ALKBH4表达在非小细胞肺癌中的临床意义

Clinical significance of ALKBH4 expression in non-small cell lung cancer.

作者信息

Aoki Masaya, Ueda Kazuhiro, Kamimura Go, Iwamoto Yoshiyuki, Ikehata Mizuki, Tabata Keisuke, Sakagami Yuri, Morizono Shoichiro, Tokunaga Takuya, Umehara Tadashi, Harada-Takeda Aya, Maeda Koki, Nagata Toshiyuki, Kariatsumari Kota, Furukawa Tatsuhiko, Tsujikawa Kazutake, Sato Masami

机构信息

Department of General Thoracic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

出版信息

Transl Cancer Res. 2022 Jul;11(7):2040-2049. doi: 10.21037/tcr-22-39.

DOI:10.21037/tcr-22-39

PMID:35966331

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9372245/

Abstract

BACKGROUND

Gene methylation is deeply involved in epigenetics and affects both the development and maintenance of homeostasis and carcinogenesis. ALKBH4 is a member of the AlkB homolog (ALKBH) family that controls demethylation of DNA and RNA.

METHODS

This study enrolled 160 patients with non-small cell lung cancer (NSCLC) who underwent complete resection. The expression of ALKBH4 in cancer tissue was evaluated by immunohistochemistry. The correlation among the expression of ALKBH4, clinicopathological factors, and prognostic outcome was evaluated.

RESULTS

In the NSCLC clinical samples, the expression of ALKBH4 was identified not only in cell membranes but also in the cytoplasm of cancer cells. In 140 of 160 cases, ALKBH4 was more highly expressed in the cancerous tissue than in the surrounding normal tissue. The proportion of cancer cells expressing ALKBH4 was higher in adenocarcinoma than in other histological types. In addition, the expression intensity of ALKBH4 in each cancer cell was also stronger in adenocarcinoma than in squamous cell carcinoma. The expression of ALKBH4 was not associated with clinicopathological factors, except for histological type. In adenocarcinoma, the recurrence-free survival (RFS) and overall survival (OS) rates were significantly lower in the ALKBH4-positive group than in the ALKBH4-negative group (P=0.008, 0.031, respectively). A multivariate logistic regression analysis indicated that the ALKBH4 expression was an independent prognostic factor for RFS (P=0.003) and OS (P=0.013). The expression of ALKBH4 was observed in all four patients with adenocarcinoma .

CONCLUSIONS

The ALKBH4 expression may be a useful predictor of the postoperative outcomes of lung adenocarcinoma (LUAD) patients.

摘要

背景

基因甲基化与表观遗传学密切相关，影响体内稳态的发展与维持以及癌症发生。ALKBH4是AlkB同源物（ALKBH）家族的成员之一，可控制DNA和RNA的去甲基化。

方法

本研究纳入了160例行根治性切除术的非小细胞肺癌（NSCLC）患者。采用免疫组织化学法评估癌组织中ALKBH4的表达。评估ALKBH4表达、临床病理因素和预后结果之间的相关性。

结果

在NSCLC临床样本中，不仅在细胞膜上，而且在癌细胞的细胞质中均检测到ALKBH4的表达。160例病例中的140例，癌组织中ALKBH4的表达高于周围正常组织。腺癌中表达ALKBH4的癌细胞比例高于其他组织学类型。此外，腺癌中每个癌细胞中ALKBH4的表达强度也高于鳞状细胞癌。除组织学类型外，ALKBH4的表达与临床病理因素无关。在腺癌中，ALKBH4阳性组的无复发生存率（RFS）和总生存率（OS）显著低于ALKBH4阴性组（分别为P = 0.008，0.031）。多因素逻辑回归分析表明，ALKBH4表达是RFS（P = 0.003）和OS（P = 0.013）的独立预后因素。在所有4例腺癌患者中均观察到ALKBH4的表达。