ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer

Jingushi, Kentaro; Aoki, Masaya; Ueda, Kazuhiro; Kogaki, Takahiro; Tanimoto, Masaya; Monoe, Yuya; Ando, Masayuki; Matsumoto, Takuya; Minami, Kentaro; Ueda, Yuko; Kitae, Kaori; Hase, Hiroaki; Nagata, Toshiyuki; Harada-Takeda, Aya; Yamamoto, Masayuki; Kawahara, Kohichi; Tabata, Kazuhiro; Furukawa, Tatsuhiko; Sato, Masami; Tsujikawa, Kazutake

doi:10.1038/s41598-021-87763-1

Cited by 15 publications

(10 citation statements)

References 63 publications

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“…Interestingly, it has been reported that the ALKBH1 mRNA and protein expression levels differ in gastric cancer (16). According to our previous study, the ALKBH4 mRNA and protein expression levels were higher in LUAD and LUSC than in normal tissues (14). The current study revealed that the expression of ALKBH4 protein was also higher in NSCLC than in normal tissues.…”

Section: Discussionsupporting

confidence: 57%

“…Pilžys et al (39) reported that the silencing of ALKBH4 markedly decreased HeLa cancer cell survival. We have previously shown that ALKBH4 promotes the progression of lung cancer via E2F1 (14), which plays an important role in cell cycle progression, senescence and apoptosis (40)(41)(42). As mentioned above, the ALKBH family is associated with the progression of various cancers by playing a multifunctional role.…”

Section: Discussionmentioning

confidence: 88%

“…O u r p r e v i o u s e x p e r i m e n t a l s t u d y s h o w e d t h e preliminary results of the ALKBH4 expression in an immunohistochemical study of selected patients with large LUAD. Therefore, the relationship among tumor size and histologic subtype (LUAD vs. LUSC), the expression of ALKBH4 protein, and the prognostic outcome remained unclear (14). In the current study, we comprehensively evaluated the ALKBH4 expression in NSCLC with a multivariate analysis without any selection criteria.…”

Section: Discussionmentioning

confidence: 99%

“…Li et al (13) demonstrated that dioxygenase ALKBH4-mediated demethylation of a monomethylated site in actin (K84me1) regulates actin-myosin interaction and actomyosindependent processes such as cytokinesis and cell migration. According to our previous experimental study with NSCLC cells, ALKBH4 was suggested to play a part in cell proliferation via the upregulation of the expression of the multifunctional oncogene E2 promoter-binding factor 1 (E2F1) (14). Unfortunately, the role of ALKBH4 in clinical characters and the prognostic outcome of NSCLC is poorly understood because the previous study analyzed selected patients with large adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

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

Aoki¹,

Ueda²,

Kamimura³

et al. 2022

Transl Cancer Res TCR

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

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Aoki¹,

Ueda²,

Kamimura³

et al. 2022

Transl Cancer Res TCR

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“…ALKBH proteins could reverse N-methylation in DNA and RNA, and play potential roles in cancers as a group [18,19]. Recently an increasing body of evidence suggested that the ALKBH family promoted tumorigenesis and might be a potential target for novel anticancer therapy [20][21][22]. There are nine members of the ALKBH family in humans.…”

Section: Discussionmentioning

confidence: 99%

ALKBH family members as novel biomarkers and prognostic factors in human breast cancer

Chen

Zhou

et al. 2022

Aging

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Breast cancer is the most common lethal carcinoma worldwide and better targeted therapies are still worthy of exploration, having had some great successes already. Abnormal expression of ALKBH members were found in various cancers, and the roles played by it were the focus of attention. The ALKBH gene family encodes nine homologous enzymes (ALKBH1-8 and FTO) to repair DNA or RNA depending on Fe2+ and α-ketoglutarate (α-KG), which is related to carcinogenesis. In this study, we applied several databases to explore the roles of ALKBHs in breast cancer. We found that ALKBH members were abnormal expression in breast cancer and associated with tumor stage and subclasses. Higher alteration rates of ALKBH family were found in breast cancer. Function enrichment revealed that several cancer-associated signal pathways were related to ALKBH family such as PI3K-Akt signaling pathway and axon guidance. Infiltration of immune cells (Eosinophiles, NK CD56bright cells, mast cells, T helper cells and so on) were strongly related to ALKBHs. Moreover, we further found that there was strong correlation between ALKBH7 and higher age, later T stage, ER/PR positive and post-menopause of breast cancer patients, and patients with higher ALKBH7 expression had shorter overall survival (OS) and post progression survival (PPS). In conclusion, our findings may provide novel insights into ALKBH-targeted therapy for breast cancer patients, and ALKBH7 may be a potential prognostic biomarker.

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ALKBH1: emerging biomarker and therapeutic target for cancer treatment

Xiao,

Fu,

et al. 2024

Discov Onc

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ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer

Cited by 15 publications

References 63 publications

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

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

ALKBH family members as novel biomarkers and prognostic factors in human breast cancer

ALKBH1: emerging biomarker and therapeutic target for cancer treatment

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