Oral squamous cell carcinoma (OSCC) remains the leading cause of cancer-related deaths worldwide. Despite extensive research on OSCC, the pathogenesis of OSCC is not fully understood. ALKBH1 is a mammalian RNA demethylase responsible for the demethylation of N6-methyladenosine (m6A) in RNA and numerous recent studies reported that ALKBH1 plays an important role in tumorigenesis and metastasis, but the role of ALKBH1 in OSCC is largely unknown.
In this study, we investigated the genetic alterations of the ALKBH1 gene in HNSCC and their association with clinicopathological features, including survival using openly available data from The Cancer Genome Atlas (TCGA). In addition, we have sequenced the complete ALKBH1 gene in 126 OSCC patients.
We found that the genetic alterations of the ALKBH1 gene were significantly associated with clinicopathological features as well as TP53 mutation. Patients with mutation of the ALKBH1 gene had worse overall survival (OS). Truncating mutation of ALKBH1 gene predicted poor OS of OSCC patients. In addition, we identified several ALKBH1 missense mutations, including novel mutations in OSCC patients, and in silico analyses indicated that these mutations could be potentially pathogenic. Moreover, mutations in the ALKBH1 gene were also associated with nodal metastasis.
Our results suggest that ALKBH1 alterations were significantly associated with poor prognosis and may represent a new marker of prognosis in OSCC.
The authors.
Indian Council of Medical Research (Grant No. DHR-GIA, 2020-9530).
All authors have declared no conflicts of interest.