The Role of ISL1 and LHX5 LIM Homeobox Genes in Bladder Tumourigenesis

Abstract

Introduction: Lin-11, Isl-1 and Mec-3 domains (LIM) homeobox genes are among the most important sub-families of homeobox genes. These genes are thought to play an important role in cancer. In this study, the protein expression of these genes was examined in urothelial carcinoma of the bladder. The expression pattern of Islet-1 (ISL1) and LIM homeobox 5 (LHX5) across different cancer stages and grades, as well as the association between the protein expression of these genes and patient demographics and clinicopathological features, were examined.Methods: A total of 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues were selected from the Department of Pathology, Hospital Kuala Lumpur and the protein expression of ISL1 and LHX5 was determined using immunohistochemistry.Results: Positive expression of ISL1 and LHX5 was detected in 94% and 98% of the samples, respectively. There were no distinct LHX5 expression patterns associated with different cancer stages, but the proportion of high-expressing tumours was higher in high-grade tumours. In addition, there was a significant association between the expression of LHX5 and tumour grade. The proportion of tumours expressing high levels of ISL1 was found to be highest in later stage tumours.Conclusion: The high percentage of tumours expressing both these genes suggests that ISL1 and LHX5 play an important role in bladder tumourigenesis across multiple stages.

Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis

“…Homeobox genes contain Lin-11, Isl-1, and Mec-3 domains (LIM) subfamilies, which are involved in a series of diseases [ 20 , 32 ], including various types of cancer [ 33 ]. LHX5 , a vital member of the LIM family, has been reported to be involved in the regulation of neuronal differentiation and migration during development of the central nervous system [ 34 ].…”

“…LHX5 also has the potential to promote nerve precursor cell proliferation, neuronal differentiation, and migration during development of the hippocampus [ 34 ]. Dysregulated LHX5 has also been observed in urothelial carcinoma of the bladder [ 33 ]. TLX1 , a key member of the HOX gene family, was first identified in the T-lineage leukemia cells.…”

Identification of a Prognostic Signature Associated With the Homeobox Gene Family for Bladder Cancer

“…ISL1 plays an important role in a variety of cellular processes, including cytoskeleton genesis, organogenesis, and tumorigenesis ( Zheng and Zhao, 2007 ), and has been found to be a highly specific marker for pancreatic endocrine tumors and metastases ( Schmitt et al, 2008 ). In addition, it was also significantly associated with aggressive tumor characteristics, tumor recurrence, tumor progression, and disease-specific mortality (DSM) in BLCA and plays an important role in multiple stages of bladder tumorigenesis ( Akhir et al, 2020 ).…”

“…Current studies have shown that the homeobox gene family is aberrantly expressed in different tumors, such as bladder, bile duct, endometrial, and breast cancers ( Rao et al, 2002 ). In BLCA, ISL1 and LHX5 play important roles in multiple stages of bladder tumorigenesis ( Akhir et al, 2020 ); ZHX3 promotes migration and invasion in vitro and in vivo ( Deng et al, 2021 ). Therefore, the homeobox gene family plays an important role in the development and progression of BLCA.…”

High expression of HOXA4 in patients with glioma indicates unfavorable clinical outcomes

“…The search for a reliable biomarker for the diagnosis and prognosis of glioma is therefore of great urgency. Previous reports have confirmed that the HOX gene family plays a vital regulatory role in the evolution of cancers and is strongly associated with prognosis [ 8 , 9 ].…”