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The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.

ABSTRACT: Stage IA non-small-cell lung cancer cases have been recognized as having a low risk of relapse; however, occasionally, relapse may occur. To predict clinical outcome in Stage IA non-small-cell lung cancer patients, we searched for chimeric transcripts that can be used as biomarkers and identified a novel chimeric transcript, RUNX1-GLRX5, comprising RUNX1, a transcription factor, and GLRX5. This chimera was detected in approximately half of the investigated Stage IA non-small-cell lung cancer patients (44/104 cases, 42.3%). Although there was no significant difference in the overall survival rate between RUNX1-GLRX5-positive and -negative cases (P = 0.088), a significantly lower relapse rate was observed in the RUNX1-GLRX5-positive cases (P = 0.039), indicating that this chimera can be used as a biomarker for good prognosis in Stage IA patients. Detection of the RUNX1-GLRX5 chimeric transcript may therefore be useful for the determination of a postoperative treatment plan for Stage IA non-small-cell lung cancer patients.

SUBMITTER: Ishikawa R

PROVIDER: S-EPMC4731000 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.

Ishikawa Rie R Amano Yosuke Y Kawakami Masanori M Sunohara Mitsuhiro M Watanabe Kousuke K Kage Hidenori H Ohishi Nobuya N Yatomi Yutaka Y Nakajima Jun J Fukayama Masashi M Nagase Takahide T Takai Daiya D

Japanese journal of clinical oncology 20151218 2

Stage IA non-small-cell lung cancer cases have been recognized as having a low risk of relapse; however, occasionally, relapse may occur. To predict clinical outcome in Stage IA non-small-cell lung cancer patients, we searched for chimeric transcripts that can be used as biomarkers and identified a novel chimeric transcript, RUNX1-GLRX5, comprising RUNX1, a transcription factor, and GLRX5. This chimera was detected in approximately half of the investigated Stage IA non-small-cell lung cancer pat ...[more]

PMID: 26685324

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Project description:BackgroundLung cancer serum tumor markers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrate antigen 125(CA125) as prognostic predictors is controversial. Therefore, this study aimed to evaluate the association between these markers and the survival of patients with postoperative stage III-N2 non-small cell lung cancer (NSCLC).MethodsWe enrolled 1011 patients with pathologically confirmed stage III-N2 NSCLC who underwent resection and whose pretreatment serum tumor marker levels were available. Patients were categorized according to their serum levels into low-, medium-, and high-risk groups. Overall survival (OS), progression-free survival (PFS), local regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated from the date of resection. Their association with each serum tumor marker was assessed using the log-rank test.ResultsAbnormal CEA levels were associated with worse five-year OS, PFS and DMFS; abnormal CYFRA21-1 levels were associated with worse five-year OS and LRFS; and abnormal CA125 levels were associated with worse five-year OS, PFS, LRFS and DMFS. Among the risk groups, there were significant differences in five-year OS, PFS, LRFS and DMFS (P = 0.000). In propensity score matching analysis, the model also achieved prognostic significance for all four survival classifications (P = 0.001-0.004) among the three risk groups.ConclusionsThe combined model achieved prognostic significance for all survival outcome types. The serum tumor markers tested are useful prognostic predictors for postoperative NSCLC patients but not for all survival outcomes. The combination of the three indices is more reliable in predicting all four of the survival outcomes.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: Serum CEA, CYFRA21-1, and CA125 levels can be used as prognostic factors of postoperative N2 non-small cell lung cancer patients but not for all survival outcomes, suggesting that combinative detection of all three indices would be more reliable.What this study addsOur model utilizes available technology, with conventional cutoff values, inexpensive costs, and simple mathematics methods and, thus, can be feasibly employed by clinicians or oncologists.

Project description:BackgroundNon-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival of only 21%. Reliable prognostic and/or predictive biomarkers are needed to improve NSCLC patient stratification, particularly in curative disease stages. Since the endogenous cannabinoid system is involved in both carcinogenesis and anticancer immune defense, we hypothesized that tumor tissue expression of cannabinoid 1 and 2 receptors (CB1 and CB2) may affect survival.MethodsTumor tissue samples collected from 100 NSCLC patients undergoing radical surgery were analyzed for CB1 and CB2 gene and protein expression using the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The gene and protein expression data were correlated with disease stage, histology, tumor grading, application of chemotherapy, and survival. Additional paired tumor and normal tissue samples of 10 NSCLC patients were analyzed independently for comparative analysis of CB1 and CB2 gene expression.ResultsPatients with tumors expressing the CB2 gene had significantly longer overall survival (OS) (P<0.001), cancer specific survival (CSS) (P=0.002), and disease-free survival (DFS) (P<0.001). They also presented with fewer lymph node metastases at the time of surgery (P=0.011). A multivariate analysis identified CB2 tumor tissue gene expression as a positive prognostic factor for CSS [hazard ratio (HR) =0.274; P=0.013] and DFS (HR =0.322; P=0.009), and increased CSS. High CB2 gene and protein expression were detected in 79.6% and 31.5% of the tested tumor tissue samples, respectively. Neither CB1 gene nor CB1 or CB2 protein expression affected survival. When comparing paired tumor and tumor-free lung tissue samples, we observed reduced CB1 (P=0.008) and CB1 (P=0.056) gene expression in tumor tissues.ConclusionsIn NSCLC patients undergoing radical surgery, expression of the CB1 and CB2 receptor genes is significantly decreased in neoplastic versus tumor-free lung tissue. CB2 tumor tissue gene expression is strongly associated with longer survival (OS, CSS, DFS) and fewer lymph node metastases at the time of surgery. More studies are needed to evaluate its role as a biomarker in NSCLC and to investigate the potential use of CB2 modulators to treat or prevent lung cancers.

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Project description:BackgroundThe increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy.MethodsWe conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions.ResultsFrom June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group.ConclusionsIn patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

Dataset Information

The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.

Publications

The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.

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