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Development of a prognosis-prediction model incorporating genetic polymorphism with pathologic stage in stage I non-small cell lung cancer: A multicenter study.

ABSTRACT: This multicenter study was performed to develop a prognosis-prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non-small cell lung cancer (NSCLC) patients.A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression.Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis-prediction model, we categorized patients into low, intermediate, and high-risk groups, which had greater accuracy in predictive ability (log-rank statistics?=?54.66) than the conventional tumor node metastasis staging (log-rank statistics?=?39.56). Next, we generated a prognosis-prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high-risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy.This prognosis-prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.

SUBMITTER: Lee WK

PROVIDER: S-EPMC5415483 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Development of a prognosis-prediction model incorporating genetic polymorphism with pathologic stage in stage I non-small cell lung cancer: A multicenter study.

Lee Won Kee WK Lee Shin Yup SY Choi Jin Eun JE Seok Yangki Y Lee Eung Bae EB Lee Hyun Cheol HC Kang Hyo-Gyoung HG Yoo Seung Soo SS Lee Myung Hoon MH Cho Sukki S Jheon Sanghoon S Kim Young Chul YC Oh In Jae IJ Na Kook Joo KJ Jung Chi Young CY Park Chang-Kwon CK Kim Mi-Hyun MH Lee Min Ki MK Park Jae Yong JY

Thoracic cancer 20170331 3

<h4>Background</h4>This multicenter study was performed to develop a prognosis-prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non-small cell lung cancer (NSCLC) patients.<h4>Methods</h4>A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies includ ...[more]

PMID: 28371058

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Project description:BackgroundAlthough more pathologic stage-I lung adenocarcinoma (LUAD) was diagnosed recently, some relapsed or distantly metastasized shortly after radical resection. The study aimed to identify biomarkers predicting prognosis in the pathologic stage-I LUAD and improve the understanding of the mechanisms involved in tumorigenesis.MethodsWe obtained the expression profiling data for non-small cell lung cancer (NSCLC) patients from the NCBI-GEO database. Differentially expressed genes (DEGs) between early-stage NSCLC and normal lung tissue were determined. After function enrichment analyses on DEGs, the protein-protein interaction (PPI) network was built and analyzed with the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Overall survival (OS) and mRNA levels of genes were performed with Kaplan-Meier analysis and Gene Expression Profiling Interactive Analysis (GEPIA). qPCR and western blot analysis of hub genes in stage-I LUAD patients validated the significant genes with poor prognosis.ResultsA total of 172 DEGs were identified, which were mainly enriched in terms related to management of extracellular matrix (ECM), receptor signaling pathway, cell adhesion, activity of endopeptidase, and receptor. The PPI network identified 11 upregulated hub genes that were significantly associated with OS in NSCLC and highly expressed in NSCLC tissues compared with normal tissues by GEPIA. Elevated expression of ANLN, EXO1, KIAA0101, RRM2, TOP2A, and UBE2T were identified as potential risk factors in pathologic stage-I LUAD. Except for ANLN and KIAA0101, the hub genes mRNA levels were higher in tumors compared with adjacent non-cancerous samples in the qPCR analysis. The hub genes protein levels were also overexpressed in tumors. In vitro experiments showed that knockdown of UBE2T in LUAD cell lines could inhibit cell proliferation and cycle progression.ConclusionsThe DEGs can probably be used as potential predictors for stage-I LUAD worse prognosis and UBE2T may be a potential tumor promoter and target for treatment.

Project description:ObjectiveThe study objective was to evaluate the influence of surgeon experience on outcomes in early-stage non-small cell lung cancer.MethodsIn an institutional database, patients undergoing operations for pathologic stage I non-small cell lung cancer were categorized by surgeon experience: within 5 years of completion of training, the low experience group; with 5 to 15 years of experience, the moderate experience group; and with more than 15 years, the high experience group.ResultsFrom 2000 to 2012, 800 operations (638 lobectomies, 162 sublobar resection) were performed with the following distribution: low experience 178 (22.2%), moderate experience 224 (28.0%), and high experience 398 (49.8%). Patients in the groups were similar in age and comorbidities. The use of video-assisted thoracoscopic surgery was higher in the moderate experience group (low experience: 62/178 [34.8%], moderate experience: 151/224 [67.4%], and high experience: 133/398 [33.4%], P < .001), as was the mean number of mediastinal (N2) lymph node stations sampled (low experience: 2.8 ± 1.6, moderate experience: 3.5 ± 1.7, high experience: 2.3 ± 1.4, P < .001). The risk of perioperative morbidity was similar across all groups (low experience: 54/178 [30.3%], moderate experience: 51/224 [22.8%], and high experience: 115/398 [28.9%], P = .163). Five-year overall survival in the moderate experience group was 76.9% compared with 67.5% in the low experience group (P < .001) and 71.4% in the high experience group (P = .006). In a Cox proportional hazard model, increasing age, male gender, prior cancer, and R1 resection were associated with an elevated risk of mortality, whereas being operated on by surgeons with moderate experience and having a greater number of mediastinal (N2) lymph node stations sampled were protective.ConclusionsThe experience of the surgeon does not affect perioperative outcomes after resection for pathologic stage I non-small cell lung cancer. At least moderate experience after fellowship is associated with improved long-term survival.

Dataset Information

Development of a prognosis-prediction model incorporating genetic polymorphism with pathologic stage in stage I non-small cell lung cancer: A multicenter study.

Publications

Development of a prognosis-prediction model incorporating genetic polymorphism with pathologic stage in stage I non-small cell lung cancer: A multicenter study.

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