The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-κB pathways on the efficacy and acute toxicities of radiotherapy in patients with nasopharyngeal carcinoma

Guo, Chengxian; Huang, Yu‐Ling; Yu, Jingjing; Liu, Lijuan; Gong, Xiaomeng; Min, Huang; Jiang, Chunling; Liao, Yulu; Huang, Lihua; Yang, Guoping; Li, Jingao

doi:10.18632/oncotarget.15835

Cited by 23 publications

(17 citation statements)

References 54 publications

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“…Function annotation and KEGG pathway enrichment analysis showed that these up-regulated genes were mainly involved in cell division, cell cycle, DNA replication, cell proliferation and p53 signaling pathway, while the down-regulated genes were mainly enriched in cilium movement, motile cilium assembly, Huntington's disease, inner and outer dynein arm assembly. Recent studies indicated that single nucleotide polymorphisms in genes of cell cycle pathway and NF-κB pathway can potentially predict the clinical responses to radiotherapy for NPC patients [ 11 ]. These results were consistent with the fact that cancer development and progression are closely related to the defective function of cell cycle and cell proliferation regulators.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2017

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Nasopharyngeal carcinoma is a metastatic malignant tumor originating from nasopharyngeal epithelium. Lacking or nonspecific symptoms of patients with early stage nasopharyngeal carcinoma have significantly reduced the accuracy of diagnosing and predicting nasopharyngeal carcinoma development. This study aimed to identify gene signatures of nasopharyngeal carcinoma and uncover potential mechanisms. Two gene expression profiles (GSE12452 and GSE13597) containing 56 nasopharyngeal carcinoma samples and 13 normal control samples were analyzed to identify the differentially expressed genes. In total, 179 up-regulated genes and 238 down-regulated genes were identified. Functional and pathway enrichment analysis showed that up-regulated genes were significantly involved in cell cycle, oocyte meiosis, DNA replication and p53 signaling pathway, while down-regulated genes were enriched in Huntington's disease,metabolic pathways. Subsequently, the top 10 hub genes, TOP2A (topoisomerase (DNA) II alpha), CDK1 (cyclin-dependent kinase 1), CCNB1 (cyclin B1), PCNA (proliferating cell nuclear antigen), MAD2L1 (mitotic arrest deficient 2 like 1), BUB1 (budding uninhibited by benzimidazoles 1 homolog), CCNB2 (cyclin B2), AURKA (aurora kinase A), CCNA2 (cyclin A2), CDC6 (cell division cycle 6 homolog), were identified from protein-protein interaction network. Furthermore, Module analysis revealed that the ten hub genes except TOP2A were belonged to module 1, indicating the upregulation of these hub genes associated molecular pathways in nasopharyngeal carcinoma might activate nasopharyngeal carcinoma pathogenesis. In conclusion, this study indicated that the identified differentially expressed genes and hub genes enrich our understanding of the molecular mechanisms of nasopharyngeal carcinoma, which could eventually translate into additional biomarkers to facilitate the early diagnosis and therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2017

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“…Regarding EC, previous studies have also confirmed the increased risk of cancer for both the Arg allele in TP53 rs1042522, as well as the combination GG and Arg-Arg variants in MDM2 and TP53 SNPs (10,11). The C allele of P14ARF rs3088440 has been found to be associated with the repression of CDKN2A, while the A allele with an impaired binding of miR-663b to the CDKN2A 3'UTR, and therefore with elevated expression of p14/p16 proteins (31)(32)(33)(34). The P14ARF rs3731217 polymorphism has been suggested to regulate the alternative splicing of CDKN2A, and the G allele to be related with higher levels of CDKN2A (35).…”

Section: Discussionmentioning

confidence: 76%

Impact ofMDM2, TP53andP14ARFPolymorphisms on Endometrial Cancer Risk and Onset

Wujcicka¹,

Zając²,

Stachowiak³

2019

In Vivo

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Background/Aim: The aim of this study was to determine the joint effect of single nucleotide polymorphisms (SNPs) of MDM2, TP53, and CDKN2A (P14ARF) genes on the onset and course of endometrial cancer (EC) in postmenopausal women. Materials and Methods: The study group consisted of 144 EC women and 50 non-cancer controls. MDM2 rs22279744, TP53 rs1042522, and P14ARF rs3088440, rs3731217, and rs3731245 SNPs were analysed.

