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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis

GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was previously characterized as a tumor suppressor that regulates and requires merlin to suppress cell proliferation. However, the role of GTPBP4 in the metastasis of colorectal carcinoma (CRC) remains unelucidated. Here, we observed that GTPBP4 was detected at higher levels in CRC metastatic tissues than that in the primary tumor tissues. Notably, up-regulation of GTPBP4 was closely correlated with tumor metastasis in CRCs. Kaplan-Meier and multivariate Cox regression analysis indicated GTPBP4 as an independent prognostic factor for CRC patients (hazard ratio = 2.693, 95% confident interval: 1.193–6.083, p = 0.017). Functional studies established that knockdown of GTPBP4 impeded, whereas ectopic expression of GTPBP4 enhanced cell motility and tumor metastasis in CRC cells. Interestingly, mechanistic investigations suggested that GTPBP4 may disorganize actin cytoskeleton through repressing RhoA signaling. Taken together, our research uncovered that GTPBP4 promotes CRC metastasis by disrupting actin cytoskeleton, which is mediated by the reduced RhoA activity. Strategies targeting GTPBP4 will be promising for CRC patients with metastases. - Highlights: • Up-regulation of GTPBP4 is detected in CRC metastatic tissues and closely correlated with tumor metastasis. • Increase of GTPBP4 is closely associated with poor prognosis. • GTPBP4 promotes cell motility and tumor metastasis in CRC cells. • GTPBP4 induces filamentous actin rearrangement specifically by repressing the activity of RhoA. • GTPBP4 may be a novel therapeutic target for CRC patients with metastasis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

NCOA5 is correlated with progression and prognosis in luminal breast cancer

Nuclear receptor coactivator 5 (NCOA5) is known to modulate ERα-mediated transcription and has been found to be involved in the progression of several malignancies. However, the potential correlation between NCOA5 and clinical outcome in patients with luminal breast cancer remains unknown. In the present study, we demonstrated that NCOA5 was significantly up-regulated in luminal breast cancer tissues compared with adjacent non-cancerous tissues both in validated cohort and TCGA cohort. Moreover, Kaplan-Meier analysis indicated that patients with high NOCA5 expression had significantly lower overall survival (P = 0.021). Cox regression analysis indicated that the high NOCA5 expression was independent high risk factor as well as old age (>60) and HER-2 expression (P = 0.039; P = 0.003; P = 0.005; respectively). This study provides new insights and evidences that NOCA5 over-expression was significantly correlated with progression and prognosis in luminal breast cancer. However, the precise cellular mechanisms for NOCA5 in luminal breast cancer need to be further explored. - Highlights: • NCOA5 is significantly over-expressed in human luminal breast cancer tissues. • NOCA5 was involved in the progression of luminal breast cancer. • NCOA5 can predict the progression of luminal breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Prognostic significance of high YY1AP1 and PCNA expression in colon adenocarcinoma

Highlights: • YY1AP1 expression might play an important role in the tumorgenesis of colon adenocarcinoma. • YY1AP1 expression is related with colon adenocarcinoma patient M-class/distant metastasis. • High YY1AP1 indicates poor overall survival of colon adenocarcinoma patients. • Cox proportional-hazards model analysis indicated YY1AP1 as an independent predictor for overall survival. To investigate the relationship between YY1AP1 and various clinicopathological features of colon adenocarcinoma (COAD), we conducted immunohistochemical (IHC) analyses of human tissue microarrays. We found that YY1AP1 protein expression was significantly higher in tumor tissue of the colon and liver, and was significantly lower in tumor tissue of the kidney. An analysis that employed the SurvExpress database indicated that increased expression of YY1AP1 mRNA was significantly associated with the overall survival of COAD patients. To clarify the validity of YY1AP1 or PCNA as determined by the IHC analysis was performed on 59 paired samples from COAD and adjacent normal tissue. Statistically significant differences of immunoreactivity for YY1AP1 or PCNA protein expression was observed between COAD tissue and adjacent normal tissue. High protein expression levels of YY1AP1 and PCNA were also found to be significantly correlated with M-class and distant metastasis. We also determined that YY1AP1 was correlated with PCNA expression in COAD samples, and Kaplan-Meier survival curves indicated that YY1AP1 protein expression was significantly associated with poor survival. Finally, a univariate analysis demonstrated that YY1AP1 protein expression was related to YY1AP1 score, and multivariate analysis revealed that the YY1AP1 protein expression level was an independent risk factor of overall COAD survival. Taken together, our findings indicate that YY1AP1 expression plays an important role in the tumorigenesis and progression of COAD and could serve as a clinical prognostic indicator for COAD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

