Characterization of the prognostic and diagnostic values of ALKBH family members in non-small cell lung cancer

AlkB homolog (ALKBH) family genes have been known to play a crucial role in the development of several types of cancers. Nevertheless, the prognostic and diagnostic values of ALKBH family members have not been systematically investigated in non-small cell lung cancer (NSCLC).The mRNA expression, genomic mutations, and biological functions of ALKBH family genes in NSCLC were evaluated using ONCOMINE, UALCAN, Kaplan-Meier Plotter, cBioPortal, Metascape, and SurvivalMeth. ALKBH2 expression and associated clinicopathological features were analyzed in LUAD tissues using immunohistochemistry (IHC).The mRNA levels of ALKBH1/2/4/6 were significantly upregulated in NSCLC patients, while those of ALKBH7 and FTO were downregulated. Also, a higher expression of ALKBH2/4/6 correlated with poor overall survival (OS), first-progression survival (FPS), and post-progression survival (PPS). ALKBH3/8 and FTO were upregulated and related to better OS, FPS, and PPS. ALKBH2/4/6 and FTO showed a higher diagnostic value in differentiating NSCLC patients from healthy individuals. Furthermore, the ALKBH family mutation rate was as high as 57% in lung adenocarcinoma (LUAD) patients and mutations in ALKBHs were related to poor OS. ALKBH family genes were also involved in universal DNA methylation in NSCLC. Finally, it was confirmed using tissues microarray that ALKBH2 shows a high expression and has a great diagnosis value in LUAD.Firstly, our results provided prognostic and diagnostic values of ALKBH family genes in NSCLC at both the DNA and RNA levels. Secondly, ALKBH2 is a potential novel diagnostic biomarker for LUAD.