Autophagy-related genes are potential diagnostic and prognostic biomarkers in prostate cancer

Cheng, Yifei; Qi, Feng; Li, Lü; Qin, Zongshi; Li, Xiao; Wang, Xinwei

doi:10.21037/tau-20-498

Cited by 9 publications

(4 citation statements)

References 47 publications

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“…These genes are responsible for autophagy regulation and subsequent impact on resistance of prostate cancer to platinum-containing compounds and EGFR tyrosine kinase inhibitors. Among them, five autophagy-related genes (ARGs) including ATG9B , DNAJB1 , HSPB8 , NKX2-3 and TP63 demonstrate remarkable association with prostate cancer development [ 446 ]. Further investigation demonstrates that autophagy can also be considered as a prognostic factor in prostate cancer.…”

Section: Autophagy and Prostate Cancermentioning

confidence: 99%

“…Further studies reveal an interaction between MIR205 and NKX2-3 that determines the therapy response of prostate cancer patients [ 452 ]. Therefore, autophagy and its related genes are potential biomarkers for prostate cancer diagnosis and prognosis [ 446 , 453 , 454 ]. Figure 9 provides a schematic representation of autophagy mechanism involvement in various aspects of prostate cancer from proliferation and metastasis to therapy resistance and prognostic signature.…”

Section: Autophagy and Prostate Cancermentioning

confidence: 99%

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Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

Ashrafizadeh

Paskeh

Mirzaei

et al. 2022

J Exp Clin Cancer Res

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Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a “self-degradation” mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients. Graphical abstract

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Section: Autophagy and Prostate Cancermentioning

confidence: 99%

Section: Autophagy and Prostate Cancermentioning

confidence: 99%

Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

Ashrafizadeh

Paskeh

Mirzaei

et al. 2022

J Exp Clin Cancer Res

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“…They identified sixteen DEARGs, and seven of them were associated with PCa overall survival (OS). Moreover, clinical characteristics were associated with three prognostic genes ( NPC1, BNIP3, TP53 ): the elevated expression of NPC1 (Niemann–Pick C1 protein) and BNIP3 (BCL2 Interacting Protein 3) was dramatically associated with advanced pathological T stages; in addition, overexpression of NPC1 was significantly related to higher ISUP grades [ 46 ]. Similarly, another study conducted by Hu and colleagues has evidenced more than twenty ARGs affecting disease-free survival (DFS) related to T status, N status, and Gleason score [ 47 ].…”

Section: Autophagy and Prostate Cancermentioning

confidence: 99%

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Loizzo

Pandolfo

Rogers

et al. 2022

IJMS

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Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.

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“…In support of a possible role of autophagy in MM, it was reported that aberrant expression of autophagy-related genes is associated with cancer development [30] and that multiple activators of autophagy or specific autophagy-related genes are commonly found in cancer-associated regions [31]. Interestingly, it was also described that expression of autophagy-related genes influences the response to conventional treatments in MM [32][33][34] and, thereby, disease progression [35,36], arguing that they may be useful to predict disease risk [37]. However, despite these findings suggesting a key role of autophagy in the etiology of MM and the existence of a genetic component controlling this catalytic process in MM, so far only ULK4, ATG5, and CDKN2A polymorphisms have been suggested to have an impact on the risk of MM [38,39].…”

Section: Introductionmentioning

confidence: 98%

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization

Clavero

Sánchez-Maldonado

Macauda

et al. 2023

IJMS

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Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.

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Autophagy-related genes are potential diagnostic and prognostic biomarkers in prostate cancer

Cited by 9 publications

References 47 publications

Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization

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