ALKBH 家族成员在非小细胞肺癌中的预后和诊断价值特征。
Characterization of the prognostic and diagnostic values of ALKBH family members in non-small cell lung cancer.
机构信息
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China; Department of Respiration, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China.
出版信息
Pathol Res Pract. 2022 Mar;231:153809. doi: 10.1016/j.prp.2022.153809. Epub 2022 Feb 12.
BACKGROUND
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).
METHODS
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).
RESULTS
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.
CONCLUSIONS
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.
背景
AlkB 同源物（ALKBH）家族基因已被证实在多种类型的癌症发展中发挥着关键作用。然而，ALKBH 家族成员在非小细胞肺癌（NSCLC）中的预后和诊断价值尚未得到系统研究。
方法
使用 ONCOMINE、UALCAN、Kaplan-Meier Plotter、cBioPortal、Metascape 和 SurvivalMeth 评估 NSCLC 中 ALKBH 家族基因的 mRNA 表达、基因组突变和生物学功能。使用免疫组织化学（IHC）分析 LUAD 组织中 ALKBH2 的表达及其与临床病理特征的相关性。
结果
ALKBH1/2/4/6 的 mRNA 水平在 NSCLC 患者中显著上调，而 ALKBH7 和 FTO 的 mRNA 水平下调。此外，ALKBH2/4/6 的高表达与总生存期（OS）、首次进展生存期（FPS）和后进展生存期（PPS）较差相关。ALKBH3/8 和 FTO 的上调与 OS、FPS 和 PPS 较好相关。ALKBH2/4/6 和 FTO 在区分 NSCLC 患者和健康个体方面具有较高的诊断价值。此外，ALKBH 家族在肺腺癌（LUAD）患者中的突变率高达 57%，并且 ALKBH 突变与 OS 不良相关。ALKBH 家族基因还参与 NSCLC 中的普遍 DNA 甲基化。最后，使用组织微阵列证实 ALKBH2 在 LUAD 中表达较高，具有较高的诊断价值。
结论
首先，我们的研究结果提供了 ALKBH 家族基因在 NSCLC 中在 DNA 和 RNA 水平上的预后和诊断价值。其次，ALKBH2 是 LUAD 的潜在新型诊断生物标志物。
Zotero 插件