Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

Abstract

Purpose: The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes.Methods: Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer-specific mortality as the primary outcome.Results: In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer-specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14-2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer-specific mortality (HR=1.77; 95% CI, 1.18-2.66; P=0.006). Five-year lung cancer-specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer-specific survival (P<0.001 and 0.015, respectively), compared with low mPS.Conclusion: This study validates CCP score and mPS as independent prognostic markers for lung cancer-specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.Oncotarget 35242 www.impactjournals.com/oncotarget

MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial&ndash;mesenchymal transition in lung cancer cells

“… 5 Recently, cell cycle progression score (calculated by the average of 31 cell cycle genes normalized by the average of 15 housekeeping genes) identified by Takashi was used as an independent high-risk marker for predicting stage I lung cancer-specific mortality and quantitative risk assessment. 6 In addition, a number of molecular prognostic indicators have been reported in the literature. 7 – 9 These were examined to have association with the prognosis of stage I patients; however, only a few of them were utilized in subsequent studies.…”

AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients

“…A cell cycle progression score (CCP) including DLGAP5 and KIF11 was shown to be prognostic for different cancer entities (38,39). Concerning lung cancer, this CCP was prognostic mainly for patients with ADC (38,40). An extension of the score using TPX2 and AURKA might improve the prognostic value of the CCP score.…”

What is better/reliable, mitosis counting or Ki67/MIB1 staining?

“…Besides morphology driven approaches such as mitosis counting and the determination of PI by Ki-67 staining, it is important to note that new molecular methods such as proliferation-based gene expression signatures and derived cell cycle progression-and molecular prognostic s c o r e s m a y p r o v i d e o b j e c t i v e , q u a n t i t a t i v e , a n d reproducible stratification for prognosis and response to therapy (21). Furthermore, the emerging field of digital image analysis will substantially increase the chance for a high standardization, at least with respect to PI assessment.…”