FOXK1 plays an oncogenic role in the development of esophageal cancer

Forkhead box k1 (FOXK1) is a member of the FOX class of transcription factors and it is dysregulated in many solid tumors including hepatocellular carcinoma, gastric cancer, colorectal cancer and prostate cancer. However, the expression status of FOXK1 and its clinical significance in esophageal cancer (EC) is still uncertain. Our study aimed at investigating the significance of FOXK1 expression in human EC and its biological function in the development of EC. We found that FOXK1 was overexpressed in EC tissues compared with corresponding non-tumor tissues using immunohistochemistry. And high FOXK1 expression was related to poor differentiation of EC. The Kaplan-Meier curve indicated that high FOXK1 expression may result in poor prognosis of EC patients. Furthermore, overexpression of FOXK1 in EC9706 cell inhibited cell apoptosis and promoted cell proliferation and migration, and suppression of FOXK1 in EC109 cell obtained reverse results. Our data suggest that FOXK1 plays an oncogenic role in EC pathogenesis and can serve as a therapeutic target for patients with EC. - Highlights: • It's the first time investigating the relationship between FOXK1 and esophageal cancer (EC). • FOXK1 could inhibit cell apoptosis and promote cell proliferation and migration of EC in vitro. • FOXK1 plays an oncogenic role in EC pathogenesis and can serve as a therapeutic target for patients with EC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Downregulation of Nedd4L predicts poor prognosis, promotes tumor growth and inhibits MAPK/ERK signal pathway in hepatocellular carcinoma

Highlights: • Nedd4L is down-regulated in HCC tissues. • Downregulation of Nedd4L predicts poor prognosis of HCC. • Nedd4L inhibits the proliferation of HCC in vitro and in vivo. • Nedd4L phosphorylates ERK1/2 and regulates genes related with apoptosis. Accumulating evidence indicates that the neural precursor cell–expressed, developmentally downregulated 4–like (Nedd4L) related with some tumor progression pathways and was found abnormally expressed in several kinds of solid cancers. However, the role and mechanism of Nedd4L in HCC remain unknown. This study was to assess the role of Nedd4L in HCC tumorigenesis and prognosis. The real-time quantitative RT-PCR and immunohistochemistry results revealed that Nedd4L was downregulated in HCC tissues compared to corresponding peri-noncancerous tissue, and HCC patients with low expression of Nedd4L exhibited poor prognosis assessed by Kaplan-Meier and Cox regression analysis in 78 HCC patients. Furthermore, knockdown of Nedd4L could significantly promote proliferation of HCC cells by CCK-8 and colony formation assays in vitro; whereas ectopic expression of Nedd4L resulted in attenuating proliferation in vitro and tumor growth in vivc determined by nude mice xenografts model. Mechanically, Nedd4L could phosphorylate ERK1/2 and regulate genes related with apoptosis. Collectively, Nedd4L plays a tumor suppressive role in HCC, possibly through triggering MAPK/ERK-mediated apoptosis, and Nedd4L downregulation may be a potential prognostic biomarker as well as a therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA TP73-AS1 predicts the prognosis of bladder cancer patients and functions as a suppressor for bladder cancer by EMT pathway

Highlights: • LncRNA TP73-AS1 is identified with downregulation in bladder cancer tissues and cell lines. • Patients with low TP73-AS1 have shorter overall survival and progression-free survival. • Overexpression of TP73-AS1 can inhibit cell growth, migration, and invasion in vitro study. • Overexpression of TP73-AS1 inhibits metastasis of bladder cancer cell through inactivating EMT pathway. • We firstly reported the tumor suppressor function of TP73-AS1 in bladder cancer. Long noncoding RNAs (lncRNAs) have been identified to have more and more important roles in tumorigenesis and may be novel biomarker for cancer therapy. LncRNA TP73-AS1 is a novel identified lncRNA that has been demonstrated to be increased in several cancers, however, its function in bladder cancer remains unknown. The aim of this work was to examine the expression and role of lncRNA TP73-AS1 in bladder cancer. The expression levels of lncRNA TP73-AS1 in bladder cancer tissues and cell lines were determined by quantitative real-time PCR (qRT-PCR), and its clinical significance was assessed by statistical analysis. Moreover, by gain-of-function assay, the effect of TP73-AS1 on proliferation, cell cycle, apoptosis, migration and invasion was examined in bladder cancer cells. We identified that the expression level of TP73-AS1 was significantly down-regulated in bladder cancer tissues and cells compared to adjacent non-tumor tissues. Kaplan-Meier survival analysis found that patients with low TP73-AS1 expression level had shorter overall survival and progression-free survival than those with high TP73-AS1 expression. Moreover, we showed that overexpression of TP73-AS1 could inhibit cell growth, arrest cell cycle, reduce cell migration and invasion, and promote cell apotosis in vitro study. In addition, overexpression of TP73-AS1 diminished epithelial-mesenchymal transition (EMT) through inhibiting the expression of vimentin, snail, MMP-2, and MMP-9 and upregulating the expression levels of E-cadherin. Collectively, our findings for the first time elucidated that lncRNA TP73-AS1 may serve as a tumor suppressor participated in bladder cancer progression, which provided a promising therapy strategy for patients with bladder cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Spindle pole body component 25 homolog expressed by ECM stiffening is required for lung cancer cell proliferation

