&lt;p&gt;PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis&lt;/p&gt;

Chou, Chia-Lin; Chen, Tzu‐Ju; Lin, Cheng-Yi; Lee, Sung‐Wei; Wang, Shih‐Chang; Chu, Shou-Sheng; Yang, Ching‐Chieh

doi:10.2147/ott.s243750

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…Taken with our results, this suggests that BSp treatment during the peripubertal period could result in less severe BC outcomes, as well as fewer metastases. Pcsk1 is over-expressed in breast and colorectal cancers, with poor prognoses being associated with this expression [55,56]. The current consensus is that Pcsk1 is important for tumorigenesis, so downregulation of this gene may be important for the anticancer effects that we observed [55].…”

Section: Discussionmentioning

confidence: 71%

Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes

Brane

Arora

Tollefsbol

2023

Cancers

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Breast cancer (BC) is a nearly ubiquitous malignancy that effects the lives of millions worldwide. Recently, nutritional prevention of BC has received increased attention due to its efficacy and ease of application. Chief among chemopreventive compounds are plant-based substances known as dietary phytochemicals. Sulforaphane (SFN), an epigenetically active phytochemical found in cruciferous vegetables, has shown promise in BC prevention. In addition, observational studies suggest that the life stage of phytochemical consumption may influence its anticancer properties. These life stages, called critical periods (CPs), are associated with rapid development and increased susceptibility to cellular damage. Puberty, a CP in which female breast tissue undergoes proliferation and differentiation, is of particular interest for later-life BC development. However, little is known about the importance of nutritional chemoprevention to CPs. We sought to address this by utilizing two estrogen receptor-negative [ER(-)] transgenic mouse models fed SFN-containing broccoli sprout extract during the critical period of puberty. We found that this treatment resulted in a significant decrease in tumor incidence and weight, as well as an increase in tumor latency. Further, we found significant alterations in the long-term expression of cancer-associated genes, including p21, p53, and BRCA2. Additionally, our transcriptomic analyses identified expressional changes in many cancer-associated genes, and bisulfite sequencing revealed that the antiproliferation-associated gene Erich4 was both hypomethylated and overexpressed in our experimental group. Our study indicates that dietary interventions during the CP of puberty may be important for later-life ER(-) BC prevention and highlights potential important genetic and epigenetic targets for treatment and study of the more deadly variants of BC.

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Section: Discussionmentioning

confidence: 71%

Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes

Brane

Arora

Tollefsbol

2023

Cancers

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“…Proprotein convertase subtilisin/kexin type 1 (PCSK1) encodes propro-tein convertase 1/3 involved in processing neuropeptide precursors in the neuroendocrine system. However, several PC1/3 knock-out mouse models have demonstrated that neuropeptides such as enkephalin participate in immune response regulation while modulating macrophage activity [38]. Prostaglandin E2 (PGE2) is a major metabolite of cyclooxygenase-2 (COX-2) in the tumor microenvironment, which is an important mediator of immune regulation [39].…”

Section: Discussionmentioning

confidence: 99%

A Risk Score Signature Consisting of Six Immune Genes Predicts Overall Survival in Patients with Lower-Grade Gliomas

Peng

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Lower-grade gliomas (LGGs) are less aggressive with a long overall survival (OS) time span. Because of individualized genomic features, a prognostic system incorporating molecular signatures can more accurately predict OS. Methods. Differential expression analysis between LGGs and normal tissues was performed using the Gene Expression Omnibus (GEO) datasets (GSE4290 and GSE12657). Immune-related differentially expressed genes (ImmPort-DEGs) were analyzed for functional enrichment. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an immune risk score signature (IRSS). We extracted information from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) to establish and validate the model. The relationship of model gene sets with immune infiltration was analyzed based on gene set variation analysis (GSVA) scores. Patients were divided into low- and high-risk groups based on the median score. The time-dependent receiver-operating characteristic (ROC) curve and the Kaplan-Meier curve were used to evaluate the model. Then, a precise prognostic nomogram was established, and its efficacy was verified. Results. A total of 18 related immune genes were identified, building a 6-gene IRSS (BMP2, F2R, FGF13, PCSK1, PRKCB, and PTGER3). DEGs were enriched in T cell and NK cell regulatory pathways. Immune infiltration analysis confirmed that the gene signature correlated with a decrease in innate immune cells. In terms of model evaluation, ROC curves at 1, 3, and 5 years showed moderate predictive ability of IRSS ( AUC = 0.930 , 0.797, and 0.728). The Cox regression analysis revealed that IRSS was an independent prognostic factor, and the nomogram model had good predictive ability ( C − index = 0.828 ). Meanwhile, the predictive power of IRSS was also confirmed in the training cohort. The Kaplan-Meier results showed that the prognosis of the high-risk group was significantly worse in all cohorts. Conclusion. IRSS may serve as a novel survival prediction tool in the classification of LGG patients.

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“…Studies have shown that PCSK1 is the gene most significantly associated with poor response to concurrent chemoradiotherapy (CCRT) in rectal cancer. Therefore, overexpression of PCSK1 is one of the risks of poor CCRT response and prognosis in rectal cancer patients (49). And PCSK1 is also over expressed in pure fibrolamellar hepatocellular carcinoma as one of neuroendocrine genes (50).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Metabolism-Related Risk Signature Associated With Clinical Prognosis in Glioblastoma Using Integrated Bioinformatic Analysis

Wang

Xue

et al. 2020

Front. Oncol.

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Altered metabolism of glucose, lipid and glutamine is a prominent hallmark of cancer cells. Currently, cell heterogeneity is believed to be the main cause of poor prognosis of glioblastoma (GBM) and is closely related to relapse caused by therapy resistance. However, the comprehensive model of genes related to glucose-, lipid-and glutamine-metabolism associated with the prognosis of GBM remains unclear, and the metabolic heterogeneity of GBM still needs to be further explored. Based on the expression profiles of 1,395 metabolism-related genes in three datasets of TCGA/CGGA/GSE, consistent cluster analysis revealed that GBM had three different metabolic status and prognostic clusters. Combining univariate Cox regression analysis and LASSO-penalized Cox regression machine learning methods, we identified a 17-metabolism-related genes risk signature associated with GBM prognosis. Kaplan-Meier analysis found that obtained signature could differentiate the prognosis of high-and low-risk patients in three datasets. Moreover, the multivariate Cox regression analysis and receiver operating characteristic curves indicated that the signature was an independent prognostic factor for GBM and had a strong predictive power. The above results were further validated in the CGGA and GSE13041 datasets, and consistent results were obtained. Gene set enrichment analysis (GSEA) suggested glycolysis gluconeogenesis and oxidative phosphorylation were significantly enriched in high-and low-risk GBM. Lastly Connectivity Map screened 54 potential compounds specific to different subgroups of GBM patients. Our study identified a novel metabolism-related gene signature, in addition the existence of three different metabolic status and two opposite biological processes in GBM were recognized, which revealed the metabolic heterogeneity of GBM. Robust metabolic subtypes and powerful risk prognostic models contributed a new perspective to the metabolic exploration of GBM.

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<p>PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis</p>

Cited by 6 publications

References 37 publications

Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes

Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes

A Risk Score Signature Consisting of Six Immune Genes Predicts Overall Survival in Patients with Lower-Grade Gliomas

Identification of a Metabolism-Related Risk Signature Associated With Clinical Prognosis in Glioblastoma Using Integrated Bioinformatic Analysis

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