Correction: Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies

Alinezhad, Saeid; Väänänen, Riina‐Minna; Mattsson, Jesse; Li, Yifeng; Tallgrén, Terhi; Ochoa, Natalia Tong; Bjartell, Anders; Åkerfelt, Malin; Taimen, Pekka; Boström, Peter J.; Pettersson, Kim; Nees, Matthias

doi:10.1371/journal.pone.0158255

Cited by 4 publications

(5 citation statements)

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“…In recent times, PLA2G7's high expression in various tumors has been well-documented and linked to unfavorable prognoses. [13][14][15][16][17] Additionally, Lehtinen et al identified a subset of metastatic and aggressive breast cancers that exhibit heightened PLA2G7 expression, fostering epithelial-mesenchymal transition and migration in cultured breast cancer cells. 17 Zheng et al, in their work, demonstrated that suppressing PLA2G7 expression impedes the migration and proliferation of diffuse large B-cell lymphoma cells, while enhancing apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

“…12 Recent investigations have also alluded to the potential of PLA2G7 to emerge as a promising biomarker, with diagnostic and prognostic implications, within diverse categories of malignancies. [13][14][15][16] Furthermore, it is proposed that PLA2G7 has the potential to directly regulate the proliferation and apoptosis of tumor cells. 15 17 Nonetheless, a dearth of exploration remains concerning the role of PLA2G7 within the immune microenvironment of malignancies.…”

Section: What This Study Addsmentioning

confidence: 99%

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Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma

Zhang,

Liu,

Meng

et al. 2024

J Immunother Cancer

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BackgroundHepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy.MethodsIntratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy.ResultsSingle-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7highmacrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models.ConclusionsMacrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: What This Study Addsmentioning

confidence: 99%

Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma

Zhang,

Liu,

Meng

et al. 2024

J Immunother Cancer

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“…Second-generation Hsp90 inhibitors such as onalespib (AT13387) inhibited cell proliferation in the androgen-dependent PC cell lines VCaP and 22Rv1 as well as in the androgen-independent cell line LNCaP95 [44]. Additionally, XL888, a novel, synthetic, small molecule targeting Hsp90 has also induced apoptosis in PC cell lines when combined with other Hsp90 inhibitors [61].…”

Section: Targeting Of Heat-shock Proteins In Pcmentioning

confidence: 99%

“…Targeting HSPs is, therefore, a promising future direction for researchers aiming to design and synthesize high efficacy, low toxicity inhibitors that will provide novel approaches for treating neoplastic diseases [61], including PC.…”

Section: Targeting Of Heat-shock Proteins In Pcmentioning

confidence: 99%

“…on different cancer cells, including PC. In addition, Alinezhad et al [61] were able to validate novel biomarkers including gene silencing PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D, that resulted in the reduction of tumour-cell invasion in PC3 organoid cultures in combinations of clinical, functional, and bioinformatics studies.…”

Section: Applied Bioinformatics and Prostate Cancermentioning

confidence: 99%

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Prostate cancer and therapeutic challenges

Hawsawi

Zailaie²,

Oyouni

et al. 2020

J of Biol Res-Thessaloniki

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Prostate cancer (PC) is the most prevalent type of cancer in men worldwide. In Saudi Arabia, the rate of PC is increasing annually. The sex steroid hormones androgens and their receptors have critical roles in PC development and progression. Additionally, apoptosis-related proteins such as heat-shock proteins are vital molecules in PC development. Steroid hormone-deprivation therapies remain the essential treatment for patients with metastatic PCs; however, acquired resistance to hormone deprivation and the transition to PC androgen independence is a major health obstacle. In this review, we aim to detail the roles of androgens, androgen receptors and sex steroid hormones in inducing apoptosis in PC.

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Independent Evaluation of the Respective Predictive Values for High-Grade Prostate Cancer of Clinical Information and RNA Biomarkers after Upfront MRI and Image-Guided Biopsies

Roumiguié¹,

Ploussard²,

Nogueira

et al. 2020

Cancers

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Upfront MRI is taking the lead in the diagnosis of clinically significant prostate cancer, while few image-guided biopsies (IGBs) fail to demonstrate clinically significant prostate cancer. The added value of innovative biomarkers is not confirmed in this context. We analysed SelectMDx-v2 (MDx-2) in a cohort of upfront MRI and image-guided biopsy patients. Participants included patients who received a trans-rectal elastic-fusion registration IGB on the basis of DRE, PSA, PCA3, and PCPT-2.0 risk evaluation. Pre-biopsy MRI DICOM archives were reviewed according to PI-RADS-v2. Post-massage first-void urine samples stored in the institutional registered bio-repository were commercially addressed to MDxHealth to obtain MDx-2 scores. Univariate and multivariate analyses were conducted with the detection on IGB of high-grade (ISUP 2 and higher) as the dependent variable. High-grade cancer was demonstrated in 32/117 (27.4%) patients (8/2010–8/2018). Age, prostate volume, biopsy history, MDx-2, and PI-RADS-v2 scores significantly related to the detection of high-grade cancer. MDx-2 scores and the clinical variables embedded into MDx-2 scores were analysed in multivariate analysis to complement PI-RADS-v2 scores. The two combinations outperformed PI-RADS-v2 alone (AUC-ROC 0.67 vs. 0.73 and 0.80, respectively, p < 0.05) and calibration curves confirmed an adequate prediction. Similar discrimination (C-statistics, p = 0.22) was observed in the prediction of high-grade cancer, thereby questioning the respective inputs and added values of biomarkers and clinical predictors in MDx-2 scores. Based on the results of this study, we can conclude that instruments of prediction developed for systematic prostate biopsies, including those that incorporate innovative biomarkers, must be reassessed and eventually confirmed in the context of upfront MRI and IGB.

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Correction: Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies

Cited by 4 publications

References 1 publication

Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma

Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma

Prostate cancer and therapeutic challenges

Independent Evaluation of the Respective Predictive Values for High-Grade Prostate Cancer of Clinical Information and RNA Biomarkers after Upfront MRI and Image-Guided Biopsies

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