A microRNA expression signature for the prognosis of oropharyngeal squamous cell carcinoma

Gao, Ge; Gay, Hiram A.; Chernock, Rebecca D.; Zhang, Tian R.; Luo, Jingqin; Thorstad, Wade L.; Lewis, James S.; Wang, Xiaowei

doi:10.1002/cncr.27696

Cited by 70 publications

(55 citation statements)

References 40 publications

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“…Ascertaining the origin and development of liver cancer and identification of novel targets for therapy have been the focus of recent studies regarding HCC (3)(4)(5)(6)(7). MicroRNAs (miRs) are single-stranded noncoding RNAs, containing 17-19 nucleotides, which are associated with the development and progression of tumors (8)(9)(10)(11)(12) such as oropharyngeal squamous cell carcinoma (8), non-small cell lung cancer (9), thyroid cancer (10). miR-125a has previously been reported to block the proliferation, invasion and migration of breast cancer cells (13), and was also found to be effective in preventing the invasion of ovarian cancer (14), glioma (15), lung cancer (16)(17)(18) and gastric cancer (19).…”

Section: Introductionmentioning

confidence: 99%

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

Tang

Liang

et al. 2015

Oncology Letters

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Abstract. In order to explore the regulation of the invasive ability of hepatocellular carcinoma cells and the underlying mechanism, mimics sequences of microRNA (miR)-125a (miR-125a-3p/5p) and scramble sequences (miR-125a-3p-s/5p-s) were transfected into human hepatocellular carcinoma cell lines, HCC-LM3 and HepG2, and the non-malignant epithelioid hepatic cell line QZG. To inhibit and upregulate the expression of miR-125a individually. Protein expression was detected by western blotting, and the cell proliferation and migration abilities were evaluated by soft agar colony formation and Transwell assay, respectively. It was revealed that the expression of miR-125a was downregulated in HepG2 and HCC-LM3 cells compared with that of QZG cells, and expression was markedly lower in HCC-LM3 cells than that in HepG2 cells (P<0.01). The colony formation and migration rates of the cells transfected with miR-125a-3p/5p were decreased compared with negative controls, but were increased in cells transfected with miR-125a-3p-3/5p-s (P<0.01). The protein and messenger RNA expression of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) was decreased following transfection with miR-125a-5p, whereas expression was increased compared with negative controls following transfection with miR-125a-5p-s (P<0.01). Furthermore, the proliferation and migration abilities of cells were attenuated following inhibition of the PI3K/AKT/mTOR pathway by LY294002. The results of the present study indicated that miR-125a inhibits the invasive ability of hepatocellular carcinoma cells via regulation of the PI3K/AKT/mTOR pathway.

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Section: Introductionmentioning

confidence: 99%

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

Tang

Liang

et al. 2015

Oncology Letters

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“…The results varied, with many miRs proposed to correlate with tumor HPV status or outcome, with few miRs found common between studies. Mir-9, 155 and 163b were in several studies found overexpressed in HPV-positive vs. HPV-negative OPSCC, while miR-31 and 193b were downregulated (68)(69)(70)(71)73). Also, a 25 miR signature discriminating HPV-positive vs. HPV-negative OPSCC was suggested, but few of the indicated miRs were common with other studies (67).…”

Section: Microrna Expression In Oropharyngeal Cancer In Relation To Hmentioning

confidence: 88%

“…MicroRNA (miR) expression in OPSCC has been mainly analyzed in normal tissue, HPV-positive vs. HPV-negative tumor status and to a lesser extent to outcome (67)(68)(69)(70)(71)(72)(73). The results varied, with many miRs proposed to correlate with tumor HPV status or outcome, with few miRs found common between studies.…”

Section: Microrna Expression In Oropharyngeal Cancer In Relation To Hmentioning

confidence: 99%

“…Few studies have analyzed miR expression in OPSCC in relation both to HPV and clinical outcome and these miRs differ between the studies (71)(72)(73). Overexpression of miR-142-3p, 146a, 26b was positively correlated to overall survival, while miR-31, 24, 193b was negatively correlated in a study by Gao et al (73).…”

Section: Microrna Expression In Oropharyngeal Cancer In Relation To Hmentioning

confidence: 99%

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Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Näsman

