Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study

Sánchez, Alejandro; Furberg, Helena; Kuo, Fengshen; Vuong, Lynda; Ged, Yasser; Patil, Sujata; Ostrovnaya, Irina; Petruzella, Stacey; Reising, Albert; Patel, Parul; Mano, Roy; Coleman, Jonathan; Russo, Paul; Liu, Catherine H.; Dannenberg, Andrew J.; Chan, Timothy A.; Motzer, Robert J.; Voss, Martin H.; Hakimi, A. Ari

doi:10.1016/s1470-2045(19)30797-1

Cited by 134 publications

(145 citation statements)

References 47 publications

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“…The study by Hakimi confirmed a strong correlation between BMI and OS of the assessed cohort but noted a stronger correlation in the sunitinib-treated group than the pazopanib group [66]. This trend was also reported in the subsequent study by Sanchez and team [13], confirming a stronger association of BMI with sunitinib in metastatic RCC patients. Previously, a combination of atezolizumab and bevacizumab was shown to result in better clinical benefit than sunitinib in RCC patients [67].…”

Section: Targeted/immunotherapy-treated Rcc Patientssupporting

confidence: 67%

“…Recently, Sanchez and colleagues [13] exclusively studied transcriptomic signatures related to the obesity paradox in both the tumor tissue and PAT of ccRCC patients who underwent immunotherapy or surgical intervention. In general, compared to normal BMI patients, tumors from obese patients overexpressed wound healing (TGF-β, epithelial-mesenchymal transition, hedgehog, and notch), hypoxia, and angiogenesis (VEGF and DOI: 10.1159/000510245 VEGF receptor 2) signaling pathways, along with the metabolic pathways, involved in adipogenesis, glycolysis, and fatty acid metabolism.…”

Section: Tumor and Peritumoral Fat Microenvironment In Normal Bmi Vermentioning

confidence: 99%

“…The Sanchez study [13] further revealed a few interesting molecular changes within the tumor microenvironment between obese and normal weight patients in the COMPARZ (targeted therapy-treated RCC patients) cohort. Primarily, obese patients demonstrated a higher proportion of infiltrating plasmacytoid dendritic cells within their tumor microenvironment, than normal weight patients.…”

Section: Targeted/immunotherapy-treated Rcc Patientsmentioning

confidence: 99%

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Biological Support to Obesity Paradox in Renal Cell Carcinoma: A Review

2020

Urol Int

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Obesity is a proven risk factor and a debated prognostic factor in renal cell carcinoma (RCC). Termed as an "obesity paradox," the topic has churned controversies, with a few arguing of no true biological association. Suggesting otherwise, a few studies revealed adiposity-induced altered molecular and transcriptomic signatures, at both the systemic and local (tumor and peritumoral adipose tissue) levels, in RCC patients, favoring the paradox. Summarizing such studies suggests of a considerable biological support to adiposity as a promising prognostic factor in RCC patients, although much needs to be clarified before adopting it as a valuable addition to the existing prognostic model.

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Section: Targeted/immunotherapy-treated Rcc Patientssupporting

confidence: 67%

Section: Tumor and Peritumoral Fat Microenvironment In Normal Bmi Vermentioning

confidence: 99%

Section: Targeted/immunotherapy-treated Rcc Patientsmentioning

confidence: 99%

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Biological Support to Obesity Paradox in Renal Cell Carcinoma: A Review

2020

Urol Int

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“…It should be emphasized that obesity has been recognized as a major underlying factor in the pathogenesis of serious OS-related health problems, such as hyperlipidemia [7], insulin resistance [8], hypertension [9], type 2 diabetes [10], cardiovascular diseases [7] and certain types of cancer [11]. Overweight/obesity has been shown to adversely affect the condition of the oral cavity, including salivary gland function [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Dysfunction of Salivary Glands, Disturbances in Salivary Antioxidants and Increased Oxidative Damage in Saliva of Overweight and Obese Adolescents

Zalewska

Kossakowska

Taranta-Janusz

et al. 2020

JCM

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Obesity is inseparably connected with oxidative stress. This process may disturb the functioning of the oral cavity, although the effect of oxidative stress on salivary gland function and changes in the qualitative composition of saliva are still unknown. Our study is the first to evaluate salivary redox homeostasis in 40 overweight and obese adolescents and in the age- and gender-matched control group. We demonstrated strengthening of the antioxidant barrier (superoxide dismutase, catalase, peroxidase, uric acid, total antioxidant capacity (TAC)) with a simultaneous decrease in reduced glutathione concentration in saliva (non-stimulated/stimulated) in overweight and obese teenagers compared to the controls. The concentration of the products of oxidative damage to proteins (advanced glycation end products), lipids (malondialdehyde, 4-hydroxynonenal) and DNA (8-hydroxydeoxyguanosine) as well as total oxidative status were significantly higher in both non-stimulated and stimulated saliva as well as plasma of overweight and obese adolescents. Importantly, we observed more severe salivary and plasma redox alterations in obese adolescents compared to overweight individuals. In the study group, we also noted a drop in stimulated salivary secretion and a decrease in total protein content. Interestingly, dysfunction of parotid glands in overweight and obese teenagers intensified with the increase of BMI. We also showed that the measurement of salivary catalase and TAC could be used to assess the central antioxidant status of overweight and obese adolescents.

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“…2,3 Interestingly, obesity also provides an improved survival. 4 The majority of RCC subtypes are classified as clear cell renal cell carcinoma (ccRCC), which account for almost 70-75% of all RCCs. 5 Cancer-specific survival rate at 5 years for ccRCC patients is 68.9% and ccRCC has a poorer prognosis compared with other RCC such as papillary and chromophobe RCC (p < 0.001).…”

Section: Introductionmentioning

confidence: 99%