Gene Expression Profiling and Clinicopathological Importance of Fer1L4 and DANCR Long Non Coding RNAs in Patients with Head and Neck Squamous Cell Carcinoma

Abstract

Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) entails a heterogeneous group of tumours that emerge from the interaction between molecular changes and environmental factors. Dysregulated long noncoding RNAs (LncRNAs) play a major part in tumourigenesis and could be used as cancer biomarkers and therapeutic aims. Aim: To evaluate the expression of two lncRNAs named Fer-1 Like Family Member 4 (Fer1L4) and differentiation antagonising non protein-coding RNA (DANCR) in tumoural tissue of HNSCCs patients in comparison to Adjacent Non cancerous Tissues (ANCTs) to appraise their diagnostic power and the relationship with clinicopathological parameters. Materials and Methods: The present case-control study was designed, in which fresh frozen cancerous tissues and ANCTs were taken from 50 sporadic HNSCC patients who were attended in Imam Khomeini and Amir Alam Hospitals (Tehran, Iran) from from January to December 2019. Real-time PCR was utilised for expression profiling of Fer1L4 and DANCR. By employing GraphPad Prism 8.0 GraphPad Software, Inc., San Diego, CA, the real-time quantitative PCR experiments(2-..Ct) method and the Mann-Whitney test were exerted to analyse the obtained data. The Receiver Operating Characteristic (ROC) curve analysis was employed for figuring out the discrimination potential of two selected lncRNAs between the subject tumour and ANCT. Results: The expression of Fer1L4 was significantly down-regulated in tumoural tissues by analogy to ANCTs (p-value <0.0001) and statistically significant associations were found between the stage and grade status of the tumour with the relative expression of this lncRNA (p-value=0.008 and p-value=0.002 for stage and grade, respectively). The findings in this study indicated that the expression of DANCR was not statistically significant different in different tumoural tissues compared with ANCTs (p-value=0.46). ROC curve unraveled that the Fer1L4 had good diagnostic power Area Under Curve (AUC) 0.9252; p-value <0.0001. The expression of DANCR and Fer1L4 was significantly, respectively, higher and lower in samples with lymph node invasion and metastasis than that of the counterpart group. Concerning Human Papillomavirus (HPV) as an important exogenous factor for the development of HNSCC, DANCR and Fer1L4 were over-expressed and underexpressed, respectively in the HPV+group in comparison to HPV-. Conclusion: This work represented that Fer1L4 could be used as a novel diagnostic biomarker for HNSCC. In addition, the statistically significant difference in the expression of Fer1L4 and DANCR in metastatic tumours demonstrated that these two lncRNAs are promising targets for therapeutic purposes.

Keywords

• biomarker
• differentiation antagonising non protein coding ribonucleic acid