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“…Considering the role of rs3088440, the C allele has been reported to favour the binding of c-Myb transcription factor to the transcriptional regulatory region of CDKN2A, possibly resulting in its repression and compromise of its normal function in cell cycle (16,29). In turn, the A allele has been found to be possibly associated with an impaired binding of miR-663b to the CDKN2A 3' UTR, leading to an increased expression of p14/p16 proteins (14,30). Therefore, the contribution of the T allele to EC formation seems fairly plausible through the altered binding of transcription factors to the transcriptional regulatory site of CDKN2A.…”

Section: Discussionmentioning

confidence: 99%

“…So far, distinct single nucleotide polymorphisms (SNPs) in CDKN2A (P14ARF) have been correlated with various tumours, like acute lymphoblastic leukaemia (ALL), nasopharyngeal carcinoma, medullary thyroid carcinoma, oropharyngeal cancer, oesophageal squamous cell carcinoma (ESCC), or salivary gland carcinoma (13)(14)(15)(16)(17)(18). The rs3088440 polymorphism, located in the 3' UTR region of CDKN2A, has been shown to be important in the susceptibility to and for the prognosis of several cancers, including HPV16positive oropharynx cancer, melanoma, or squamous cell carcinoma of the head and neck (SCCHN) (14,17,19). Among patients with paediatric B-cell precursor ALL (BCP-ALL), rs3731217 SNP in intron 1 of CDKN2A, has been suggested to influence the risk of cancer, by regulating alternative splicing of CDKN2A, possibly associated with the translation of p16 and p14ARF tumour suppressors ( Figure 1) (20).…”

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confidence: 99%

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

Wujcicka¹,

Zając²,

Szyłło³

et al. 2020

In Vivo

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Background/Aim: This research was aimed to evaluate the association between three selected single nucleotide polymorphisms (SNPs) within the CDKN2A (P14ARF) tumour suppressor gene and the incidence of endometrial cancer (EC) in postmenopausal women. Patients and Methods: The study included 194 postmenopausal women; 144 with EC and 50 noncancer controls. Genotypes in P14ARF rs3088440, rs3731217 and rs3731245 polymorphisms were assayed using PCR-RFLP and confirmed by sequencing. Results: Regarding the rs3088440 polymorphism, CT, and CT-TT genotypes, were more prevalent among EC patients than in controls (OR=5.55, p=0.023, OR=5.29, p=0.027; and OR=2.92, p=0.023, respectively). The T allele within rs3088440 was more prevalent in EC females than in controls (χ 2 =4.7, p=0.030). Considering rs3731217, TG and TG-GG genotypes were less prevalent among EC (OR=0.34, p=0.024 or p=0.023; and OR=0.38, p=0.035, respectively). Conclusion: Polymorphisms in the CDKN2A gene are associated with EC in postmenopausal women. Endometrial cancer (EC) is the fourth most common cancer among Polish women (after breast, colon, and lung cancer) responsible for 3% of cancer deaths in this population. Moreover, the incidence rate of this cancer has almost doubled in the last three decades, due to several factors, especially the increased average life expectancy of women. Hence, EC is predominantly observed in postmenopausal women in their sixth/seventh decade of life, with the highest incidence rate of 80/100,000 at the end of the seventh decade (1). P14ARF belongs to three tumour suppressor proteins, including p16INK4a and p15INK4b encoded by the CDKN2A gene, genetic changes of which may cause cellular proliferation and tumour growth (2, 3). It has been shown that p14ARF influenced the course of cell cycle by activating p53 and inhibiting MDM2 expression thus leading to cell cycle arrest in G 1 and G 2 /M phases (4, 5). Altered expression of p14ARF, either decreased or increased, has been found in various human tumours (5-8). Considering EC, tumor heterogeneity in CDKN2A protein expression between four different cores of primary tumours, has been reported as significantly more prevalent among samples with a higher stage of the disease (9). In another study, CDKN2A tumour suppressor gene was included in a panel of seven immunohistochemical markers [ER, CDKN2A (p16), TP53, VIM, PTEN, PGR, and IGF2BP3] to differentiate endometrioid carcinoma in FIGO grade 3 from serous carcinoma, based on immunohistochemical qualitative assays performed by tissue microarrays (10). Moreover, moderate immunohistochemical expression of p14 has been observed in endometrioid endometrial carcinoma, while total lack has been found in endometrial hyperplasias without atypia, at the 943 This article is freely accessible online.

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The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-κB pathways on the efficacy and acute toxicities of radiotherapy in patients with nasopharyngeal carcinoma

Cited by 23 publications

References 54 publications

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

Impact ofMDM2, TP53andP14ARFPolymorphisms on Endometrial Cancer Risk and Onset

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

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