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. 2021 May 25;11(6):468.
doi: 10.3390/jpm11060468.

Association of LINC00673 Genetic Variants with Progression of Oral Cancer

Shih-Chi Su  1   2   3 , Chiao-Wen Lin  4   5 , Po-Chung Ju  6   7 , Lun-Ching Chang  8 , Chun-Yi Chuang  6   9 , Yu-Fan Liu  10 , Ming-Ju Hsieh  11   12 , Shun-Fa Yang  13   14
Affiliations

Association of LINC00673 Genetic Variants with Progression of Oral Cancer

Shih-Chi Su et al. J Pers Med. .

Abstract

Oral squamous cell carcinoma (OSCC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Polymorphisms in the long intergenic noncoding RNA 673 (LINC00673) have been currently connected to the predisposition to various cancer types. The present study attempted to explore the impact of LINC00673 gene polymorphisms on the risk and progression of OSCC. Three LINC00673 single-nucleotide polymorphisms (SNPs), including rs11655237, rs9914618, and rs6501551, were evaluated in 1231 OSCCC cases and 1194 cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of OSCC between the case and control group. However, while assessing the clinicopathological parameters, patients carrying at least one minor allele of rs9914618 (GA and AA; OR, 1.286; 95% CI, 1.008-1.642; p = 0.043) were found to develop lymph node metastasis more often compared to those who are homozygous for the major allele. Further stratification analyses revealed that this genetic correlation with increased risk of lymphatic spread was further fortified in habitual betel quid chewers (OR, 1.534; 95% CI, 1.160-2.028; p = 0.003) or smokers (OR, 1.320; 95% CI, 1.013-1.721; p = 0.040). Moreover, through analyzing the dataset from The Cancer Genome Atlas (TCGA), we found that elevated LINC00673 levels were associated with the development of large tumors in patients with head and neck squamous cell carcinoma and the risk of lymphatic spread in smokers. These data demonstrate a joint effect of LINC00673 rs9914618 with betel nut chewing or smoking on the progression of oral cancer.

Keywords: long noncoding RNA; lymph node metastasis; oral squamous cell carcinoma; single-nucleotide polymorphism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
LINC00673 expression levels are associated with clinicopathological parameters in HNSCC. Correlations of increased LINC00673 expression with the clinical staging (A), tumor size (B), and lymph node metastasis (C) of HNSCC from The Cancer Genome Atlas (TCGA) database. (D) In HNSCC patients who were habitual smokers, increased LINC00673 expression levels were associated with lymphatic spread. p values are calculated with Student’s t-test.
Figure 2
Figure 2
Intron structure of LINC00673 (NR_137201.2) and the features of rs9914618. (A) The intron spanning the chromosome position chr17:70,577,054 to 70,577,355 (reference genome GRCh37.p13) is shown, and the SNPs of LNC00673 are indicated by the black bars. rs9914628 is centered and marked with reference SNP ID number. The H3K4Me1, H3K4Me3, and H3K27Ac tracks exhibit the enrichment of the mono-methylation of lysine 4, trimethylation of lysine 4, and acetylation of lysine 27 of the H3 histone protein, as determined in ENCODE project. DNase clusters track indicates DNase hypersensitivity regions. Chromatin State Segmentation tracks display chromatin state segmentations by integrating ChIPseq data with a hidden Markov model for H1-hESC embryonic stem cells. The chromatin state region predicted for transcribed regions is highlighted in green. (B) Sequence of the intron 1 region. The putative NFYB binding motif (MA0502.2) is shown in bold fonts. Y indicates the position of rs9914628 and denotes C or T. (C) Motif logo of NYFB consensus sequences.
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