significantly higher RPL5 expression in TNBC compared with non-TNBC breast cancer subtypes (p<0.001). No significant associations were observed between RPL5 expression and clinicopathological parameters, including age, tumor size, menopausal status, TNM stage, histological grade, or lymph node metastasis (all p>0.05). Survival analysis showed no significant difference in overall survival between patients with high and low RPL5 expression. Functional enrichment analyses indicated that RPL5-related genes were predominantly involved in ribosome biogenesis, translational regulation, and p53-related signaling pathways. These findings suggest that abnormal RPL5 expression may be associated with TNBC biology through ribosome-related programs, although causal roles require functional validation. RPL5 may represent a potential histopathological and molecular indicator associated with TNBC biology, although its precise functional role requires further experimental validation.

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1. Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 2020;22:61. DOI: https://doi.org/10.1186/s13058-020-01296-5
2. Karim AM, Eun Kwon J, Ali T, Jang J, Ullah I, Lee YG, et al. Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies. Biochem Pharmacol 2023;212:115545. DOI: https://doi.org/10.1016/j.bcp.2023.115545
3. Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer - expanded options, evolving needs. Nat Rev Clin Oncol 2022;19:91-113. DOI: https://doi.org/10.1038/s41571-021-00565-2
4. Howard FM, Olopade OI. Epidemiology of triple-negative breast cancer: a review. Cancer J 2021;27:8-16. DOI: https://doi.org/10.1097/PPO.0000000000000500
5. Tong D, Zhang J, Wang X, Li Q, Liu LY, Yang J, et al. MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription. Oncogenesis 2020;9:56. DOI: https://doi.org/10.1038/s41389-020-0239-7
6. Oršolić I, Bursać SAN, Jurada D, Drmić Hofman I, Dembić Z, Bartek J, et al. Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint. Oncogene 2020;39:3443-57. DOI: https://doi.org/10.1038/s41388-020-1231-6
7. Xie C, Liang XL, Chen B, Chen S, Xiong FX, Wang QC, et al. hMTR4 promotes p53 protein degradation and tumor growth by accelerating rRNA processing and regulating the RPL5-MDM2 axis. Cell Death Differ 2025;32:2269-83. DOI: https://doi.org/10.1038/s41418-025-01541-4
8. Liu Y, Sun H, Li X, Liu Q, Zhao Y, Li L, et al. Identification of a three-RNA binding proteins (RBPs) signature predicting prognosis for breast cancer. Front Oncol 2021;11:663556. DOI: https://doi.org/10.3389/fonc.2021.663556
9. Xiao R, Chen JY, Liang Z, Luo D, Chen G, Lu ZJ, et al. Pervasive chromatin-RNA binding protein interactions enable RNA-based regulation of transcription. Cell 2019;178:107-21. DOI: https://doi.org/10.1016/j.cell.2019.06.001
10. Perez-Perri JI, Noerenberg M, Kamel W, Lenz CE, Mohammed S, Hentze MW, et al. Global analysis of RNA-binding protein dynamics by comparative and enhanced RNA interactome capture. Nat Protoc 2021;16:27-60. DOI: https://doi.org/10.1038/s41596-020-00404-1
11. Ma X, Li Y, Zhao B. Ribosomal protein L5 (RPL5)/ E2F transcription factor 1 (E2F1) signaling suppresses breast cancer progression via regulating endoplasmic reticulum stress and autophagy. Bioengineered 2022;13:8076-86. DOI: https://doi.org/10.1080/21655979.2022.2052672
12. Fancello L, Kampen KR, Hofman IJF, Verbeeck J, De Keersmaecker K. The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types. Oncotarget 2017;8:14462-78. DOI: https://doi.org/10.18632/oncotarget.14895
13. Ren Y, Tao C, Wang X, Ju Y. Identification of RPL5 and RPL10 as novel diagnostic biomarkers of Atypical teratoid/rhabdoid tumors. Cancer Cell Int 2018;18:190. DOI: https://doi.org/10.1186/s12935-018-0681-1
14. Ivarsdottir EV, Gudmundsson J, Tragante V, Sveinbjornsson G, Kristmundsdottir S, Stacey SN, et al. Gene-based burden tests of rare germline variants identify six cancer susceptibility genes. Nat Genet 2024;56:2422-33. DOI: https://doi.org/10.1038/s41588-024-01966-6
15. Bi G, Liang J, Bian Y, Shan G, Huang Y, Lu T, et al. Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. Nat Commun 2024;15:2461. DOI: https://doi.org/10.1038/s41467-024-46776-w
16. Hu J, Huang H, Xi Z, Ma S, Ming J, Dong F, et al. LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940/KLLN axis. Cell Death Dis 2022;13:800. DOI: https://doi.org/10.1038/s41419-022-05189-7
17. Castro-Rivera E, Ran S, Thorpe P, Minna JD. Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. P Natl Acad Sci USA 2004;101:11432-7. DOI: https://doi.org/10.1073/pnas.0403969101
18. Exposito F, Redrado M, Serrano D, Calabuig-Fariñas S, Bao-Caamano A, Gallach S, et al. G9a/DNMT1 co-targeting inhibits non-small cell lung cancer growth and reprograms tumor cells to respond to cancer-drugs through SCARA5 and AOX1. Cell Death Dis 2024;15:787. DOI: https://doi.org/10.1038/s41419-024-07156-w
19. Zhou Y, Zhang T, Wang S, Yang R, Jiao Z, Lu K, et al. Targeting of HBP1/TIMP3 axis as a novel strategy against breast cancer. Pharmacol Res 2023;194:106846. DOI: https://doi.org/10.1016/j.phrs.2023.106846
20. Worley BL, Kim YS, Mardini J, Zaman R, Leon KE, Vallur PG, et al. GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment. Redox Biol 2019;25:101051. DOI: https://doi.org/10.1016/j.redox.2018.11.009
21. Lou W, Ding B, Wang S, Fu P. Overexpression of GPX3, a potential biomarker for diagnosis and prognosis of breast cancer, inhibits progression of breast cancer cells in vitro. Cancer Cell Int 2020;20:378. DOI: https://doi.org/10.1186/s12935-020-01466-7

CRediT authorship contribution

Bing Zhao, conceptualization, funding acquisition, writing original draft preparation. Peiyuan Yu, Li Li, investigation, software, statistical analysis, reviewing and editing. Zhenhui Zhao, Xiner Zhang, reviewing and editing, methodology, supervision. All authors read and approved the final manuscript.

Supporting Agencies

National Natural Science Foundation of China , Ten-zan's High-level Talent Development Programme in Medicine and Health

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

How to Cite



1.
Zhao B, Yu P, Li L, Zhao Z, Zhang X. Histopathological evaluation of RPL5 expression in triple-negative breast cancer: an integrated immunohistochemical and transcriptomic study. Eur J Histochem [Internet]. 2026 Jul. 23 [cited 2026 Jul. 24];70(3). Available from: https://www.ejh.it/ejh/article/view/4599
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