An evaluation of SOX2 and hTERC gene amplifications as screening markers in oral and oropharyngeal squamous cell carcinomas

Vokač, Nadja Kokalj; Čizmarevič, Bogdan; Zagorac, Andreja; Zagradišnik, Boris; Lanišnik, Boštjan

doi:10.1186/1755-8166-7-5

Cited by 19 publications

(18 citation statements)

References 28 publications

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“…These data were strongly consistent with previous studies focused on the expression of SEC62 [27] and SOX2 [30, 35] in healthy and cancerous tissue of the head and neck region and consistently showed an overexpression of both genes in HNSCC tissue.…”

Section: Discussionsupporting

confidence: 93%

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

et al. 2016

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Chromosome 3q26 amplification represents a frequent alteration in head and neck squamous cell carcinomas (HNSCCs). Overexpression of 3q26 encoded genes SEC62 and SOX2 was detected in various cancers, including HNSCCs, indicating their potential function as oncogenes. In our study, we elucidated the function of SEC62 and SOX2 in HNSCC patients, with a main focus on their effect on lymphatic metastasis and patient survival. We analyzed SEC62 and SOX2 expression in tissue specimens from 65 HNSCC patients and 29 patients with cervical cancer of unknown primary (CUP); a higher SEC62 and lower SOX2 expression was observed in the lymph node metastases from HNSCC patients compared with the respective primary tumor. Lymph node metastases from CUP patients showed higher SEC62 and lower SOX2 expression compared with lymph node metastases from HNSCC patients. When proceeding from the N1 to the N3 stage, SEC62 expression in the lymph node metastases showed an increase and SOX2 expression showed a decrease. Moreover, both genes showed a highly significant relevance as prognostic biomarkers, with the worst prognosis for patients with high SEC62 and low SOX2 expression levels. In functional analyses, knockdown of SEC62 resulted in an inhibition of HNSCC cell migration while, conversely, SEC62 and SOX2 overexpression stimulated cell migration. Taken together, our study showed that the expression of the 3q oncogenes SEC62 and SOX2 affects lymphatic metastasis and cell migration in HNSCC and CUP patients and has a high prognostic relevance in these diseases.

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Section: Discussionsupporting

confidence: 93%

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

et al. 2016

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“…Core protein with enzymatic activity (hTERT) and RNA matrix (hTERC) to elongate the telomeres are the two essential components of telomerase [11,12]. Recently, several publications have reported the amplification of the 3q26 chromosomal region, which harbours the hTERC gene, in precursor lesions and squamous cell carcinoma of the uterine cervix where the gain of hTERC increased with increasing severity of dysplasia [10,13,14,15,16]. Gain of hTERC has also been observed in squamous cell carcinoma of the larynx, suggesting that this marker might play an important role in tumor progression [17,18,19] .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The role of hTERC amplification in oral cancerogenesis has been postulated by different authors [10][11][12][13][14][15][16][17][18][19][22][23][24] although to date, no study based on cases having a long term follow up, was available.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The gain of hTERC signals increases during the development of squamous cell carcinomas in several organs, such as the uterine cervix, larynx, esophagus and lungs [10].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…and the gain of 1q, 3q, 8q, and 15q. The genes located on those regions have been suggested as putative cancer-associated genes that might be altered during oral carcinogenesis [10] . Stabilizing the telomeres at the end of chromosomes is one of the functions acquired by tumor cells to escape programmed cell death.…”

Section: Introductionmentioning

confidence: 99%

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Gain of hTERC: a genetic marker of malignancy in oral potentially malignant lesions

et al. 2015

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YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma

Dai

Shao

Tong³

et al. 2019

Cancer Medicine

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Background Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. Methods To identify prognostic biomarkers, we performed targeted next‐generation sequencing of 416 cancer‐related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS) was analyzed. Results TP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08‐0.77, P = .015) and progression‐free survival (PFS) (HR, 0.35; 95%CI, 0.13‐0.93, P = .030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26‐13.14, P = .019) and OS (HR, 2.78; 95%CI, 0.95‐8.17, P = .062). In a subgroup analysis, while sex and M‐stage were controlled, a much stronger negative effect of YAP1 amplification vs wild‐type in LRFS was observed (log‐rank P = .0067). Conclusion The results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored.

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An evaluation of SOX2 and hTERC gene amplifications as screening markers in oral and oropharyngeal squamous cell carcinomas

Cited by 19 publications

References 28 publications

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

Gain of hTERC: a genetic marker of malignancy in oral potentially malignant lesions

YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma

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