Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival.
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ABSTRACT:
SUBMITTER: Belien JA
PROVIDER: S-EPMC2743350 | biostudies-other | 2009 Sep
REPOSITORIES: biostudies-other
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Project description:ImportanceThe mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood.ObjectiveTo test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival.DesignRetrospective cohort study.SettingAcademic Medical Center (Massachusetts General Hospital, Boston).Participants240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging.Measurements18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV).ResultsAmong individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001).Conclusions and relevanceAmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.
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Project description:Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years' survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (-1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = -0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.
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Project description:Heparan sulfate proteoglycan 2 (HSPG2), also known as perlecan, is a large multi-domain extracellular matrix proteoglycan, which contributes to the invasion, metastasis and angiogenesis of solid tumor. However, very little is known about the effect of HSPG2 on acute myeloid leukemia (AML). This study aims to investigate the prognostic value of the HSPG2 gene in terms of overall survival and leukemia-free survival in patients with AML. Bone marrow mononuclear cells (BMMCs) from 4 AML patients and 3 healthy controls were processed for RNA-Sequencing (RNA-seq). The mRNA expression level of HSPG2 in BMMCs and CD34+ hematopoietic stem/progenitor cells (HSPC) obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR. Then the correlations between the expression of HSPG2 and a variety of important clinical parameters, such as median white blood cell (WBC) count and bone marrow (BM) blasts, were further analyzed. The expression level of HSPG2 was significantly upregulated in AML patients at the time of diagnosis, downregulated after complete remission and then elevated again at relapse. Moreover, HSPG2 expression was associated with median WBC count (P < 0.001), median hemoglobin (P = 0.02), median platelet count (P = 0.001), and BM blasts (P < 0.001) in AML patients. Patients with high HSPG2 expression had both worse overall survival (OS) (P = 0.001) and poorer leukemia-free survival (LFS) (P = 0.047). In the multivariate analysis model, HSPG2 was identified as an independent prognostic biomarker of AML. Taken together, these results indicate that HSPG2 overexpression was associated with poor prognosis in AML patients, and may be a prognostic biomarker and therapeutic target of AML.
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Project description:BackgroundSF3B1 mutations (SF3B1mut ) in myelodysplastic syndromes (MDS) frequently involve codon K700E and have a favorable prognosis. The prognostic effect of non-K700E SF3B1mut is uncertain.MethodsThe authors analyzed the clinicopathological features and outcomes of a single-institution series of 94 treatment-naive SF3B1mut MDS patients (18%) and 415 treatment-naive SF3B1wt MDS patients and explored the differences between K700E and non-K700E SF3B1mut MDS.ResultsFifty-five patients (59%) carried K700E. Recurrent non-K700E mutations (39 [41%]) included R625, H662, and K666. Compared with SF3B1mut K700E patients, non-K700E patients had a lower median absolute neutrophil count (1.8 vs 2.4; P = .005) and were frequently "high" according to the Revised International Prognostic Scoring System (19% vs 4%; P = .031). Non-K700E MDS was associated frequently with RUNX1 (26% vs 7%; P = .012) and exclusively with BCOR, IDH2, and SRSF2 mutations. A splicing analysis showed the differential distribution of alternatively spliced events and gene expression profiles between K700 and non-K700E MDS patients. The majority (at least 80%) of SF3B1mut K700E, SF3B1mut non-K700E, and SF3B1wt patients were treated with hypomethylating agents. Over a median follow-up of 16 months, SF3B1mut had superior overall survival (OS) in comparison with SF3B1wt in all MDS patients (not reached vs 25.2 months; P = .0003), in patients with low-grade MDS, and in patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS). Compared with SF3B1wt , SF3B1mut K700E had superior outcomes in all MDS (median OS, 25 months vs not reached; P = .0001), in low-grade MDS (median OS, 41.3 months vs not reached; P = .0015), and in MDS-RS (median OS, 22.3 months vs not reached; P = .0001), but no significant difference was seen between non-K700E and SF3B1wt MDS. By multivariable analysis, the absence of SF3B1mut K700E mutations was independently associated with the prognosis.ConclusionsThis study highlights the importance of the SF3B1 mutation subtype in MDS risk assessment.Lay summaryMyelodysplastic syndromes (MDS) with SF3B1 mutations are regarded as having a favorable prognosis by both the World Health Organization and the International Working Group for the Prognosis of Myelodysplastic Syndromes. However, this article shows that only MDS patients with SF3B1 K700E mutations have a favorable prognosis (and not MDS patients with SF3B1 mutations involving other codons). This has important implications for refining future MDS subclassification and risk assessment criteria.
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Project description:BackgroundNeoadjuvant chemoradiotherapy (neo-CRT) plus surgery has greatly improved the prognosis of locally advanced esophageal cancer (EC) patients. But which factors may influence the pathological tumor response and long-term survival remains unclear. The purpose of this study was to identify the prognostic biomarkers of locally advanced EC patients receiving neo-CRT.MethodsWe reviewed the data of 72 patients with cT2-4N0-3M0 EC who underwent neo-CRT at our hospital. The patients received intensity-modulated radiation therapy with a total radiation dose of 41.4-60.0 Gy. Most patients received platinum + paclitaxel-based combination regimens every three weeks for 2-4 cycles. The recorded data included age, sex, smoking history, alcohol use, histology, tumor location, clinical TNM stage, tumor length, gross tumor volume (GTV), GTV of primary tumor (GTVp), GTV of lymph nodes (GTVn), radiation dose, and number of chemotherapy cycles. Overall survival (OS), progression-free survival (PFS), and pathological complete response (pCR) were analyzed.ResultsThe 3-year OS and PFS rates of these patients who underwent neo-CRT were 51.14% and 43.28%, respectively. In the univariate analyses, smoking history, clinical stage, GTV, GTVp, and GTVn were significantly associated with OS, whereas alcohol use, GTV, GTVp, and GTVn were significantly associated with PFS. Furthermore, in the multivariate analysis, GTV was an independent prognostic predictor of OS (hazard ratio (HR): 14.14, 95% confidence interval (CI): 3.747-53.33, P < 0.0001) and PFS (HR: 6.090, 95% CI: 2.398-15.47, P < 0.0001). In addition, GTV < 60.50 cm3 compared to > 60.50 cm3 was significantly associated with higher pCR rate (59.3% and 27.8%, respectively, P = 0.038). High dose (> 50 Gy) and increased number of chemotherapy cycles (≥ 3) didn't improve the OS or PFS in patients with GTV > 60.50 cm3.ConclusionGTV was an independent prognostic factor of long-term survival in EC patients, which may be because GTV is associated with histological response to neo-CRT. Additionally, patients with GTV > 60.50 cm3 didn't benefit from increased radiation dose or increased number of chemotherapy cycles.
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