Clear cell renal cell carcinoma: the value of sex-specific abdominal visceral fat measured on CT for prediction of Fuhrman nuclear grade

Hu, Zexuan; Wu, Jialiang; Lai, Shih‐Wei; Xu, Yu; Zhan, Jie; Ran, Li; Liu, Xiaoyang; Wang, Ningning; Wei, Xinhua; Jiang, Xinqing; Yang, Ruimeng

doi:10.1007/s00330-020-06747-3

Cited by 16 publications

(19 citation statements)

References 33 publications

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“…We did not detect any correlation between SFA or VFA and ccRCC T stage, whereas rVFA was an independent predictor of T stage in both males and females. This is different from the findings of Hu et al [ 13 ], who found rVFA to effectively predict high-grade ccRCC in female but not male patients. However, stage IV RCC patients were not included in their study, potentially explaining the differences between our results and their prior findings.…”

Section: Discussioncontrasting

confidence: 99%

“…It is thus important that gender be taken into account when researching the relationship between visceral fat and patient outcomes. Hu et al recently determined that relative VFA (rVFA) can be evaluated to predict a higher Fuhrman nuclear grade in females, but not males [ 13 ]. As such, sex-specific abdominal visceral fat is likely to be associated with RCC patient prognosis.…”

Section: Introductionmentioning

confidence: 99%

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The value of sex-specific abdominal visceral fat as measured via CT as a predictor of clear renal cell carcinoma T stage

et al. 2021

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Although much is known about how adipose tissue affects the development of clear cell renal carcinoma (ccRCC), little information is available for the utility of sex-specific abdominal visceral fat composition as a predictor of clear cell renal carcinoma (ccRCC) T stage. We conducted CTbased sex-specific abdominal fat measurements in ccRCC patients to assess whether VFA distribution could predict the ccRCC T stage. In total, 253 patients (182 males and 71 females) from our hospital with pathologically confirmed ccRCC (178 low T-stage and 75 high T-stage) were retrospectively reviewed for the present study. Computed tomography (CT) scans were assessed using ImageJ to differentiate between the visceral and subcutaneous fat areas (VFA and SFA), after which the relative VFA (rVFA) and total fat area (TFA) were computed. The relationships between these fat area-related variables, patient age, sex, and BMI, and ccRCC T stage were then evaluated through univariate and multivariate logistic regression analysis to clarify the association between general or sex-specific abdominal visceral fat and T stage. Following adjustment for age, males with high T stage ccRCC exhibited an increased rVFA as compared to males with low T stage ccRCC, with the same relationship being observed among females. This association between rVFA and high T stage was confirmed through both univariate and multivariate models. As thus, sexspecific visceral fat composition is a reliable independent predictor that can identify both male and female patients with high T stage ccRCC.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The value of sex-specific abdominal visceral fat as measured via CT as a predictor of clear renal cell carcinoma T stage

et al. 2021

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“…A Korean study in 200 patients with stage I-a RCC found that higher VAT was significantly associated with lower ISUP grade 18 . In contrast, one US study 7 and four Asian 10,14,16,17 studies found that higher VAT was associated with higher Fuhrman grade. We found that high SAT was associated with lower risk of high Fuhrman grade in females only.…”

Section: Discussionmentioning

confidence: 88%

Association of visceral and subcutaneous adiposity with tumor stage and Fuhrman grade in renal cell carcinoma

Maurits

Sedelaar

Aben

et al. 2022

Sci Rep

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Higher BMI has been associated with lower tumor stage and grade and improved survival in renal cell cancer (RCC). BMI cannot distinguish between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We examined associations of BMI, VAT, SAT, total adipose tissue (TAT) and relative VAT (rVAT) with tumor stage and grade in RCC patients. In a Dutch multicenter population-based historical cohort study 1039 RCC patients diagnosed between 2008 and 2012 were assessed for VAT and SAT using Computed Tomography images at L3. Sex-stratified multinomial logistic regression analyses were performed (linearly per 10-unit increase) between BMI, VAT, SAT, TAT and relative VAT (rVAT) with tumor stage and Fuhrman grade. Higher VAT, TAT and rVAT were associated with a lower risk of stage IV versus stage I in males (OR 0.93; 95%CI 0.91–0.96, OR 0.95; 95%CI 0.93–0.98, OR 0.97; 95%CI 0.96–0.99, respectively). Females showed similar associations, but only higher VAT was statistically significantly associated with reduced risk of stage IV (OR 0.95 95%CI 0.89–1.00). No associations with grade, SAT or BMI were found. In conclusion, higher VAT and TAT was associated with lower risk of stage IV RCC. This might be due to weight loss or cancer cachexia in stage IV patients.

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“…Particularly important is the role of angiogenesis, tumor promoting inflammation, and metastasis, which shows a clear pattern of GS-DSA in PAAD, KIRC, and LUAD, where some gender-specific events have already been described, as mutations [80,81], and in general, risk [82,83]. KIRC, together with HSNC and LUSC, are the cancers with the highest number of gender-specific signaling circuits, all of them showing sex-dependent differences in prognosis, mortality, and treatment response, as well as in molecular characteristics associated with them [71,[84][85][86]. It is interesting to note that some cancers, such as PAAD, LUAD, and LUSC, are highly influenced by environmental factors, and therefore the gender differences might not be of physiological origin but rather could be determined by gender-specific lifestyles.…”

Section: Discussionmentioning

confidence: 88%

Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments

Çubuk

Can

Peña‐Chilet

et al. 2020

Cells

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Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are completely unknown. Here we applied mechanistic mathematical models of signaling activity to reveal the ultimate functional consequences that gender-specific gene expression activities have over cell functionality and fate. Moreover, we also used the mechanistic modeling framework to simulate the drug interventions and unravel how drug action mechanisms are affected by gender-specific differential gene expression. Interestingly, some cancers have many biological processes significantly affected by these gender-specific differences (e.g., bladder or head and neck carcinomas), while others (e.g., glioblastoma or rectum cancer) are almost insensitive to them. We found that many of these gender-specific differences affect cancer-specific pathways or in physiological signaling pathways, also involved in cancer origin and development. Finally, mechanistic models have the potential to be used for finding alternative therapeutic interventions on the pathways targeted by the drug, which lead to similar results compensating the downstream consequences of gender-specific differences in gene expression.

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Clear cell renal cell carcinoma: the value of sex-specific abdominal visceral fat measured on CT for prediction of Fuhrman nuclear grade

Cited by 16 publications

References 33 publications

The value of sex-specific abdominal visceral fat as measured via CT as a predictor of clear renal cell carcinoma T stage

The value of sex-specific abdominal visceral fat as measured via CT as a predictor of clear renal cell carcinoma T stage

Association of visceral and subcutaneous adiposity with tumor stage and Fuhrman grade in renal cell carcinoma

Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments

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