An Insight into the Diagnostic and Prognostic Value of HOX A13's Expression in Non-muscle Invasive Bladder Cancer

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2022 Jul 19

PMID 35853090

Authors

Nouha Setti Boubaker

Aymone Gurtner

Nesrine Trabelsi

Isabella Manni

Ahlem Blel

Ahmed Saadi

Marouene Chakroun

Zeineb Naimi

Selim Zaghbib

Meriam Ksontini

Khedija Meddeb

Soumaya Rammeh

Haroun Ayed

Mohamed Chebil

Giulia Piaggio

Slah Ouerhani

Affiliations

Soon will be listed here.

Abstract

Background: Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development.

Methods: Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non-muscle-invasive bladder cancer (NMIBC) and non-tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan-Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database.

Results: HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11.

Conclusion: The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.

Citing Articles

Application of PLK1 and HOXA13 Gene Expression Levels in Urine in the Diagnosis of Non-muscle Invasive Bladder Cancer.

Valizadeh S, Taghiyar S, Vahidi S, Abazari O, Tafti M, Zavar Reza J Biochem Genet. 2024; .

PMID: 38713442 DOI: 10.1007/s10528-024-10735-3.

An insight into the diagnostic and prognostic value of HOX A13's expression in non-muscle invasive bladder cancer.

Setti Boubaker N, Gurtner A, Trabelsi N, Manni I, Blel A, Saadi A J Clin Lab Anal. 2022; 36(9):e24606.

PMID: 35853090 PMC: 9459288. DOI: 10.1002/jcla.24606.

References

Brotto D, Siena A, Barros I, Carvalho S, Muys B, Goedert L . Contributions of HOX genes to cancer hallmarks: Enrichment pathway analysis and review. Tumour Biol. 2020; 42(5):1010428320918050. DOI: 10.1177/1010428320918050. View

Liu B, Wang T, Wang H, Zhang L, Xu F, Fang R . Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer tamoxifen resistance in breast cancer. J Hematol Oncol. 2018; 11(1):26. PMC: 5824486. DOI: 10.1186/s13045-018-0577-5. View

Szklarczyk D, Gable A, Lyon D, Junge A, Wyder S, Huerta-Cepas J . STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2018; 47(D1):D607-D613. PMC: 6323986. DOI: 10.1093/nar/gky1131. View

Goux C, Vacher S, Schnitzler A, Barry Delongchamps N, Zerbib M, Peyromaure M . Assessment of prognostic implication of a panel of oncogenes in bladder cancer and identification of a 3-gene signature associated with recurrence and progression risk in non-muscle-invasive bladder cancer. Sci Rep. 2020; 10(1):16641. PMC: 7538919. DOI: 10.1038/s41598-020-73642-8. View

Cui X, Qin C, Zhang Z, Su Z, Liu X, Wang S . HOXA10 promotes cell invasion and MMP-3 expression via TGFβ2-mediated activation of the p38 MAPK pathway in pancreatic cancer cells. Dig Dis Sci. 2014; 59(7):1442-51. DOI: 10.1007/s10620-014-3033-6. View

Wen Y, Shu F, Chen Y, Chen Y, Lan Y, Duan X . The prognostic value of HOXA13 in solid tumors: A meta-analysis. Clin Chim Acta. 2018; 483:64-68. DOI: 10.1016/j.cca.2018.04.024. View

Han Y, Tu W, Wen Y, Li D, Qiu G, Tang H . Identification and validation that up-expression of HOXA13 is a novel independent prognostic marker of a worse outcome in gastric cancer based on immunohistochemistry. Med Oncol. 2013; 30(2):564. DOI: 10.1007/s12032-013-0564-1. View

Cho H, Toyokawa G, Daigo Y, Hayami S, Masuda K, Ikawa N . The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. Int J Cancer. 2011; 131(3):E179-89. DOI: 10.1002/ijc.26501. View

Girgin B, KaradaG-Alpaslan M, Kocabas F . Oncogenic and tumor suppressor function of MEIS and associated factors. Turk J Biol. 2021; 44(6):328-355. PMC: 7759197. DOI: 10.3906/biy-2006-25. View

10.

Jeong T, Oh K, Xuan Nguyen N, Kim Y, Kim M, Lee S . Evaluation of HOXB13 as a molecular marker of recurrent prostate cancer. Mol Med Rep. 2012; 5(4):901-4. PMC: 3493085. DOI: 10.3892/mmr.2012.769. View

11.

Botti G, Cillo C, De Cecio R, Malzone M, Cantile M . Paralogous HOX13 Genes in Human Cancers. Cancers (Basel). 2019; 11(5). PMC: 6562813. DOI: 10.3390/cancers11050699. View

12.

Bhatlekar S, Fields J, Boman B . HOX genes and their role in the development of human cancers. J Mol Med (Berl). 2014; 92(8):811-23. DOI: 10.1007/s00109-014-1181-y. View

13.

Kelly Z, Moller-Levet C, McGrath S, Butler-Manuel S, Madhuri T, Kierzek A . The prognostic significance of specific HOX gene expression patterns in ovarian cancer. Int J Cancer. 2016; 139(7):1608-17. DOI: 10.1002/ijc.30204. View

14.

Isharwal S, Konety B . Non-muscle invasive bladder cancer risk stratification. Indian J Urol. 2015; 31(4):289-96. PMC: 4626912. DOI: 10.4103/0970-1591.166445. View

15.

Setti Boubaker N, Gurtner A, Trabelsi N, Manni I, Blel A, Saadi A . An insight into the diagnostic and prognostic value of HOX A13's expression in non-muscle invasive bladder cancer. J Clin Lab Anal. 2022; 36(9):e24606. PMC: 9459288. DOI: 10.1002/jcla.24606. View

16.

Scott V, Morgan E, Stadler H . Genitourinary functions of Hoxa13 and Hoxd13. J Biochem. 2005; 137(6):671-6. DOI: 10.1093/jb/mvi086. View

17.

Xie Y, Ma X, Chen L, Li H, Gu L, Gao Y . MicroRNAs with prognostic significance in bladder cancer: a systematic review and meta-analysis. Sci Rep. 2017; 7(1):5619. PMC: 5514092. DOI: 10.1038/s41598-017-05801-3. View

18.

Aquino G, Franco R, Sabatino R, La Mantia E, Scognamiglio G, Collina F . Deregulation of paralogous 13 HOX genes in oral squamous cell carcinoma. Am J Cancer Res. 2015; 5(10):3042-55. PMC: 4656729. View

19.

Zhang R, Zhang T, Zhai G, Guo X, Qin Y, Gan T . Evaluation of the HOXA11 level in patients with lung squamous cancer and insights into potential molecular pathways via bioinformatics analysis. World J Surg Oncol. 2018; 16(1):109. PMC: 6006563. DOI: 10.1186/s12957-018-1375-9. View

20.

Holyoake A, OSullivan P, Pollock R, Best T, Watanabe J, Kajita Y . Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder. Clin Cancer Res. 2008; 14(3):742-9. DOI: 10.1158/1078-0432.CCR-07-1672. View