Brief Report: Prognostic Relevance of 3q Amplification in Squamous Cell Carcinoma of the Lung
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ABSTRACT: Introduction
Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC), with the most frequent amplified region being 3q26 to 3q28. Methods
In this analysis, we aim to describe the prognostic relevance of 3q amplification by focusing on a minimal common region (MCR) of amplification constituted of 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas and included 476 in the final analysis. Results
We identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease-specific survival (not reported [NR] versus 9.25 y, 95% confidence interval [CI]: 5.24–NR, log-rank p = 0.011) and a progression-free interval of 8 years (95% CI: 5.1–NR) versus 4.9 years (95% CI: 3.5–NR, log-rank p = 0.020). Multivariable analysis revealed that MCR amplification was associated with improved disease-specific survival and progression-free interval. Conclusions
Amplification of the 25-gene MCR within 3q was present in 44% of this cohort, consisting mainly of Caucasian patients with early stage LUSC. This analysis strongly indicates the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic and predictive relevance in a racially diverse patient population with advanced LUSC.
SUBMITTER: Abu Rous F
PROVIDER: S-EPMC10070899 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Project description:BackgroundLung squamous cell carcinoma (LUSC), as the second frequent subtype of lung cancer, causes lots of mortalities primarily due to a lack of precise prognostic markers and timely treatment intervention. Previous studies have constructed several risk prognostic models based on DNA methylation sites in multiple tumors, whereas, DNA methylation signature of LUSC remains to be built, and its predictive value need to be evaluated.MethodsThe genome-wide DNA methylation data of LUSC samples was obtained from The Cancer Genome Atlas dataset. Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) were implemented to identify DNA methylation sites related to overall survival of LUSC patients. Thus, we performed multivariate Cox regression to establish a DNA methylation signature. The Kaplan-Meier (K-M) survival curves and time-dependent receiver operating characteristic (ROC) curves were plotted to estimate the prognostic power of the signature. Comparison with other known prognostic biomarkers, our DNA methylation signature showed higher predictive specificity and sensitivity. In addition, multivariate Cox regression screened out independent prognostic factors and constructed a nomogram.ResultsSeveral statistical methods were performed to construct an 11-DNA methylation signature. LUSC patients were divided into low- and high-risk group based on risk score, and high-risk group had a shorter survival time. According to the results of K-M and ROC analyses, the 11-DNA methylation signature showed significant sensitivity and specificity in predicting the LUSC patients' overall survival. Finally, we integrated some independent prognostic factors (risk score, metastasis stage, and tobacco smoking history) to construct a nomogram, which has excellent prognostic power and may provide guidance for the therapeutic strategies.ConclusionsWe constructed the first risk prognosis model based on DNA methylation site in LUSC, which showed better predictive ability. In addition, a nomogram integrating the DNA methylation signature, metastasis stage, and tobacco smoking history was developed.
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