P3H4 Overexpression Serves as a Prognostic Factor in Lung Adenocarcinoma

Jin, Xiangfeng; Zhou, Haiqing; Song, Jianfang; Cui, Hong; Luo, Yiren; Jiang, Haiping

doi:10.1155/2021/9971353

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Physiologically, P3H4 is a prognostic factor for lung adenocarcinoma and bladder cancer ( Li et al. , 2018 ; Jin et al. , 2021 ); it contributes to cancer invasion and growth ( Hao et al.…”

Section: Discussionmentioning

confidence: 99%

CCPG1 recognizes endoplasmic reticulum luminal proteins for selective ER-phagy

Ishii

Chino

Ode

et al. 2023

MBoC

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The endoplasmic reticulum (ER) is a major cell compartment where protein synthesis, folding and post-translational modifications occur with assistance from a wide variety of chaperones and enzymes. Quality control systems selectively eliminate abnormal proteins that accumulate inside the ER due to cellular stresses. ER-phagy, i.e., selective autophagy of the ER, is a mechanism that maintains or re-establishes cellular and ER-specific homeostasis through removal of abnormal proteins. However, how ER luminal proteins are recognized by the ER-phagy machinery remains unclear. Here, we applied the aggregation-prone protein, six-repeated islet amyloid polypeptide (6xIAPP), as a model ER-phagy substrate, and found that cell cycle progression 1 (CCPG1), which is an ER-phagy receptor, efficiently mediates its degradation via ER-phagy. We also identified prolyl 3-hydroxylase family member 4 (P3H4) as an endogenous cargo of CCPG1-dependent ER-phagy. The ER luminal region of CCPG1 contains several highly conserved regions that we refer to as cargo interaction regions (CIRs); these directly interact with specific luminal cargos for ER-phagy. Notably, 6xIAPP and P3H4 directly interact with different CIRs. These findings indicate that CCPG1 is a bispecific ER-phagy receptor for ER luminal proteins and the autophagosomal membrane that contributes to the efficient removal of aberrant ER-resident proteins through ER-phagy.

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“…Physiologically, P3H4 is a prognostic factor for lung adenocarcinoma and bladder cancer ( Li et al. , 2018 ; Jin et al. , 2021 ); it contributes to cancer invasion and growth ( Hao et al.…”

Section: Discussionmentioning

confidence: 99%

CCPG1 recognizes endoplasmic reticulum luminal proteins for selective ER-phagy

Ishii

Chino

Ode

et al. 2023

MBoC

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“…Previous studies have confirmed the potential of these genes. Overexpression of P3H4 indicated a poor prognosis in lung adenocarcinoma (31). In addition, AP2S1 was confirmed as a risk factor and was correlated with immune infiltration in triple-negative breast cancer (32).…”

Section: Discussionmentioning

confidence: 85%

Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development

et al. 2022

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BackgroundmRNA vaccines are a novel technology that provide a potential strategy for cancer treatment. However, few studies exist that are focused on the application and development of mRNA vaccines in bladder cancer (BLCA). Therefore, this study filtered candidate antigens and specific mRNA-suitable populations in BLCA via comprehensive multi-omics analysis.MethodsClinical information, follow-up information, and gene expression profiles were obtained from the TCGA and GEO databases. Somatic mutation and DNA copy number variation of BLCA were visualized by cBioPortal. Significant survival genes were analyzed by GEPIA2. TIMER was used to evaluate the connection between candidate antigens and infiltration of antigen-presenting cells. Consensus clustering analysis was performed to identify immune subtypes using the ConsensusClusterPlus package. The Monocle package was used to visualize the immune landscapes of each BLCA patient. Weighted gene co-expression network analysis (WGCNA) was used to identify key genes for mRNA vaccines.ResultsAP2S1, P3H4, and RAC3 were identified as candidate tumor-specific antigens for BLCA. Three immune subtypes were classified based on immune-related gene expression profiles. Patients with the BCS2 subtype were characterized as immune “cold” and exhibited upregulation of immunogenic cell death modulators, whereas patients with BCS1 and BCS3 were immune “hot” and had upregulation of immune checkpoints. Interestingly, patients with the BCS2 subtype had a better prognosis than other subtypes. The immune landscapes of each patient were visualized and revealed the heterogeneity within the BCS1 subtype. Finally, 13 key immune genes were identified.ConclusionsAP2S1, P3H4, and RAC3 were identified as candidate tumor-specific antigens, and patients with the BCS2 and BCS1A subtypes were identified as candidate populations for mRNA vaccines. In summary, this study provides novel insights and a theoretical basis for mRNA vaccine development in BLCA and other malignancies.

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“…The last two ECM proteins are involved in the stability of collagen intermolecular crosslinks. The expression of P3h4, which encodes a protein catalyzing the hydroxylation of lysine residues in collagen alpha chains, was reported to be a predictor of poor overall survival in both bladder [40] and lung cancer [41]. PLOD2, which provides attachment sites for carbohydrates in collagen, was also initially reviewed as a potential prognostic factor [42].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness

Pouliquen¹,

Kopecka²,

Blandin³

et al. 2023

Preprint

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Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

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P3H4 Overexpression Serves as a Prognostic Factor in Lung Adenocarcinoma

Cited by 8 publications

References 33 publications

CCPG1 recognizes endoplasmic reticulum luminal proteins for selective ER-phagy

CCPG1 recognizes endoplasmic reticulum luminal proteins for selective ER-phagy

Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development

Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness

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