Sequence polymorphisms of the mitochondrial displacement loop and outcome of non-small cell lung cancer

Ding, Cuimin; Li, Ruijuan; Wang, Ping; Fan, Haiyan; Guo, Zhanjun

doi:10.3892/etm.2012.490

Cited by 14 publications

(9 citation statements)

References 31 publications

(28 reference statements)

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“…However, none of the mtDNA variations were identified as independent predictors of overall survival. The association between mtDNA polymorphisms and prognosis has been analysed in various types of cancer (7,32,33). Wang et al (7) investigated the predictive power of D-loop single nucleotide polymorphisms (SNPs) in patients with HCC, and two SNP sites (nucleotides 150 C/T and 146 T/C) were identified by the log-rank test as statistically significant predictors of HCC survival.…”

Section: Discussionmentioning

confidence: 99%

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Wan

Peng

et al. 2016

Oncology Letters

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Abstract. The association between mitochondrial DNA (mtDNA) polymorphisms or mutations and the prognoses of cancer have been investigated previously, but the results have been ambiguous. In the present study, the associations between sequence variations in the mtDNA D-loop region and the outcomes of patients with hepatocellular carcinoma (HCC) were analysed. A total of 140 patients with HCC (123 males and 17 females), who were hospitalised to undergo radical resection, were studied. Polymerase chain reaction and direct sequencing were performed to detect the sequence variations in the mtDNA D-loop region. Multivariate and univariate analyses were conducted to determine important factors in the prognosis of HCC. A total of 150 point sequence variations were observed in the 140 cases (13 point mutations, 8 insertions, 20 deletions and 116 polymorphisms). The variation rate was 13.4% (150/1, 122). mtDNA nucleotide 150 (C/T) was an independent factor in the logistic regression for early/late recurrence of HCC. Patients with 150T appeared to have later recurrences. In a Cox proportional hazards regression model, hepatitis B virus DNA, Child-Pugh class, differentiation degree, tumour-node-metastasis (TNM) stage, nucleotide 16263 (T/C) and nucleotide 315 (N/insertion C) were independent factors for tumour-free survival time. Patients with the 16263T allele had a greater tumour-free survival time than patients with the 16263C allele. Similarly, patients with 315 insertion C had a superior tumour-free survival time when compared with patients with 315 N (normal). In the Cox proportional hazards regression model, recurrence type (early/late), Child-Pugh class, TNM stage and adjuvant treatment after tumour recurrence (none or one/more than one treatment) were independent factors for overall survival. None of the mtDNA variations served as independent factors. Patients with late recurrence, Child-Pugh class A, and low TNM stages and/or those who received more than one adjuvant treatment following tumour recurrence had favourable outcomes. mtDNA D-loop polymorphisms were associated with early recurrence and tumour-free survival time, but not with overall survival. mtDNA D-loop mutations in HCC were infrequent and lacked prognostic utility. The detection of mtDNA D-loop polymorphisms may assist in identifying risk factors for HCC prognosis, particularly for the short-term outcome, thereby aiding the construction of an appropriate therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Wan

Peng

et al. 2016

Oncology Letters

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“…Chronic inflammation during carcinogenesis causes ROS overproduction and implicates mtDNA damage. In NSCLC, there are frequent alterations in mtDNA D-loop which regulates mtDNA replication and expression and the D-loop SNPs (e.g., 16390A) are prognostic markers for NSCLC outcome (Ding et al 2012). The majority of the coding mtDNA mutations in lung cancers targeted complex I, and a mutation in the ND5 (G13289A) of the complex I forced its overexpression and led to lung cancer cell proliferation (Dasgupta et al 2012).…”

Section: Lung Cancermentioning

confidence: 99%

Mitochondrial biology in airway pathogenesis and the role of NRF2

Cho

Kleeberger

2019

Arch. Pharm. Res.

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A constant improvement in understanding of mitochondrial biology has provided new insights into mitochondrial dysfunction in human disease pathogenesis. Impaired mitochondrial dynamics caused by various stressors are characterized by structural abnormalities and leakage, compromised turnover, reactive oxygen species overproduction in mitochondria as well as increased mitochondrial DNA mutation frequency, which leads to impaired energy production and modified mitochondria-derived cell signaling. The mitochondrial dysfunction in airway epithelial, smooth muscle, and endothelial cells has been implicated in diseases including chronic obstructive lung diseases and acute lung injury. Increasing evidence indicates that the NRF2-antioxidant response element (ARE) pathway not only enhances redox defense but also facilitates mitochondrial homeostasis and bioenergetics. Identification of functional or potential AREs further supports the role for Nrf2 in mitochondrial dysfunction-associated airway disorders. While clinical reports indicate mixed efficacy, NRF2 agonists acting on respiratory mitochondrial dynamics are potentially beneficial. In lung cancer, growth advantage provided by sustained NRF2 activation is suggested to be through increased cellular antioxidant defense as well as mitochondria reinforcement and metabolic reprogramming to the preferred pathways to meet the increased energy demands of uncontrolled cell proliferation. Further studies are warranted to better understand NRF2 regulation of mitochondrial functions as therapeutic targets in airway disorders.

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“…We found that the highly polymorphic sequence in D‐loop that might be related to the breast cancer risk, esophageal squamous cell carcinoma, non‐Hodgkin lymphoma, kidney cancer, and lung cancer . But few studies focused on the relationships between coding region of mtDNA and HCC.…”

Section: Introductionmentioning

confidence: 99%

“…14 We found that the highly polymorphic sequence in D-loop that might be related to the breast cancer risk, esophageal squamous cell carcinoma, non-Hodgkin lymphoma, kidney cancer, and lung cancer. [15][16][17][18][19][20] But few studies focused on the relationships between coding region of mtDNA and HCC. COX genes codes three subunits of respiratory complex IV, a key enzyme as the third and final enzyme of the electron transport chain of mitochondrial oxidative phosphorylation in aerobic metabolism.…”

Section: Introductionmentioning

confidence: 99%

Identification of sequence polymorphisms in the mitochondrial cytochrome c oxidase genes as risk factors for hepatocellular carcinoma

Wang

et al. 2017

Clinical Laboratory Analysis

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Sequence polymorphisms of the mitochondrial displacement loop and outcome of non-small cell lung cancer

Cited by 14 publications

References 31 publications

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Mitochondrial biology in airway pathogenesis and the role of NRF2

Identification of sequence polymorphisms in the mitochondrial cytochrome c oxidase genes as risk factors for hepatocellular carcinoma

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