Potential use of HOTAIR and MALAT1 as prognostic biomarkers for cervical cancer: An application to the NHS

Large loop excision of the transformation zone (LLETZ) is a common treatment for women who display grade 3 cervical intraepithelial neoplasia (CIN3). However, 78% of women report physical side effects and 71% of women report psychological effects after treatment. Furthermore, 76% of women report feeling rushed into the decision to undergo treatment, with no other monitoring option provided, highlighting the need for a less invasive monitoring procedure to be offered to patients. Long non-coding RNAs (LncRNAs) are non-coding RNA more than 200bp that display an abundance within serum. Previous research has associated the expression levels of several lncRNAs, such as Homeobox transcript antisense RNA (HOTAIR) and Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), with the commencement and progression of cervical cancer. This systematic review and meta-analysis aimed to evaluate the prognostic significance of HOTAIR and MALAT1 within the serum and tissue of cervical cancer patients. A literature search was conducted by three independent researchers spanning four databases. Using a PICOS inclusion and exclusion criteria, six identified studies (n=826) reported on the correlation between lncRNA expression and clinicopathological features in cervical cancer. HOTAIR or MALAT1 were significantly upregulated in cervical cancer patients compared to matched healthy participants (P = <0.001). Over-expression of HOTAIR or MALAT1 was associated with increased tumour size (odds ratio [OR] = 2.01, 95% confidence interval [CI] 1.42-2.85, P = <0.0.0001) and lymph node metastasis (OR = 5.32, 95% CI 3.26-8.69, P = <0.00001). Results showed that upregulation of HOTAIR or MALAT1 was associated with poorer overall survival (OS) (HOTAIR, OR = 5.73, 95% CI 3.37-9.74, P = <0.00001; MALAT1, OR = 4.00, 95% CI 2.10-7.63, P = <0.0001). High expression of HOTAIR or MALAT1 was also associated with decreased disease-free (DFS) or recurrence-free survival (RFS) (DFS, OR = 2.72 (95% CI 1.66-4.43, P = <0.0001; RFS, OR = 4.03, 95% CI 2.26-7.19, P = <0.00001). To conclude, HOTAIR and MALAT1 demonstrate potential as biomarkers for predicting the clinical outcomes and overall prognosis of cervical cancer patients. This could be a less invasive procedure option for women, to better inform patient autonomy prior to LLETZ procedure.