Clinicopathological and prognostic value of SIRT6 in patients with solid tumors: a meta-analysis and TCGA data review

Wu, Xiaojing; Wang, Shuyuan; Zhao, Xuanzhu; Lai, Sizhen; Yuan, Zhen; Zhan, Yixiang; Zhang, Chunze; Liu, Zhaoce; Liu, Lina; Ran, Xin; Zhou, Xingyu; Yin, Xin; Liu, Xinyu; Cui, Wei; Zhang, Chunze

doi:10.1186/s12935-022-02511-3

Cited by 9 publications

(10 citation statements)

References 45 publications

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“…In addition, inhibiting SIRT6 can decrease cisplatin (DDP) resistance in NSCLC cells [ 66 ]. In particular, a recent meta-analysis involving 3 solid tumors found that reduced SIRT6 expression was shown to be associated with improved OS [ 67 ]. Second, the research methods and models are different, which may also lead to different results.…”

Section: Discussionmentioning

confidence: 99%

The histone deacetylase SIRT6 promotes glycolysis through the HIF-1α/HK2 signaling axis and induces erlotinib resistance in non-small cell lung cancer

You

Wang

et al. 2022

Apoptosis

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Erlotinib is a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Overcoming erlotinib resistance is crucial to improve the survival of advanced non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. It is also an important clinical problem that urgently needs a solution. In this study, we explored strategies to overcome erlotinib resistance from the perspective of energy metabolism. SIRT6 is a histone deacetylase. Here, we found that high expression of SIRT6 is associated with poor prognosis of lung adenocarcinoma, especially in EGFR-mutated NSCLC patients. The next cell experiment found that SIRT6 expression increased in erlotinib-resistant cells, and SIRT6 expression was negatively correlated with the sensitivity of NSCLC to erlotinib. Inhibition of SIRT6 promoted erlotinib-induced apoptosis in erlotinib-resistant cells, and glycolysis in drug-resistant cells was also inhibited. Functional studies have shown that SIRT6 increases glycolysis through the HIF-1α/HK2 signaling axis in drug-resistant cells and inhibits the sensitivity of NSCLC cells to erlotinib. In addition, the HIF-1α blocker PX478-2HCL attenuated the glycolysis and erlotinib resistance induced by SIRT6. More importantly, we confirmed the antitumor effect of SIRT6 inhibition combined with erlotinib in NSCLC-bearing mice. Our findings indicate that the cancer metabolic pathway regulated by SIRT6 may be a new target for attenuating NSCLC erlotinib resistance and has potential as a biomarker or therapeutic target to improve outcomes in NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

The histone deacetylase SIRT6 promotes glycolysis through the HIF-1α/HK2 signaling axis and induces erlotinib resistance in non-small cell lung cancer

You

Wang

et al. 2022

Apoptosis

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“…Keitaro Fukuda et al confirmed that AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma (30). Low SIRT6 expression is associated with poorer OS in gastrointestinal cancer (31). However, there are few studies on the relationship between SRC, IKBKB and tumors.…”

Section: Discussionmentioning

confidence: 99%

Analysis and Identification of Necroptosis Landscape on Therapy and Prognosis in Bladder Cancer

Zhao

Jiang

Zhang

et al. 2022

Preprint

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Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but current therapeutic strategy based on chemotherapy and immune checkpoint inhibitors (ICIs) therapy cannot meet the treatment needs, which mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy, targeted drugs, and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed necroptosis landscape on therapy and prognosis in BLCA. We firstly divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analysis. Next, we constructed a novel necroptosis related genes (NRGs) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, the accuracy of NRGsocre was also verified by external datasets. In addition, a nomogram combining NRGscore and several clinicopathological features was established to predict the BLCA patient’s OS more accurately and conveniently. We also found that NRGscore was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD1, TIGIT, and LAG3 of TME, the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRGscore has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME) and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICIs therapy, and combination therapy.

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“…Both GNLY and AIM2 have been used to predict the prognosis of bladder cancer patients ( Jiang et al, 2020 ; You et al, 2022 ). Low SIRT6 expression is associated with poorer OS in gastrointestinal cancer ( Wu X. et al, 2022 ). Wu et al (2014 ) reported a loss of expression of SIRT6 when muscle-invasive urothelial carcinoma of the bladder progresses from T2 to T4 stage, indicating more reliance on glycolysis when bladder cancer invades deeper through the bladder and into the adjacent tissues.…”

Section: Discussionmentioning

confidence: 99%

Analysis and identification of the necroptosis landscape on therapy and prognosis in bladder cancer

Zhao

Jiang²,

Zhang³

et al. 2022

Front. Genet.

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Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but the current therapeutic strategy based on chemotherapy and immune checkpoint inhibitor (ICI) therapy cannot meet the treatment needs, mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy and targeted drugs and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed the necroptosis landscape on therapy and prognosis in BLCA. We first divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analyses. Next, we constructed a novel necroptosis-related gene (NRG) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, and the accuracy of the NRG score was also verified by external datasets. In addition, a nomogram combining NRG score and several clinicopathological features was established to more accurately and conveniently predict the BLCA patient’s survival. We also found that the NRG score was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD-1, TIGIT, and LAG3 of TME, and the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRG score has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME), and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICI therapy, and combination therapy.

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Clinicopathological and prognostic value of SIRT6 in patients with solid tumors: a meta-analysis and TCGA data review

Cited by 9 publications

References 45 publications

The histone deacetylase SIRT6 promotes glycolysis through the HIF-1α/HK2 signaling axis and induces erlotinib resistance in non-small cell lung cancer

The histone deacetylase SIRT6 promotes glycolysis through the HIF-1α/HK2 signaling axis and induces erlotinib resistance in non-small cell lung cancer

Analysis and Identification of Necroptosis Landscape on Therapy and Prognosis in Bladder Cancer

Analysis and identification of the necroptosis landscape on therapy and prognosis in bladder cancer

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