SIRT1 Expression Is Associated with the Chemotherapy Response and Prognosis of Patients with Advanced NSCLC

Zhang, Tao; Rong, Ningning; Chen, Juan; Zou, Chengwei; Jing, Hao; Zhu, Xiaolong; Zhang, Wenlong

doi:10.1371/journal.pone.0079162

Cited by 44 publications

(57 citation statements)

References 40 publications

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“…The present study identified an association of SIRT1 overexpression with shorter OS time and poor prognostic indicators in SCC, which was consistent with the results of previous studies (4,36,45). By contrast, certain reports have found a significant association between SIRT1 overexpression and more favorable prognosis in serous carcinoma of the ovary (46) and colorectal cancer (47,48).…”

Section: A B C Dsupporting

confidence: 93%

Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

Lin¹,

Peng²

2015

Oncology Letters

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Abstract. The roles of Silent mating type information regulation 2 homolog 1 (SIRT1) and High mobility group A1 (HMGA1) in human diseases have been extensively studied separately; however, to the best of our knowledge, the current study is the first to report on their interrelationship in lung cancer. The association of SIRT1 and HMGA1 in non-small cell lung cancer (NSCLC) was investigated by evaluating their expression and prognostic significance in 260 patients with NSCLC using immunohistochemistry. SIRT1 and HMGA1 expression were found to be significantly correlated with each other (P<0.001), and both were significantly associated with clinicopathological parameters, including histological type and degree of differentiation. In squamous cell carcinoma (SCC), SIRT1 + specimens were significantly associated with shorter overall survival (OS) time (P=0.019). However, in patients with adenocarcinoma (AD), no association was identified between SIRT1 and OS. In addition, HMGA1 + specimens were significantly associated with poor differentiation (P=0.028), and were more frequent in SCC than AD (P=0.015). However, HMGA1 was not associated with OS on univariate Cox regression analysis or Kaplan-Meier analysis (both P>0.05). SIRT1/HMGA1 coexpression was significantly associated with male gender (P=0.016), and moderately and poorly differentiated histological grade (P=0.025). The findings indicate that SIRT1 and HMGA1 may have significant effects during tumor progression in NSCLC, particularly in patients with SCC, and are potentially useful as prognostic indicators for patients with NSCLC.

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Section: A B C Dsupporting

confidence: 93%

Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

Lin¹,

Peng²

2015

Oncology Letters

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“…Although most previous studies failed to discover an association between SIRT1 expression and specific histological NSCLC subtypes [17, 18, 26], our results provide new insights into the potential role of SIRT1 in carcinogenesis in a histology-dependent manner. However, we cannot exclude the possibility of selection bias, as this study was based on a retrospective analysis of cases collected at a single institution.…”

Section: Discussionmentioning

confidence: 54%

“…As all cancers begin with a small disease burden and eventually advance in stage, the tendency toward higher stages among SIRT1-negative tumors may reflect an aggressive biology and short interval from tumorigenesis to local invasion or metastasis. However, other studies have linked the aggressive biological and clinical features of NSCLC with high SIRT1 expression [17, 18]. SIRT1 can also promote apoptosis via distinct signaling pathways under dynamic regulation, despite its widely known anti-apoptotic properties [19, 20].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of DNA Repair Protein Expression in Non-Small Cell Lung Cancers Treated with Platinum-Based Chemotherapy and Subsequent Curative Lung Resection

et al. 2018

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Objective: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. Methods: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy. Results: SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers. Conclusion: Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer.

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“…Increased Sirt1 expression has been reported previously in colon, skin, breast and prostate cancer and leukemia [14,15,16,17]. However, decreased Sirt1 mRNA expression has been reported in other studies in prostate and bladder carcinoma, glioblastoma and ovarian cancer [18]. A study elucidated that Sirt1 can deactivate retinoblastoma protein by deacetylation [8].…”

Section: Discussionmentioning

confidence: 99%

“…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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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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SIRT1 Expression Is Associated with the Chemotherapy Response and Prognosis of Patients with Advanced NSCLC

Cited by 44 publications

References 40 publications

Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

Prognostic Impact of DNA Repair Protein Expression in Non-Small Cell Lung Cancers Treated with Platinum-Based Chemotherapy and Subsequent Curative Lung Resection

Sirtuin1 Expression and Correlation with Histopathological Features in Retinoblastoma

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