Comprehensive analysis of clinico-pathological data reveals heterogeneous relations between atherosclerosis and cancer

Budczies, Jan; Winterfeld, Moritz von; Klauschen, Frederick; Kimmritz, Anna-Christin; Daniel, Jan‐Marcus; Warth, Arne; Endris, Volker; Denkert, Carsten; Pfeiffer, Heidi; Weichert, Wilko; Dietel, Manfred; Wittschieber, Daniel

doi:10.1136/jclinpath-2013-202148

Cited by 14 publications

(7 citation statements)

References 53 publications

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“…For each patient, a definitive structured autopsy report stating final anatomical diagnoses was established that included detailed gross and microscopic findings as well as clinicopathologic correlations including case discussion. Autopsies were performed according to established protocols and reviewed and presented by at least one board-certified pathologist as described previously [ 31 , 32 ]. Briefly, each autopsy followed a standard operating procedure including macroscopic and microscopic examination, the former comprising external inspection, initial dissection and internal examination.…”

Section: Methodsmentioning

confidence: 99%

“…Third, tumors were grouped according to the major risk factor smoking. To this end, the degree of relation to tobacco smoking was graded based on the population attributable fraction (PAF) as reported previously [ 32 , 33 ]. Specifically, tumor types with PAF ≥20% were classified as smoking-related, and cancer types with PAF <20% were classified as non-smoking-related.…”

Section: Methodsmentioning

confidence: 99%

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The landscape of metastatic progression patterns across major human cancers

et al. 2014

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The majority of patients with solid malignancies die from metastatic burden. However, our current understanding of the mechanisms and resulting patterns of dissemination is limited. Here, we analyzed patterns of metastatic progression across 16 major cancer types in a cohort of 1008 patients with metastatic cancer autopsied between 2000 and 2013 to assess cancer specific progression patterns of disease and related risk predictions. The frequency and location of metastases were evaluated in and across 1) 16 major cancers, 2) smoking- and non-smoking-related cancers and 3) adeno- and squamous cell carcinoma. Associations between primary and secondary sites were analyzed by the fractional and the relative risk methods. We detected significantly different cancer specific patterns of metastatic progression with specific relative risk profiles for secondary site involvement. Histology and smoking etiology influenced these patterns. Backward analysis showed that metastatic patterns help to predict unknown primary sites. Solid malignancies maintain a unique and recurrent organ tropism to specific secondary sites which does not appear to be strongly influenced by advances in cancer medicine as shown by comparison with previous data sets. The delineated landscape of metastatic progression patterns is a comprehensive data resource to both clinical and basic scientists which aids fostering new hypotheses for cancer research and cancer therapies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The landscape of metastatic progression patterns across major human cancers

et al. 2014

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“…For example, it was proved that increased visceral-subcutaneous fat ratio was able to predict atherosclerosis 30, 31. Interestingly, an inverse association between specific type of carcinoma and atherosclerosis has been reported 32, which made a plausible explanation from another perspective to clarify the relationship of CD36 and carcinogenesis.…”

Section: Discussionmentioning

confidence: 98%

Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients

Xu¹,

Qu²,

Wang³

et al. 2019

J. Cancer

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Objective: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients.Methods: Real-Time qPCR gene expression analysis was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test in a contingency table. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by magnetic resonance imaging (MRI) and identified at the level of the umbilicus. Pearson's correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Partial likelihood test from univariate and multivariate Cox regression analysis were developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels.Results: In the current study, CD36 mRNA was demonstrated highly expressed in ccRCC compared with normal tissues. In addition, CD36 mRNA expression was significantly increased in patients with advanced TNM stage (p=0.003, p<0.001, p<0.001), and high VAT% (p=0.004). Pearson's correlation coefficient indicated that CD36 amplification positively correlated with BMI (r=0.117, p=0.025), VAT% (r=0.465, p<0.001), while negatively associated with SAT (r=-0.296, p=0.002). Median PFS was 60 months and OS was 99 months. Meanwhile, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with hazard ratios [HR; 95% confidence interval (CI)] of 4.873 (3.300-7.196, p<0.001) and 4.610 (2.956-7.189, p<0.001). In 104 cases with available MRI scans, VAT was significantly correlated with poor PFS and OS, with HR of 2.556 (1.036-6.310, p<0.042) and 3.291 (1.034-10.477, p<0.044). A total of 100 significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, UV response, angiogenesis and transforming growth factor beta (TGF-β) signaling pathways.Conclusion: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.

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“…For example, it was proved that increased visceral-subcutaneous fat ratio was able to predict atherosclerosis [30,31]. Interestingly, an inverse association between specific type of carcinoma and atherosclerosis has been reported [32], which made a plausible explanation from another perspective to clarify the relationship of CD36 and carcinogenesis. Datasets from public online database were implemented with GSEA method.…”

Section: Discussionmentioning

confidence: 99%

Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients.

Wang

et al. 2019

JCO

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571 Background: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by MRI. Pearson’s correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Cox regression analysis were developed to address the influence of independent factors on prognostic value. Gene Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from TCGA database. Results: In the current study, we demonstrated that CD36 mRNA was highly expressed in ccRCC tissues, and was found significantly increased in patients with advanced TNM stage ( p= 0.003, p< 0.001, p< 0.001), and high VAT% ( p= 0.004). Pearson’s correlation coefficient indicated CD36 amplification positively correlated with BMI ( r= 0.117, p= 0.025), VAT% ( r= 0.465, p< 0.001), while negatively with SAT ( r= -0.296, p= 0.002). Furthermore, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with HR of 4.873 (3.300-7.196, p< 0.001) and 4.610 (2.956-7.189, p< 0.001). In 104 cases whose MRI scans were available, VAT was significantly correlated with poor PFS and OS. Significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, angiogenesis and TGF-β signaling pathways. Conclusions: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.

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Comprehensive analysis of clinico-pathological data reveals heterogeneous relations between atherosclerosis and cancer

Abstract: In conclusion, the study showed an inverse association between cancer and atherosclerosis postmortem that depends on the cancer type and suggests a possible impact of chemotherapy regimens.

Cited by 14 publications

References 53 publications

The landscape of metastatic progression patterns across major human cancers

The landscape of metastatic progression patterns across major human cancers

Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients

Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients.

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