HNSCC is one of the most common cancers. Among the salient features of this disease is the low overall survival rate of HNSCC patients despite significant advances in clinical research and new treatments (19). Accordingly, patients with the same clinical and pathological stages may show different prognosis. Recently, molecular biomarkers have shown promise in their prognostic value and have attracted increasing attention (20). Many studies have shown that mRNAs and lncRNAs can act as molecular markers to predict the outcome of HNSCC (21). Accordingly, in this study, we investigated the expression of DDX11-AS1, TMPO-AS1, and POLE gene in HNSCC due to the importance of each of the mentioned genes in the initiation and progression of cancers.
Previous studies have reported several lncRNAs, such as HOTAIR and H19, are abnormally overexpressed and associated with tumor aggressive behavior and unfavorable prognosis in HNSCC. However, the expression patterns of DDX11-AS1, TMPO-AS1, and POLE genes in human cancer remain largely unexplored (22).
Here, we measured the expression level of DDX11-AS1 in HNSCC specimens by qRT-PCR and found that its expression was higher in a large fraction of fresh HNSCC tissue compared with its paired adjacent nontumor tissue. But, this expression difference was not statistically significant. Shi et al. (2017) showed that DDX11-AS1 plays a role in DNA repair, metabolism, and cell cycle (23). On the other hand, Li et al. (2019) also showed that DDX11-AS1 exerts its oncogenic nature by suppressing Large Tumor Suppressor Kinase 2 (LATS2) gene expression, thereby increasing cell proliferation and cancer progression (24). In another study conducted by Marches et al. (2016) on colorectal cancer, they showed that the decrease in the expression of this gene leads to a decrease in cell proliferation, and arrest of the cell cycle in the G0/G1 cycle. According to all the mentioned studies and the results of this study based on increasing the expression level of this gene in tumor samples compared to normal samples, therefore, this lncRNA can be used as a potential therapeutic target in cancers (25).
Other genes examined in this study were TMPO-AS1 and POLE. Based on the results obtained from this research, TMPO-AS1 expression was not increased in tumor samples compared to normal samples. Accordingly, Yang et al. (2019) investigated the role of TMPO-AS1 in cervical cancer. The results of this study showed that the increase in the expression of TMPO-AS1 leads to a decrease in the expression level of miR 577 and as a result, an increase in the expression level of the RAB14 gene (a member of the RAS oncogene family). Finally, increasing the expression of this gene plays an important role in the development of cancer and tumorigenesis (26). Additionally, Huang et al. (2018) showed in their study that TMPO-AS1 can induce cell proliferation in prostate cancer through the effect on cell cycle and apoptosis process (27).
According to the results obtained between the expression of TMPO-AS1, DDX11-AS1, and POLE, a positive linear correlation was observed in normal samples adjacent to the tumor, which confirms the results of other studies regarding the role of these genes in similar pathways. Contrary to this, the absence of a positive linear correlation between TMPO-AS1, DDX11-AS1, and POLE mRNA in tumor samples may be due to the change in gene expression pattern by mutations, epigenetic changes or disruption in the regulatory factors of each.
In conclusion, in this study, no significant difference was observed between the expression of DDX1-AS1, TMPO-AS1, and POLE gene in tumor samples and samples adjacent to the tumor. Also, a significant positive correlation between DDX11-AS1, TMPO-AS1, and POLE gene expression was observed only in normal samples adjacent to the tumor. In this study, we showed that the investigated genetic factors such as lncRNA can play an important role as biomarkers in cancer diagnosis. Based on this, the evaluation of information related to HNSCC can lead to its initial screening and as a result reduce the death rate resulting from it. However, more studies are needed to prove this information.