Expression and Clinical Significance of Novel Long Noncoding RNA Fibroblast Growth Factor 10AS and FGF10 in Colorectal Cancer

Leili Rejali; Seyed Yoosef Seyedna; Hamid Asadzadeh Aghdaei; Ehsan Nazemalhosseini Mojarad; Mehrdad Hashemi

doi:10.22074/cellj.2021.7487

Expression and Clinical Significance of Novel Long Noncoding RNA Fibroblast Growth Factor 10AS and FGF10 in Colorectal Cancer

Cell J. 2021 Nov;23(6):665-673. doi: 10.22074/cellj.2021.7487. Epub 2021 Nov 23.

Authors

Leili Rejali^{1

2}, Seyed Yoosef Seyedna¹, Hamid Asadzadeh Aghdaei², Ehsan Nazemalhosseini Mojarad³, Mehrdad Hashemi^{4

5}

Affiliations

¹ Department of Biology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran.
² Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Gastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Department of Genetics, Faculty of Advanced Science and Technology, Islamic Azad University, Tehran Medical Sciences, Tehran, Iran. Email: drhashemimehrdad@gmail.com.
⁵ Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, Islamic Azad University, Tehran Medical Sciences, Tehran, Iran.

Abstract

Objective: Colorectal cancer (CRC) imposes great health burdens worldwide. Growth factors contribute to cell growth, differentiation, angiogenesis and, most importantly, tumour formation in many types of cancers. Natural antisense transcripts (NATs) are inclusively predicted to play a major role in cancer progression. The present study aims to evaluate the relationship of fibroblast growth factor 10 (FGF10) and novel long noncoding RNA (lncRNA) antisense FGF10 (FGF10AS) expression with clinicopathologic features in CRC progression to designate a biomarker for CRC early detection.

Materials and methods: This cross-sectional study was conducted on 100 CRC tumour and parallel adjacent normal tissues. We added 30 normal cases to enhance accuracy of the test. The expression levels of FGF10 and FGF10AS were evaluated by real-time polymerase chain reaction (PCR). The findings were validated by measuring expression levels in the HT29 and SW480 cell lines. Immunohistochemistry analysis was performed systematically to evaluate FGF10 protein expression. The Mann-Whitney U test with Cox regression analysis were applied. P<0.05 were designated as significant.

Results: A significant increase in expression was observed in FGF10 (P<0.001) along with a significant decrease in FGF10AS (P<0.02) in the tumour tissues in comparison with the adjacent normal tissues. Upregulation of FGF10 and downregulation of FGF10AS expression were strongly correlated with the Tumour, Node, Metastasis (TNM) stage (P<0.007 and P<0.004), vascular invasion (P<0.03 and P<0.01), lymph invasion (P<0.02 and P<0.04), and differentiation (P<0.01 and P<0.02), respectively. Moreover, the area under the receiver operating characteristic (ROC) curve for the prognostic value of FGF10 was about 0.84 (95% confidence interval [CI]: 0.771-0.912). Linear regression analysis confirmed a negative correlation between FGF10 expression and its antisense transcript (r=-0.02).

Conclusion: The relationship between the expression levels of FGF10 and FGF10AS in tumour tissues and adjacent normal tissues indicated that sense and antisense FGF RNAs could be remarkable prognostic biomarkers for achieving effective and primitive treatment.

Keywords: Biomarker; Colorectal Cancer; Fibroblast Growth Factor 10; Long Noncoding RNA.