Disease recurrence after resection for stage I lung cancer

Alkattan, Khaled; Sepsas, Evangelos; Fountain, S. W.; Townsend, Edward R.

doi:10.1016/s1010-7940(97)00198-x

Cited by 130 publications

(63 citation statements)

References 9 publications

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“…For this study, we examined the marker in sputum samples from individuals who had undergone curative resection for stage I NSCLC and who were disease-free for at least 6 months before sputum sample collection ( from 6 to 36 months). These individuals are known to develop, by 3 years, tumor recurrence and/or second lung tumors at the rate of 20% to 38% postsurgery (31)(32)(33). In these individuals, 79% of specimens were judged cytologically adequate and, strikingly, ASC/TMS1 promoter methylation in sputum was present in 23.8% (10 of 42) of the patients (P V 0.05, compared with the high-risk smokers).…”

Section: Resultsmentioning

confidence: 99%

Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer

et al. 2006

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DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancerfree smokers, 15% (3 of 18) of patients with stage I non-smallcell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancerfree individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease. (Cancer Res 2006; 66(12): 6210-8)

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Section: Resultsmentioning

confidence: 99%

Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer

et al. 2006

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“…However, NSCLC is still one of the most common carcinoma characterized by a high incidence of early recurrence and poor prognosis (al-Kattan et al, 1997;Siegel et al, 2012). With the development of molecular biology, the identification of reliable biomarkers for the early diagnosis, treatment and prognostic assessment would represent an important step in the clinical management of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

Wei

Jiang²,

Chen³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Surgical resection remains the mainstay of treatment and provides the best chance for survival. However, the treatment outcome of surgery alone is unsatisfactory; the reported failure rate in stage I NSCLC ranges from 27 to 38%, and B90% of cancer deaths are associated with tumor recurrence or metastasis (al-Kattan et al, 1997;Sugimura et al, 2007;Hung et al, 2009). To improve survival, a recent meta-analysis suggests the addition of adjuvant chemotherapy after surgery for patients with operable NSCLC (Arriagada et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

et al. 2011

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We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser 473 and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and coexpression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

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Disease recurrence after resection for stage I lung cancer

Abstract: In stage I lung cancer T2 lesions requiring pneumonectomy for complete resection had a worse prognosis and higher incidence of local recurrence.

Cited by 130 publications

References 9 publications

Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer

Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer

Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

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