Diabetes Mellitus is Independently Associated with an Increased Risk of Mortality in Patients with Clear Cell Renal Cell Carcinoma

Psutka, Sarah P.; Stewart, Suzanne; Boorjian, Stephen A.; Lohse, Christine M.; Tollefson, Matthew K.; Cheville, John C.; Leibovich, Bradley C.; Thompson, R. Houston

doi:10.1016/j.juro.2014.06.014

Cited by 35 publications

(26 citation statements)

References 28 publications

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“…Recent meta-analysis suggested that DM increases risk of kidney cancer [28]. Moreover, Psutka et al [29] showed DM patients had worse cancer-specific survival and overall survival after surgery for clear cell-type RCC.…”

Section: Discussionmentioning

confidence: 99%

Risk of metastasis for T1a renal cell carcinoma

Lee

Kim

et al. 2015

World J Urol

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Section: Discussionmentioning

confidence: 99%

Risk of metastasis for T1a renal cell carcinoma

Lee

Kim

et al. 2015

World J Urol

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“…We includedclearcell,papillary,chromophobe, collecting duct, and unspecified RCC histologies and excluded oncocytoma (11). TNM stage (2010 criteria) and Fuhrman grade (1)(2)(3)(4) or differentiation (well, moderately,poorly,andundifferentiated)were obtained from pathology reports.…”

Section: Ascertainment Of Rcc and Deathmentioning

confidence: 99%

Type 2 Diabetes in Relation to the Risk of Renal Cell Carcinoma Among Men and Women in Two Large Prospective Cohort Studies

et al. 2018

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“…ccRCC is responsible for the most cancer-related deaths class accounts for 70À85% of RCC [3]. RCC is considered a metabolic disease [4À6], and obesity and atherosclerosis have been reported to be risk factors for RCC [7,8]. ccRCC is known for abnormal lipid accumulation [4] of cholesterol, cholesterol esters, and neutral lipids (triglycerides) [9].…”

Section: Introductionmentioning

confidence: 99%

MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2

et al. 2020

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A B S T R A C TBackground: Lipid accumulation has been highlighted in cancer development and progression, but the exact mechanism remains unclear in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been confirmed to participate in the pathological processes of cancers, including tumour occurrence and inhibition. However, the role and mechanism of miR-765 have not been elucidated in clear cell renal cell carcinoma (ccRCC). Methods: Using The Cancer Genome Atlas (TCGA) database and qRT-PCR, we investigated differences in miR-765 and proteolipid protein 2 (PLP2) expression, as well as their clinical relevance. To investigate the function of miR-765 and PLP2 in ccRCC, we performed in vitro and in vivo experiments to explore their biological functions in ccRCC. Findings: In this study, we showed that miR-765 was upregulated in the plasma of ccRCC patients after tumour resection. Consistently, ccRCC tissues had low expression of miR-765 when compared with corresponding non-cancerous tissues. Overexpression of miR-765 suppressed cell proliferation and metastasis in vitro and in vivo. Mechanistic studies demonstrated that PLP2 was a direct target gene of miR-765. PLP2 was highly expressed in ccRCC tissues, and high PLP2 levels were positively correlated with higher tumour stage and grade and poor prognosis. PLP2 expression was negatively correlated with the miR-765 level in patient samples. We further showed that PLP2 restrained the cell metastasis and proliferation induced by miR-765 and reduced the lipid-eliminating effects of miR-765 in renal cancer cells. Interpretation: Our findings suggest that miR-765 may function as a tumour suppressor and eliminate lipids in clear cell renal cell carcinoma by targeting PLP2. EBioMedicine journal homepage: www.elsevier.com/locate/ebiom that miR-765 inhibits osteosarcoma [23] and tongue squamous cell carcinoma [24]. Nevertheless, to the best of our knowledge, there is still no relevant research about the role of miR-765 in ccRCC. We found that the plasma level of miR-765 was upregulated after tumour resection in ccRCC patients and that ccRCC tissues had a low level of miR-765 compared with corresponding non-ccerous tissues. The present study systematically describes the function and role of miR-765 in ccRCC. Functionally, miR-765 inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, miR-765 serves as a tumour suppressor and eliminates lipids by downregulating PLP2 in ccRCC. Our findings reveal that the miR-765-PLP2 axis may be a biomarker and a therapeutic target for ccRCC. Materials and methods Patient samples and cellsThirty-six clear cell renal cell carcinoma (ccRCC) patient surgical specimens, 18 non-ccRCC (nccRCC) patient surgical specimens and 18 blood plasma samples (preoperative and operational day 7 without chemotherapy or radiotherapy for ccRCC) were obtained from

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Diabetes Mellitus is Independently Associated with an Increased Risk of Mortality in Patients with Clear Cell Renal Cell Carcinoma

Abstract: Our results suggest that diabetes mellitus is independently associated with decreased cancer specific and overall survival in patients with surgically treated clear cell renal cell carcinoma.

Cited by 35 publications

References 28 publications

Risk of metastasis for T1a renal cell carcinoma

Risk of metastasis for T1a renal cell carcinoma

Type 2 Diabetes in Relation to the Risk of Renal Cell Carcinoma Among Men and Women in Two Large Prospective Cohort Studies

MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2

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