Adipophilin as prognostic biomarker in clear cell renal cell carcinoma

Tolkach, Yuri; Lüders, Christine; Meller, Sebastian; Jung, Klaus; Stephan, Carsten; Kristiansen, Glen

doi:10.18632/oncotarget.15639

Cited by 20 publications

(21 citation statements)

References 41 publications

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“…The present results revealed that high PLIN2 expression was associated with good OS (P<0.001) and DFS (P=0.0006), and may be considered a diagnostic biomarker in patients with ccRCC with various clinicopathological characteristics. Three previous studies also concluded that increased PLIN2 mRNA expression is associated with a satisfactory cancer-specific survival in patients with ccRCC ( 32 , 33 , 44 ) and metastatic lesions exhibited low expression ( 32 , 44 ). Notably, the present study demonstrated that knockdown of PLIN2 promoted ccRCC cell invasion and migration in vitro .…”

Section: Discussionmentioning

confidence: 89%

“…Notably, the majority of these tumors have clear cell histology ( 30 , 31 ). Two major studies revealed the prognostic value of the transcript and protein levels of PLIN2 in ccRCC ( 32 , 33 ). Furthermore, a recent study provided evidence to suggest that PLIN2 is upregulated in ccRCC and directly proportional to hypoxia-inducible factor (HIF)2α activation ( 34 ); however, to the best of our knowledge, a functional analysis of PLIN2 in ccRCC has not yet been performed.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma

et al. 2018

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Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy in adults, the incidence of which continues to increase. The lipid droplet protein perilipin 2 (PLIN2), which was originally considered an RNA transcript, is markedly expressed during adipocyte differentiation. In addition, it has been observed to be elevated in numerous types of cancer, including ccRCC; however, its essential function remains unclear in ccRCC. The present study examined the expression of PLIN2 in ccRCC, and aimed to determine the association between PLIN2 expression and patient survival. The present study mined the transcriptional, clinicopathological and survival data of PLIN2 in patients with ccRCC through The Cancer Genome Atlas. The expression levels of PLIN2 were also detected in human ccRCC tissues and cell lines by western blotting and immunohistochemistry, and its biological role was identified by functional analysis. The results demonstrated that PLIN2 was predominantly elevated in RCC tissues and cells. In addition, the expression levels of PLIN2 were significantly associated with various clinicopathological factors, and high PLIN2 expression was associated with a good prognosis. The results of a multivariate analysis demonstrated that high PLIN2 expression was an independent prognostic indicator of overall survival (hazard ratio, 0.586; P=0.001). Furthermore, PLIN2 knockdown promoted proliferation of ccRCC cells, and enhanced cell invasion and migration. These results suggested that PLIN2 may be considered a novel prognostic factor in ccRCC and a specific diagnostic indicator for patients with ccRCC. Furthermore, it could be a potential novel target for the clinical treatment of ccRCC.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma

et al. 2018

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“…Although AQP1 is abundantly expressed in the apical membrane of proximal tubule cells, it is also known to be upregulated in lung and brain tumors . In contrast, PLIN2 is involved in lipid metabolism, transport and cellular signaling, and has been shown to be elevated in multiple malignancies that show clear cell pathology, including clear cell RCC . The exact mechanisms by which these markers are passed into the urine are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…22,23 In contrast, PLIN2 is involved in lipid metabolism, transport and cellular signaling, 24 and has been shown to be elevated in multiple malignancies that show clear cell pathology, 24,25 including clear cell RCC. 26 The exact mechanisms by which these markers are passed into the urine are unclear. Although the association of RCC with the proximal tubule provides a mechanism for these markers to be expressed in the urine, it is unclear whether they are secreted or merely shed into the urinary system.…”

Section: Discussionmentioning

confidence: 99%

Urinary aquaporin 1 and perilipin 2: Can these novel markers accurately characterize small renal masses and help guide patient management?

et al. 2018

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Objective To evaluate the role of urine aquaporin 1 and perilipin 2 as biomarkers adjunct to renal mass biopsy in guiding the management of patients with small renal masses. Methods Preoperative aquaporin 1 and perilipin 2 levels in 57 patients with small renal masses undergoing partial nephrectomy were analyzed and compared with postoperative tumor histology. An algorithm was created utilizing aquaporin 1 and perilipin 2 in conjunction with renal mass biopsy. Cut‐off values were implemented to maximize biomarker sensitivity and specificity. Renal mass biopsy utilization and intervention were then compared with rates in traditional renal mass biopsy algorithms. Results All clear cell and papillary renal cell carcinomas were correctly identified and assigned to the treatment path. All benign lesions were correctly sorted to a confirmatory renal mass biopsy path. Two chromophobe masses did not have elevated aquaporin 1 and perilipin 2, and would require renal mass biopsy. Compared with protocols that call for all small renal masses to be biopsied, confirmatory renal mass biopsy could have been safely avoided in 74% of patients with elevated aquaporin 1 and perilipin 2. Compared with protocols that do not utilize renal mass biopsy, surgical intervention would have been avoided in 23% of patients with benign masses. Conclusions Aquaporin 1 and perilipin 2 possess high sensitivity and specificity for detecting clear cell and papillary renal cell carcinoma. Use of these markers might compliment renal mass biopsy in the characterization of small renal masses.

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“…Visualization of LDs best be facilitated by the immunohistochemical expression of adipophilin, a vehicle of small LDs in non-adipogenic cells [ 8 ]. The role of adipophilin in cancer was recently investigated, and it was found to be not only a diagnostic marker, but also an independent poor prognostic marker for certain cancers, including clear cell renal cell carcinoma and brain glioma [ 9 , 10 ]. However, studies about the prognostic value of adipophilin in lung cancer were limited, and the association between the adipophilin and hypoxic ischemic pathways remains unclear.…”

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confidence: 99%

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma

Shin

Choe

et al. 2018

J Pathol Transl Med

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BackgroundThe up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.MethodsExpression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.ResultsA total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.ConclusionsActivated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

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Adipophilin as prognostic biomarker in clear cell renal cell carcinoma

Cited by 20 publications

References 41 publications

Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma

Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma

Urinary aquaporin 1 and perilipin 2: Can these novel markers accurately characterize small renal masses and help guide patient management?

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma

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