Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer

Long, Gongwei; Ouyang, Wei; Zhang, Yucong; Sun, Guoliang; Gan, Jiahua; Hu, Zhiquan; Li, Heng

doi:10.3389/fmolb.2021.608369

Cited by 12 publications

(12 citation statements)

References 65 publications

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“…Interestingly, in a study of prostatic adenocarcinoma cells, increased expression of the POLM gene was reported, which is in line with the results of the current study. It has also been suggested increased expression is because of the ine ciency of the HR repair pathway (20). Also, in studies on gastric and breast cancerous tissues, an increase in the XRCC4 gene expression was reported (21,22).…”

Section: Discussionmentioning

confidence: 98%

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Rajaei

Ghameshlou

Shirkoohi

et al. 2022

Preprint

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Background: Gastritis is among the most common human diseases worldwide. Although the involvement of Helicobacter pylori infection as a class I human carcinogen for gastric cancer progression is accepted, it is not well known how gastritis progression to atrophy and stomach cancer occurs. In this case-control study, the potential link of H. pylori infection with alteration in the transcription of genes involved in DNA Damage Response pathways was investigated among the patients with gastritis. Methods: To measure the difference in relative mRNA expression level of ATM, CHEK2, TP53, DCLRE1C, POLM, XRCC4 genes between H. pylori infected and non-infected patients, gastric biopsies of 30 H. pylori infected patients with moderate chronic gastritis and 30 non-infected patients with mild chronic gastritis were analyzed. Results: Up-regulation of genes linked to non-homologous end joining (NHEJ) pathway (DCLRE1C, POLM, and XRCC) was shown in 40% (8.44 fold ±13.91), 63.33% (15.72 fold ±33.08) and 50% (9.99 fold ±21.55), respectively, and also to DDR pathway (ATM, CHEK2 and TP53) in 33% (2.42 fold ±3.17), 40% (2.86 fold ±3.61) and 50% (5.00 fold ±6.52), respectively. No correlation was detected among alteration in the transcription level of the studied genes and age or gender.Conclusion: Our results provide new data that may support the potential involvement of H. pylori infection in the activation of genes involved in DNA damage response, mainly through non-homologous end joining DNA repair system that might be linked to mutagenesis in the pre-cancerous gastric tissue.

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Section: Discussionmentioning

confidence: 98%

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Rajaei

Ghameshlou

Shirkoohi

et al. 2022

Preprint

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show abstract

“…Interestingly, in a study of prostatic adenocarcinoma cells, increased expression of the POLM gene was reported, which is in line with the results of the current study. It has also been suggested increased expression is because of the ine ciency of the HR repair pathway (19). Also, in studies on gastric and breast cancerous tissues, an increase in the XRCC4 gene expression was reported (20,21).…”

Section: Discussionmentioning

confidence: 98%

“…Thirty patients with H. pylori infection and moderate chronic gastritis were regarded as case group (Mean age of 50.10 years including 14 (46.66%) female, 16 (53.33%) Male) and the remaining 30 H. pylori negative patients who showed mild chronic gastritis patients were regarded as control group (Mean age of 47.07 years including 19 (63.33%) female(19) and 11 (36.66%) Male) .…”

