Sirtuin1 expression predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

Teramae, Masatomo; Fukuda, Takahiro; Wada, Takuya; Kawanishi, Masaru; Imai, Kenji; Yamauchi, M.; Yasui, Toshihiro; Sumi, Toshiyuki

doi:10.3892/mco.2014.427

Cited by 13 publications

(10 citation statements)

References 35 publications

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“…Contrary to this, Sirt1 expression was associated with a lower tumor stage in ovarian serous adenocarcinoma and oral squamous cell cancer [20,21]. In this study, Sirt1 expression did not predict the stage or any high-risk histopathological features.…”

Section: Discussioncontrasting

confidence: 48%

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Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

et al. 2015

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Background: Sirtuin1 (Sirt1) is a member of highly conserved proteins and has been implicated as a tumor promoter as well as a tumor suppressor. One of the mechanisms involves deacetylation of retinoblastoma protein, thereby inhibiting the tumor suppressor function. No study has been reported on the expression of Sirt1 in retinoblastoma. Methods: We assessed the expression of Sirt1 in sections of archived tissue blocks of enucleated and exenterated specimens of retinoblastoma patients by immunohistochemistry. The histopathological features were reviewed and correlated with the expression of Sirt1. The effect of Sirt1 expression on survival was also assessed. Results: Retrospective data of 94 patients revealed that the median age at presentation was 36 months, with a male:female ratio of 1.9:1. Fifty-one percent of the patients had International Retinoblastoma Staging System (IRSS) stage 1 disease. Of the 94 sections, 89 (95%) expressed Sirt1. Forty-eight percent of the specimens showed grade 3 staining (>75% of the cells), and the intensity was 3+ in 53%. No association between Sirt1 expression and any histopathological feature was noted. Further, Sirt1 expression did not affect the overall and progression-free survival. Conclusions: Sirt1 was expressed in most of the retinoblastoma samples. However, the degree of Sirt1 expression was not associated with any high-risk histopathological feature or survival.

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Section: Discussioncontrasting

confidence: 48%

“…Sirt1 positivity was associated with a higher tumor size and TNM stage in non-small cell lung cancer and uterine cancer patients [18,19,20]. Contrary to this, Sirt1 expression was associated with a lower tumor stage in ovarian serous adenocarcinoma and oral squamous cell cancer [20,21].…”

Section: Discussionmentioning

confidence: 99%

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

et al. 2015

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“…Understanding the role of SIRT1 in cervical cancer tumorigenesis may have both prognostic and therapeutic value. One study showed that high SIRT1 expression in locally advanced cervical cancer was associated with poor prognosis and poor therapy response [24]. Although most low grade CIN lesions regress, few cases progress to invasive carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…In gynecological tumors, elevated expression of SIRT1 was seen more frequently in malignant ovarian epithelial tumors compared to benign lesions, and was associated with chemotherapy resistance in endometrial carcinoma cell lines and lower efficacy of neoadjuvant chemotherapy in locally advanced uterine cervical cancer [23][24][25]. Also, a study performed by Allison and colleagues demonstrated that HPV16 E7 unregulated SIRT1 levels in human cervical cancer cell lines [26].…”

Section: Introductionmentioning

confidence: 99%

SIRT1 overexpression in cervical squamous intraepithelial lesions and invasive squamous cell carcinoma

Vélez-Pérez

Wang

et al. 2017

Human Pathology

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Invasive squamous cell carcinoma (SCC) of the cervix involves the progression of premalignant cervical intraepithelial neoplasia (CIN) and is associated with persistent human papillomavirus infection. Most CINs will regress, and the challenge is to identify the lesions likely to progress to invasive cancer. We evaluated Sirtuin 1 (SIRT1) expression in nonneoplastic cervix, CINs, and SCCs as a potential biomarker to predict disease progression. A total of 101 cases were selected including 29 CIN 1s, 32 CIN 2s, 16 CIN 3s, 2 microinvasive SCCs, and 22 invasive SCCs. Cervical nonneoplastic squamous epithelium showed weak positivity of SIRT1 in the basal layer. SIRT1 cytoplasmic overexpression was found in 13.8% of CIN 1s (4/29), 40.6% of CIN 2s (13/32), and 50% of CIN 3s (8/16), and it was statistically significant between CIN 1 and CIN 2/3 lesions (P=.01). All 24 cases of invasive and microinvasive SCC showed SIRT1 overexpression, with 25% (6/24) showing cytoplasmic staining only, 4.2% (1/24) showing nuclear staining only, and 70.8% (17/24) showing both nuclear and cytoplasmic staining. From CIN 1 to SCC, SIRT1 expression showed steady and statistically significant increase (CIN 1 versus CIN 2-3, P=.01; CIN 2-3 versus SCC, P=.0001). Thus, SIRT1 may serve as a potential biomarker for predicting the progression of CIN to invasive SCC.

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“…Regarding gynecologic cancer entities, the role of SIRT1 is studied in cervical cancer. Here its knockdown seems to inhibit progression of paclitaxel-resistant cells (Xia and Zhou 2018 ) and its expression seems to predict the efficacy of neoadjuvant chemotherapy (Teramae et al 2015 ). Until now, there are only few studies focusing on SIRT1 as prognostic factor in endometrial and clear cell carcinomas of the uterus.…”

Section: Discussionmentioning

confidence: 99%

Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer

Beyer

Chen

Meister

et al. 2020

Histochem Cell Biol

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Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to be important. SIRT1 is also involved in cell regulatory mechanisms and can serve as tumor promotor or suppressor. Its role in tumor biology is not clear yet. In this study, we evaluated and correlated the SIRT1 expression with patients' tumor characteristics in endometrioid and clear-cell cancer of the uterus. 65 paraffinembedded samples of patients with endometrial and clear-cell cancer of the uterus were immunohistochemically stained and SIRT1 expression was evaluated by immunoreactive score. The results were correlated to clinical and pathological tumor characteristics as well as to the expression of ARID1A and β-Catenin. The staining was significantly more intensive in uterine endometrioid carcinoma compared to uterine clear-cell carcinoma (p = 0.007). The expression of SIRT1 correlated significantly with the membranous expression of β-Catenin (p = 0.028) and ARID1A (p = 0.021). Patients with positive Sir-tuin1 expression had a significantly better progression-free survival (p = 0.042), the overall survival showed a trend towards a better prognosis (p = 0.070). SIRT1 expression seems to be associated with improved progression-free survival in uterine cancer (endometrioid and clear-cell) and is correlated to the tumor suppressors β-Catenin and ARID1A. Further studies are necessary to elucidate the role of SIRT1 in uterine and ovarian cancer and its potential as a therapeutic target.

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Sirtuin1 expression predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

Cited by 13 publications

References 35 publications

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

SIRT1 overexpression in cervical squamous intraepithelial lesions and invasive squamous cell carcinoma

Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer

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