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

Shin, Sun Ah; Na, Hee Young; Choe, Ji Young; Chung, Doohyun; Park, Soo‐Jin; Oh, Sohee; Kim, Ji Eun

doi:10.4132/jptm.2018.09.13

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…The accumulation of intracellular lipid droplets is a usual observation in ischemic tissues, such as organ infarction [7]. In cancer, hypoxic signaling usually is activated by ischemia and is related to an aggressive phenotype [7,31]. It is suggested that the coordination of the metabolic deregulation and hypoxic signaling contributed to the biological aggressiveness of lung adenocarcinoma [31].…”

Section: Discussionmentioning

confidence: 99%

“…In cancer, hypoxic signaling usually is activated by ischemia and is related to an aggressive phenotype [7,31]. It is suggested that the coordination of the metabolic deregulation and hypoxic signaling contributed to the biological aggressiveness of lung adenocarcinoma [31]. To verify these three hypotheses, further studies of the functional role of ADP in SDC is required.…”

Section: Discussionmentioning

confidence: 99%

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The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma

et al. 2020

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Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)-positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism-related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADPpositive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma

et al. 2020

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“…Adipophilin has emerged as a prognostic biomarker in different cancer types, including colorectal, lung, breast, ovarian, clear cell renal cell carcinoma, and cutaneous malignant melanoma [40][41][42][43][44][45]. UM prognostication for predicting metastatic risk and patient management, involves the combination of clinical, morphological, Adipophilin as a metabolic biomarker for uveal melanoma 213…”

Section: Discussionmentioning

confidence: 99%

Novel prognostication biomarker adipophilin reveals a metabolic shift in uveal melanoma and new therapeutic opportunities

Matareed

Maranou

Koskela

et al. 2023

The Journal of Pathology

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Metastatic uveal melanoma remains incurable at present. We previously demonstrated that loss of BAP1 gene expression in tumour cells triggers molecular mechanisms of immunosuppression in the tumour microenvironment (TME) of metastatic uveal melanoma. Adipophilin is a structural protein of lipid droplets involved in fat storage within mammalian cells, and its expression has been identified in uveal melanoma. We comprehensively evaluated adipophilin expression at the RNA (PLIN2) and protein levels of 80 patients of the GDC‐TCGA‐UM study and in a local cohort of 43 primary uveal melanoma samples respectively. PLIN2 expression is a survival prognosticator biomarker in uveal melanoma. Loss of adipophilin expression is significantly associated with monosomy 3 status and nuclear BAP1 losses in uveal melanoma tumours. Integrative transcriptomic and secretome studies show a relationship between transient loss of adipophilin expression and increased levels of tumour‐associated macrophages and hypoxia genes, suggesting PLIN2‐dependent changes in oxygen and lipid metabolism in the TME of low and high‐metastatic risk uveal melanoma. We designed four adipophilin‐based multigene signatures for uveal melanoma prognostication using a transcriptomic and secretome survival‐functional network approach. Adipophilin‐based multigene signatures were validated in BAP1‐positive and BAP1‐negative uveal melanoma cell lines using a next‐generation RNA sequencing approach. We identified existing small molecules, mostly adrenergic, retinoid, and glucocorticoid receptor agonists, MEK, and RAF inhibitors, with the potential to reverse this multigene signature expression in uveal melanoma. Some of these molecules were able to impact tumour cell viability, and carvedilol, an adrenergic receptor antagonist, restored PLIN2 levels, mimicking the expression of normoxia/lipid storage signatures and reversing the expression of hypoxia/lipolysis signatures in co‐cultures of uveal melanoma cells with human macrophages. These findings open up a new research line for understanding the lipid metabolic regulation of immune responses, with implications for therapeutic innovation in uveal melanoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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“…The included studies used quantitative real-time-polymerase chain reaction or immunohistochemistry to detect the expression level of PLIN2, and all patients were divided into high or low PLIN2 expression groups by cutoff value. In the included studies, there were 10 different malignancies: breast cancer, [34][35][36][37][38] ccRCC, 18,39,40 cutaneous malignant melanoma, 41 HB, 19 hepatocellular carcinoma, 42 highgrade serous ovarian carcinoma, 43 lung adenocarcinomas, 44,45 oral squamous cell carcinoma, 46 pancreatic ductal adenocarcinoma, 47 and salivary duct carcinoma. 48 The result of analysis of survival data from the included studies were obtained following patients for 40-300 months.…”

Section: Study Identification and Characteristicsmentioning

confidence: 99%

Prognostic and clinicopathologic significance of PLIN2 in cancers: A systematic review with meta-analysis

Luo

Quan

et al. 2023

Int J Biol Markers

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The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not completely consistent. This review followed the guidelines for systematic reviews of prognostic factors studies and was reported under the Preferred Reporting Program for Systematic Reviews and Meta-Analysis (PRISMA). We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Academia for relevant articles up to September 2, 2022, and calculated the pooled hazard ratios (HR) with 95% confidence intervals (CI) to determine the association between PLIN2 expression and the prognosis of various cancers. The meta-analysis ultimately included 17 studies. The quality of all included cohort studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and an adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to assess the certainty of the results. High expression of PLIN2 was associated with poorer overall survival (HR = 1.65; 95% CI = 1.14, 2.38; P = 0.008), metastasis-free survival (HR = 1.48; 95% CI = 1.12, 1.94; P = 0.005), progression-free survival (HR = 2.11; 95% CI = 1.55, 2.87; P < 0.0005) and recurrence-free survival/relapse-free survival (HR = 2.21; 95% CI = 1.64, 2.98; P < 0.0005) in cancers. The clinicopathological parameters of digestive system malignancies suggested that high expression of PLIN2 was notably associated with distant metastasis ( + ) (odds ratio (OR) = 3.37; 95% CI = 1.31, 8.67; P = 0.012), lymph node metastasis ( + ) (OR = 1.61; 95% CI = 1.01, 2.54; P = 0.004), and tumor stage (III–IV) (OR = 1.96; 95% CI = 1.24, 3.09; P = 0.006). In summary, overexpression of PLIN2 is significantly associated with a poor prognosis in various human cancers, especially in respiratory and digestive malignancies. Thus, PLIN2 expression may be a potential prognostic biomarker in cancer patients.

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

Cited by 6 publications

References 16 publications

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma

Novel prognostication biomarker adipophilin reveals a metabolic shift in uveal melanoma and new therapeutic opportunities

Prognostic and clinicopathologic significance of PLIN2 in cancers: A systematic review with meta-analysis

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