A Comparative Meta-Analysis on the Association of lncRNAs MALAT1, HOTAIR, and AFAP1-AS1 With the Risk of Developing Lymph Node Metastasis in Lung Cancer

Background: Numerous studies have demonstrated the significance of long noncoding RNA (lncRNA) in the development of cancer metastasis. The expression levels of many lncRNAs are elevated in metastatic lung cancer patients compared to non-metastatic lung cancer patients.

Objectives: The primary objective of the study was to investigate the association between the expression levels of three lncRNAs (MALAT1, HOTAIR, and AFAP1-AS1) and lymph node metastasis (LNM) of lung cancer.

Methods: Cell Press, PubMed, SpringerLink, Web of Science, and Google Scholar were explored to perform the literature search. After screening 1862 articles, 66 English-language articles were selected based on the inclusion and exclusion criteria. From those articles, 17 publications comprising 1622 lung cancer patients were chosen for statistical analyses as well as quality assessment tests.

Results: Forest plot analysis revealed that there was a significant difference in the incidence of LNM between the high and low MALAT1 expression groups (OR = 3.21, 95% CI: 1.34-7.67; random effects model). Significant differences were also observed in the incidence of LNM between patients with high and low HOTAIR expression levels (OR = 4.17, 95% CI: 1.47-11.82; random effects model). The expression level of AFAP1-AS1 was found to be significantly associated with LNM in lung cancer (OR = 2.31, 95% CI: 1.39-3.85, random effects model). Additional analysis from GEPIA and GEO databases revealed that the expression levels of these lncRNAs vary according to the type of tumor tissue, organ of metastasis, and cancer stage. However, these databases show that the result for AFAP1-AS1 is the most aligned with the meta-analysis's findings. Furthermore, several quality assessment tests showed that the AFAP1-AS1 studies are more reliable compared to the studies of other lncRNAs.

Conclusion: This study suggested that LNM in lung cancer patients is associated mostly with an elevated AFAP1-AS1 lncRNA level among the pool of three lncRNAs analyzed. Before these results can be implemented in a clinical setting, it is essential to conduct further validation and undertake comprehensive analysis to ensure robustness and reliability.