Bersani

Lindquist

et al. 2017

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Abstract. Human papillomavirus (HPV)-positive tonsillarand base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negativeIn 2007, human papillomavirus (HPV) was recognized as a risk factor for oropharyngeal squamous cell carcinoma (OPSCC) by the International Agency for Research against Cancer (IARC), besides the traditional risk factors smoking and alcohol (1-4). Concurrently, an increased incidence of OPSCC, more specifically tonsillar and base of tongue cancer (TSCC and BOTSCC, the two main HPV-positive OPSCC sites) was described in many developed countries, and found to be due to a sharp rise of HPV-positive cases (5-18). These HPV-positive tumors had a much better clinical outcome than their HPV-negative counterparts and head and neck squamous cell carcinoma (HNSCC) in general when treated with radiotherapy and surgery (1-3, 15-17, 19, 20). Treatment of HNSCC including OPSCC has, however, gradually become more intensified with induction chemotherapy or concurrent chemo-radiotherapy and sometimes the administration of Erbitux, leading to more severe side effects (16, 20, 21). This is likely unnecessary for most HPV-positive TSCC and BOTSCC patients since they generally respond well to less therapy and furthermore, intensified therapy does not improve survival of [15][16][17] 20, 22, 23). It is, therefore, important to identify patients with HPV-positive TSCC and BOTSCC eligible for less treatment or targeted therapy and efforts focus now on finding predictive and targetable markers for these patients (24-39).Here, a short background of the field and an update on recent attempts to find predictive and targetable markers with different methodologies for individualized therapy is presented. Human Papillomavirus in Tonsillar and Base of Tongue Squamous Cell Carcinoma and an Epidemic Increase of these TumorsIn 2000, an association between HPV and OPSCC and TSCC was reported, and with radiotherapy and surgery, these HPVpositive cases had much better outcome than corresponding HPV-negative cases (80% vs. 40-50% 5-year survival) (1, 2). In 2004, a similar relationship of HPV to BOTSCC, but not to mobile tongue cancer was disclosed (40). Based on 5319

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“…In a study by Gao et al, 6 miRNAs were found to significantly correlate with prognosis: miR-142-3p, miR-146a and miR-26b over-expression were associated with improved survival, while miR-31, miR-24 and miR-193b over-expression were associated with poorer patient outcome [59]. miR-451 has also been identified as significantly over-expressed in HNSCC patients without recurrent disease [55].…”

Section: Associations With Survival and Prognosismentioning

confidence: 99%

Evaluating cellular microRNA expression in human papillomavirus associated head and neck squamous cell carcinoma

Emmett¹

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Squamous cell carcinoma of mucosal head and neck sites (HNSCC) is the sixth most common cause of cancer world-wide, and is associated with a significant morbidity and mortality despite advances in therapeutic options over the past decades. HNSCC includes tumours of the oral cavity, oropharynx, larynx and hypopharynx. While there has been a decline in tumours occurring as a result of exposure to the traditional risk factors of tobacco smoking and alcohol consumption, a significant increase has been observed in the number of tumours attributed to the Human Papillomavirus (HPV). This has primarily been associated with causation of tumours in the oropharynx, however, a smaller number of tumours at other subsites are also likely to be related to the virus. Although HPV-related tumours tend to have an improved prognosis and a better response to chemo-and radiotherapy, the pathobiology underlying these differences is not yet fully understood.MiRNAs are short, non-coding single strands of RNA which regulate gene expression at the posttranscriptional level. They have been identified to be dysregulated and function as tumour suppressor or oncogenes in a number of human cancers, including head and neck cancers. MiRNAs have also been associated with prognostication including associations with recurrence of disease and diseasefree survival. As they are readily available across a range of body tissues including solid tissue, saliva, and plasma, these biomarkers have potential utility in relation to screening for disease diagnosis, recurrence or progression. Although there is an established difference between HPV-positive and negative tumours in the oropharynx clinically, the majority of studies investigating miRNA expression in HNSCC have not taken this factor into account. In the small number of studies which have examined the effect of HPV on miRNA expression in HNSCC, there is a lack of consistency in the results described.This thesis aimed to assess the difference in miRNA expression between HPV-positive and negative tumours, through use of miRNA microarray followed by validation with real-time PCR using TaqMan assays combined with a sensitive detection method (Fluidigm HD) in a larger cohort of patients. It also investigated differences in miRNA expression in association with lifestyle factors, demographics and clinical outcomes. A set of seven miRNAs was identified to be differentially expressed between HPV-positive and negative tumours in the oropharynx. No difference in miRNA expression was observed between the two tumour cohorts at other subsites in the head and neck.Differences in miRNA expression were also observed with lifestyle factors such as smoking status and alcohol consumption. Recurrence of the primary tumour and overall disease-free survival were further associated with altered miRNA expression. The findings outlined in this thesis add to the present literature regarding differences in miRNA expression between HPV-positive and negative iii tumours in the oropharynx, and provide a basis for further...

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A microRNA expression signature for the prognosis of oropharyngeal squamous cell carcinoma

Cited by 70 publications

References 40 publications

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Evaluating cellular microRNA expression in human papillomavirus associated head and neck squamous cell carcinoma

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