Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

Abstract

The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC.

Identification of upregulated genes in oral squamous cell carcinomas

“…This clinical evolution diversity probably occurs due to multiple steps that unchain HNSCC, in which genetic events lead to the disruption of normal pathways, followed by clonal evolution. Some genes already have their role established in carcinogenesis, although the comprehension of other combined pathways could reflect in the establishment of new drug therapies and in improvement of the treatment effectiveness . With the accumulation of large amount of human gene expression data, it is possible, and also cost‐effective, to use the already available data for identifying new tumor markers or therapeutic targets.…”

“…Some genes already have their role established in carcinogenesis, although the comprehension of other combined pathways could reflect in the establishment of new drug therapies and in improvement of the treatment effectiveness. [14][15][16] With the accumulation of large amount of human gene expression data, it is possible, and also cost-effective, to use the already available data for identifying new tumor markers or therapeutic targets. However, with the availability of data from different platforms, it is worth investigating how the expression measurements produced from different technologies should be compared and integrated if possible.…”

Engrailed-2 promotes a malignant phenotype of esophageal squamous cell carcinoma through upregulating the expression of pro-oncogenic genes

“…OCT-4 is a homeobox gene well known for its function in generating induced pluripotent stem cells (Bhartiya, 2013;Seiler et al, 2011); this gene has also been identified as an oncogene known for promoting the features of cancer stem cells (Li et al, 2017;Phiboonchaiyanan & Chanvorachote, 2017). In addition to OCT-4, an increasing body of evidence reveals that homeobox genes may participate in the promotion of various malignant phenotypes such as the proliferation, migration and invasion of cancers (Hirao et al, 2019;Miwa & Kanda, 2019;Rodini et al, 2012;Song et al, 2019). We have previously reported that HoxC6, another member of homeobox superfamily, functions as an oncogene in ESCC (Tang et al, 2019).…”

Estudo da expressão de genes relacionados à resposta inflamatória e autoimune em lesões de líquen plano oral do tipo reticular por meio de PCR-array

“…A partir dos resultados obtidos, aqueles genes com expressão alterada poderão ser futuramente utilizados como marcadores específicos para uma doença, bem como para uso de alvos terapêuticos ou no desenvolvimento de vacinas (33,34) , no entanto embora esta ferramenta seja extremamente abrangente e eficaz na identificação de uma grande quantidade de genes, este não é o ponto crítico a ser desvendado, mas sim a informação quantitativa associada com um dado perfil de expressão (34) . Sendo assim, a expressão dos genes identificados por array deve ser validada com metodologias complementares, como a RT-PCR convencional, ou ainda, em tempo real (qRT-PCR), possibilitando a quantificação dessa expressão (35) . (35) .…”

“…Sendo assim, a expressão dos genes identificados por array deve ser validada com metodologias complementares, como a RT-PCR convencional, ou ainda, em tempo real (qRT-PCR), possibilitando a quantificação dessa expressão (35) . (35) .…”