PITX1 is a novel predictor of the response to chemotherapy in head and neck squamous cell carcinoma

Takenobu, Masao; Osaki, Mitsuhiko; Fujiwara, Kazunori; Fukuhara, Takahiro; Kitano, Hiroya; Kugoh, Hiroyuki; Okada, Futoshi

doi:10.3892/mco.2016.880

Cited by 13 publications

(20 citation statements)

References 31 publications

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“…Within 5kb distance of C5orf66-AS1 is pituitary homeobox 1 ( PITX1 ). PITX1 expression level was found recently to be a novel predictor for treatment response of head and neck cancer [ 44 ]. Further study is needed to see if C5orf66-AS1 could be a regulator of this neighboring PITX1 gene.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa

Houck

Lohavanichbutr

et al. 2017

Oncotarget

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Oral cavity and oropharyngeal squamous cell carcinoma (OSCC) is a major cancer type in the head and neck region. To better understand the roles long non-coding RNA (lncRNA) play in OSCC carcinogenesis, we compared the expression levels of 3,054 probe sets for lncRNAs between 167 OSCCs and 45 healthy oral mucosa using an Affymetrix HG U133 plus 2.0 array dataset. We found 658 lncRNA transcripts (790 probe sets) to be significantly differentially expressed using a criteria of FDR < 0.01, with 36 of them (39 probe sets) showing more than a 2-fold change. We further validated the top differentially expressed lncRNAs in three independent datasets from Gene Expression Omnibus (GEO) repository: GSE42743, GSE9844, and GSE6791. Fourteen lncRNAs (15 probe sets) were validated in all three datasets using the criteria FDR < 0.01: LOC441178, C5orf66-AS1, HCG22, FLG-AS1, CCL14/CCL15-CCL14, LOC100506990, TRIP10, PCBP1-AS1, LINC01315, LINC00478, COX10-AS1/LOC100506974, MLLT4-AS1, MIR31HG, and DUXAP10/LINC01296. Three lncRNAs in the validated list which showed the highest fold change (LOC441178, HCG22 and C5orf66-AS1) were verified by quantitative RT-PCR in a subset of 20 OSCCs and 10 control samples. In silico prediction of their functional role has given us directions for further investigation.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa

Houck

Lohavanichbutr

et al. 2017

Oncotarget

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“…They performed an additional in silico analysis and predicted PITX1 as target gene of lincRNA C5orf66-AS1. Interestingly, PITX1 expression is also decreased in several malignant tumors like gastric, colon and bladder cancer as well as HNSCC [ 25 , 33 , 34 ]. Reduced PITX1 expression is associated with treatment response in the latter [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, PITX1 expression is also decreased in several malignant tumors like gastric, colon and bladder cancer as well as HNSCC [ 25 , 33 , 34 ]. Reduced PITX1 expression is associated with treatment response in the latter [ 34 ]. The molecular mechanisms of the reduced expression of lincRNA C5orf66-AS1 and PITX1 in tumor tissue are incompletely understood and might be the result of epigenetic regulation.…”

Section: Introductionmentioning

confidence: 99%

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

et al. 2018

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BackgroundPatients with squamous cell cancer of the head and neck region (HNSCC) are at risk for disease recurrence and metastases, even after initial successful therapy. A tissue-based biomarker could be beneficial to guide treatment as well as post-treatment surveillance. Gene methylation status has been recently identified as powerful prognostic biomarker in HNSCC. We therefore evaluated the methylation status of the homeobox gene PITX1 and the adjacent long intergenic non-coding RNA (lincRNA) C5orf66-AS1 in publicly available datasets.MethodsGene methylation and expression data from 528 patients with HNSCC included in The Cancer Genome Atlas (TCGA, there obtained by using the Infinium HumanMethylation450 BeadChip Kit) were evaluated and methylation and expression levels of PITX1 and lincRNA C5orf66-AS1 was correlated with overall survival and other parameters. Thus, ten beads targeting PITX1 exon 3 and three beads targeting lincRNA C5orf66-AS1 were identified as significant candidates. The mean methylation of these beads was used for further correlation and the median was employed for dichotomization.ResultsBoth PITX1 exon 3 and lincRNA C5orf66-AS1 were significantly higher methylated in tumor tissue than in normal adjacent tissue (NAT) (PITX1 exon 3: tumor tissue 58.1%, NAT: 31.7%, p<0.001; lincRNA C5orf66-AS1: tumor tissue: 27.4%, NAT: 18.9%, p<0.001). In a univariate analysis, hypermethylation of both loci was significantly associated with the risk of death (univariate: exon 3: Hazard ratio (HR): 4.97 [1.78–16.71], p = 0.010, lincRNA C5orf66-AS1: Hazard ratio (HR): 12.23 [3.01–49.74], p<0.001). PITX1 exon 3 and lincRNA C5orf66-AS1 methylation was also significantly correlated with tumor localization, T category, human papilloma virus (HPV)-negative and p16-negative tumors and tumor grade. Kaplan-Meier analysis showed, that lincRNA C5orf66-AS1 hypomethylation was significantly associated with overall survival (p = 0.001) in the entire cohort as well in a subgroup of HPV-negative tumors (p = 0.003) and in patients with laryngeal tumors (p = 0.022).ConclusionMethylation status of PITX1 and even more so of lincRNA C5orf66-AS1 is a promising prognostic biomarker in HNSCC, in particular for HPV-negative patients. Further prospective evaluation is warranted.

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“…In vitro assessments showed that the overexpression of c5orf66-as1 in PAs significantly inhibits cell activity and invasiveness, indicating that this lncRNA may act as an anti-tumor agent in null cell pituitary adenomas. Using a computer algorithm, they predicted the cis-target genes of c5orf66-as1, it was found that PITX1 (pituitary homeobox 1), located in c5orf66-as within 5 kb, is a new predictor for head and neck tumors response to treatment [86]. However, further studies are needed to determine whether c5orf66-as1 can be a regulator of neighboring PITX1 genes.…”

Section: C5orf66-as1mentioning

confidence: 99%

Research Progress on lncRNA Functions and Mechanisms in Pituitary Adenomas

Yao

Wang

et al. 2020

Horm Metab Res

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Despite being the most common human neuroendocrine tumor, the pathogenesis of pituitary adenomas (PAs) is still unclear. Long non-coding RNA (lncRNA) is involved in a variety of physiological and pathological processes, and has been shown to play a key role in the process of tumor instigation and development by affecting the proliferation, migration, invasiveness, and metastasis of tumor cells. Therefore, lncRNAs may be used as diagnostic and prognostic markers of tumors. In this paper, the effect of lncRNA on the onset and progression of PAs is reviewed so as to provide a profound understanding of its pathogenesis and clinical reference for the early diagnosis of PAs.

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PITX1 is a novel predictor of the response to chemotherapy in head and neck squamous cell carcinoma

Cited by 13 publications

References 31 publications

Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa

Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

Research Progress on lncRNA Functions and Mechanisms in Pituitary Adenomas

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