Abstract 4703: Mitochondrial DNA mutations affect respiratory complex-I in never-smoker lung cancer patients and contribute to lung cancer cell growth
Bibliographic record
Abstract
Abstract Lung cancer is a deadly disease worldwide with smoking being the most important risk factor. In the United States, it is estimated that there will be over 222,550 cases of lung cancer resulting in 157,300 deaths in 2010. Despite significant improvement in therapeutic modalities, the overall 5-year survival rate is still only 15%. The high morbidity is due to the lack of early detection and therapeutic intervention. Other than nuclear genetic alterations, mitochondrial DNA mutations were reported in different human cancers and implicated to have a potential role in biomarker development. However, mtDNA alteration patterns and their potential involvement are unknown in lung cancer patients that have never smoked. In the present study, we sequenced the entire mitochondrial genome and measured the mtDNA content index by quantitative PCR in 60 lung cancer patients. Of the 60 patients, 30 never smoked and the remaining 30 patients were current smokers. Forty five percent of patients (27/60) displayed at least one somatic mtDNA mutation and a total of 41 mutations were detected which were mostly homoplasmic in nature. Strikingly, mtDNA mutations were significantly higher (P=0.0025) among the non-smokers as compared to the current smoking lung cancer patients and these mutations significantly affected (P=0.025) mitochondria encoded respiratory complex-I. The patients of Asian origin also had significantly higher (P=0.015) mtDNA mutations compared to the Caucasian patient populations. The mtDNA content index also significantly increased (P=0.037) in the non-smokers compared to the smoker lung cancer patients. Forced overexpression of a frequently observed mtDNA mutation from the ND5 gene of respiratory complex-I resulted in increased superoxide production, in vitro proliferation and invasion of lung cancer cells. Frequent mtDNA alterations are detectable in non-smoker lung cancer patients and may contribute to lung cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4703. doi:10.1158/1538-7445.AM2011-4703
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".