mentioning

confidence: 99%

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Rajaei

Ghameshlou

Shirkoohi

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Gastritis is among the most common human diseases worldwide. Although the involvement of Helicobacter pylori infection as a class I human carcinogen for gastric cancer progression is accepted, it is not well known how gastritis progression to atrophy and stomach cancer occurs. In this case-control study, the potential link of H. pylori infection with alteration in the transcription of genes involved in DNA Damage Response pathways was investigated among the patients with gastritis. Methods: To measure the difference in relative mRNA expression level of ATM, CHEK2, TP53, DCLRE1C, POLM, XRCC4 genes between H. pylori infected and non-infected patients, gastric biopsies of 30 H. pylori infected patients with moderate chronic gastritis and 30 non-infected patients with mild chronic gastritis were analyzed. Result: Up-regulation of genes linked to non-homologous end joining (NHEJ) pathway (DCLRE1C, POLM, and XRCC) was shown in 40% (8.44 fold ±13.91), 63.33% (15.72 fold ±33.08) and 50% (9.99 fold ±21.55), respectively, and also to DDR pathway (ATM, CHEK2 and TP53) in 33% (2.42 fold ±3.17), 40% (2.86 fold ±3.61) and 50% (5.00 fold ±6.52), respectively. No correlation was detected among alteration in the transcription level of the studied genes and age or gender.Conclusion: Our results provide new data that may support the potential involvement of H. pylori infection in the activation of genes involved in DNA damage response, mainly through non-homologous end joining DNA repair system that might be linked to mutagenesis in the pre-cancerous gastric tissue.

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“…The gene BRCA2 is involved, together with BRCA1 , in DNA repair, cell cycle checkpoint regulation and transcription [ 63 ]. Several studies have identified DNA repair gene signatures as effective predictors of PC progression and outcome [ 47 , 64 ] It is currently understood that the normal protein product of BRCA2 gene is important in double-strand DNA repair by maintaining genomic integrity, and that once this gene is mutated or altered, DNA damage may not be repaired properly, likely leading to the occurrence of cancer. How DNA repair is affected by homeostatic processes involving life habits and stress responses is not sufficiently understood.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we used a priori approach to select a very specific set of genes involved in the processes detailed above. The advantage of this approach over a more traditional search for cluster of highly related genes [ 46 , 47 ] is related to the ability to look for connections with the behavioral output associated with the disease onset and progression. Therefore, the main aim of this study was to develop an innovative model based on the expression of regulatory genes associated with the stress and immune responses influencing cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Multi-Dimensional Scaling Analysis of Key Regulatory Genes in Prostate Cancer Using the TCGA Database

Boldrini

Faviana

Galli

et al. 2021

Genes

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Prostate cancer (PC) is a polygenic disease with multiple gene interactions. Therefore, a detailed analysis of its epidemiology and evaluation of risk factors can help to identify more accurate predictors of aggressive disease. We used the transcriptome data from a cohort of 243 patients from the Cancer Genome Atlas (TCGA) database. Key regulatory genes involved in proliferation activity, in the regulation of stress, and in the regulation of inflammation processes of the tumor microenvironment were selected to test a priori multi-dimensional scaling (MDS) models and create a combined score to better predict the patients’ survival and disease-free intervals. Survival was positively correlated with cortisol expression and negatively with Mini-Chromosome Maintenance 7 (MCM7) and Breast-Related Cancer Antigen2 (BRCA2) expression. The disease-free interval was negatively related to the expression of enhancer of zeste homolog 2 (EZH2), MCM7, BRCA2, and programmed cell death 1 ligand 1 (PD-L1). MDS suggested two separate pathways of activation in PC. Within these two dimensions three separate clusters emerged: (1) cortisol and brain-derived neurotrophic factor BDNF, (2) PD-L1 and cytotoxic-T-lymphocyte-associated protein 4 (CTL4); (3) and finally EZH2, MCM7, BRCA2, and c-Myc. We entered the three clusters of association shown in the MDS in several Kaplan–Meier analyses. It was found that only Cluster 3 was significantly related to the interval-disease free, indicating that patients with an overall higher activity of regulatory genes of proliferation and DNA repair had a lower probability to have a longer disease-free time. In conclusion, our data study provided initial evidence that selecting patients with a high grade of proliferation and DNA repair activity could lead to an early identification of an aggressive PC with a potentials for metastatic development.

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Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer

Cited by 12 publications

References 65 publications

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Multi-Dimensional Scaling Analysis of Key Regulatory Genes in Prostate Cancer Using the TCGA Database

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