Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma

Fajković, Harun; Shariat, Shahrokh F.; Klatte, Tobias; Vartolomei, Mihai Dorin; Lucca, Ilaria; Mbeutcha, Aurélie; Rouprêt, Morgan; Briganti, Alberto; Karakiewicz, Pierre I.; Margulis, Vitaly; Rink, Michael; Remzi, Mesut; Seitz, C.; Bensalah, Karim; Mathiéu, Romain

doi:10.1007/s00345-016-1767-9

Cited by 13 publications

(13 citation statements)

References 22 publications

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“…This is consistent with the increased expression of TCA cycle genes as an indicator of better ccRCC prognosis (1). Yet, the role of TS as a favorable prognostic factor is counterintuitive as studies showed that TS promotes tumor progression in metastatic disease (49)(50)(51)(52). One explanation is that TS-altered macro-and microenvironment in normal kidney tissue may play a role promoting tumor progression, even if the tumor is more indolent.…”

Section: Discussionmentioning

confidence: 99%

Tobacco smoking induces metabolic reprogramming of renal cell carcinoma

Reigle¹,

Secic²,

Biesiada³

et al. 2021

Journal of Clinical Investigation

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Background. Clear cell renal cell carcinoma (ccRCC) is the most common histologically defined renal cancer. However, it is not a uniform disease and includes several genetic subtypes with different prognosis. ccRCC is also characterized by distinguished metabolic reprogramming. Tobacco smoking (TS) is an established risk factor for ccRCC with unknown effects on tumor pathobiology. Methods. We investigated the landscape of ccRCCs and paired normal kidney tissues (NKTs) using integrated transcriptomic, metabolomic and metallomic approaches in a cohort of never smokers (NS) and long-term current smokers (LTS) Caucasian males. Results. All three Omics domains consistently identified a distinct metabolic subtype of ccRCCs in LTS, characterized by activation of oxidative phosphorylation (OxPhos) coupled with reprogramming of the malate-aspartate shuttle and metabolism of aspartate, glutamate, glutamine and histidine. Cadmium, copper and inorganic arsenic accumulated in LTS tumors showing redistribution among intracellular pools, including relocation of copper into the cytochrome c oxidase complex. Gene expression signature based on the LTS metabolic subtype provided prognostic stratification of The Cancer Genome Atlas (TCGA) ccRCC tumors that was independent from genomic alterations. Conclusions. The work identified the TS related metabolic subtype of ccRCC with vulnerabilities that can be exploited for precision medicine approaches targeting metabolic pathways. The results provided rationale for the development of metabolic biomarkers with diagnostic and prognostic applications using evaluation of OxPhos status. The metallomic analysis revealed the role of disrupted metal homeostasis in ccRCC highlighting the importance of studying effects of metals from e-cigarettes and environmental exposures.

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Section: Discussionmentioning

confidence: 99%

Tobacco smoking induces metabolic reprogramming of renal cell carcinoma

Reigle¹,

Secic²,

Biesiada³

et al. 2021

Journal of Clinical Investigation

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“…Alternatively, smoking leads to systemic hypoxia, 5 which may contribute to aggressive prostate cancer. 6 Another possibility is increased…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Tobacco smoking is known as a preventable risk factor for the development and mortality of several genitourinary cancers such as bladder cancer, 3,4 upper tract urothelial carcinoma, 5 and renal cell carcinoma. 3,6 In contrast, the effect of tobacco consumption on the incidence of prostate cancer is still a matter of debate. 7,8 Nevertheless, the association between cigarette smoking and prostate cancer mortality seems to be robust.…”

mentioning

confidence: 99%

Association of Smoking Status With Recurrence, Metastasis, and Mortality Among Patients With Localized Prostate Cancer Undergoing Prostatectomy or Radiotherapy

et al. 2018

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“…36 Consistently, it has been shown that smoking is positively associated with the incidence and mortality of RCC, 8 and that patients with metastatic RCC who are current smokers have a higher death risk. 37 Therefore, in order to explore new therapeutic strategies for renal cancer, the molecular mechanisms of tobacco-related cancer development require further studies.…”

Section: Nanog Downregulation Reversed the Ts-induced Enhancement Omentioning

confidence: 99%

Nanog mediates tobacco smoke‐induced enhancement of renal cancer stem cell properties

Zhang

Sun

et al. 2020

Environmental Toxicology

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Nanog plays an important role in the regulation of cancer stem cells (CSCs) which participate in tumorgenesis and progression. In renal cancer, tobacco smoke (TS) is considered a major risk factor. However, the molecular mechanism by which TS induces the development of renal CSC properties remains largely unknown. In this study, we showed that the level of Nanog was elevated in renal cell carcinoma (RCC) patients with a smoking history, and that Nanog overexpression promoted the traits of CSCs in renal cancer. We further demonstrated that a 8-week exposure of TS enhanced the formation of renal tumorspheres, increased the population of CD133-positive cells, and stimulated the expression of Nanog and CSC markers. In addition, TS was found to play a role in accelerating the cell growth transition from G1 to S phase in renal CSCs. Finally, we demonstrated that the TS-induced effects in renal CSCs could be reversed through the downregulation of Nanog. Our results suggested that Nanog plays a role in mediating TS-induced renal CSC properties. This study may provide new insights into the molecular mechanism of TS-related renal tumorigenesis, which can contribute to the future development of therapeutics for renal cancer.

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Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma

Abstract: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

Cited by 13 publications

References 22 publications

Tobacco smoking induces metabolic reprogramming of renal cell carcinoma

Tobacco smoking induces metabolic reprogramming of renal cell carcinoma

Association of Smoking Status With Recurrence, Metastasis, and Mortality Among Patients With Localized Prostate Cancer Undergoing Prostatectomy or Radiotherapy

Nanog mediates tobacco smoke‐induced enhancement of renal cancer stem cell properties

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