Highlights: • Matrix stiffness regulates the expression of genes involved in cell proliferation. • SPC25 is identified as hazard gene induced by matrix stiffness. • SPC25 is involved in cancer cell proliferation under stiff matrix conditions. • Depletion of SPC25 induces G2/M arrest via chromosome misalignment in metaphase. Accumulating evidence has shown that matrix stiffening in cancer tissue by the deposition of extracellular matrix (ECM) is closely related with severe tumor progression. However, much less is known about the genes affected by matrix stiffness and its signaling for cancer progression. In the current research, we investigated the differential gene expression of a non-small lung adenocarcinoma cell line, H1299, cultured under the conditions of soft (∼0.5 kPa) and stiff (∼40 kPa) matrices, mimicking the mechanical environments of normal and cancerous tissues, respectively. For integrated transcriptome analysis, the genes identified by ECM stiffening were compared with 8248 genes retrieved from The Cancer Genome Atlas Lung Adenocarcinoma (TCGA). In stiff matrix, 29 genes were significantly upregulated, while 75 genes were downregulated. The screening of hazard ratios for these genes using the Kaplan-Meier Plotter identified 8 genes most closely associated with cancer progression under the condition of matrix stiffening. Among these genes, spindle pole body component 25 homolog (SPC25) was one of the most up-regulated genes in stiff matrix and tumor tissue. Knockdown of SPC25 in H1299 cells using shRNA significantly inhibited cell proliferation with downregulation of the expression of checkpoint protein, Cyclin B1, under the condition of stiff matrix whereas the proliferation rate in soft matrix was not affected by SPC25 silencing. Thus, our findings provide novel key molecules for studying the relationship of extracellular matrix stiffening and cancer progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Over-expression of lysyl oxidase is associated with poor prognosis and response to therapy of patients with lower grade gliomas

Lower grade gliomas (LGGs) have highly diverse clinical phenotypes. The histological grade and type are insufficient to accurately predict the clinical outcomes of patients with LGGs. Therefore, identification of biomarkers that can facilitate the prediction of clinical outcomes in LGGs is urgently needed. Gene expression of LOX has been identified as a biomarker for various cancers. However, the clinical significance of LOX expression in LGGs has not been investigated. In this study, we analyzed the glioma RNA-seq dataset from TCGA (The Cancer Genome atlas) and identified lysyl oxidase (LOX) as a potential biomarker for LGGs. Kaplan-Meier survival analysis revealed that high LOX expression is associated with worse overall survival and recurrence free survival in LGG patients. Besides, high LOX expression is associated with poor response to primary therapy, follow-up treatment, targeted molecular therapy, and radiation therapy. Univariate and multivariate Cox regression analyses further confirmed LOX expression as an independent prognostic factor for LGG patients. Finally, we observed that LOX expression is significantly correlated with EMT (epithelial to mesenchymal transition) and IDH1 status in LGGs. In conclusion, our analyses suggest that LOX expression is a potential biomarker for prognosis and therapeutic response in LGGs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Neutrophils infiltrating pancreatic ductal adenocarcinoma indicate higher malignancy and worse prognosis

Highlights: • Previous studies have reported that inflammation and peroxides may promote development of pancreatic ductal adenocarcinoma (PDAC). • Neutrophils, as inflammatory cells, can produce or peroxides in the stroma of cancer. . • It is difficult to investigate the interaction between neutrophils and PDAC cells. Here, CD177 was used to show distribution of neutrophils. • Expression of CD177 was negatively correlated with overall survival of patients. This phenomenon was observed from pathological specimens. • Therefore, we speculate that neutrophils infiltration is a negative prognostic factor for PDAC. CD177 is considered to represent neutrophils. We analyzed mRNA expression level of CD177 and clinical follow-up survey of PDAC to estimate overall survival (OS) from Gene Expression Omnibus (GEO) dataset (GSE21501, containing samples from 102 PDAC patients) by R2 platform (http://r2.amc.nl). We also analyzed correlated genes of CD177 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict the potential relationship between neutrophils and prognosis of PDAC. We then performed hematoxylin and eosin (H&E) staining and immunohistochemical staining of surgical specimens to verify infiltration of neutrophils in PDAC tissues. After analyzing mRNA expression data and clinical follow-up survey provided in the GEO dataset (GSE21501, containing samples from 102 PDAC patients) and clinicopathological data of 23 PDAC patients, we demonstrated that CD177 was correlated with poor prognosis. The univariate Kaplan–Meier survival analysis revealed that OS was inversely associated with increased expression of CD177 (P = 0.012). Expression of phosphodiesterase (PDE)4D was positively related to CD177 in gene correlation analysis (R = 0.413, P < 0.001) by R2 platform. H&E staining and immunohistochemistry of CD177 in 23 PDAC surgical samples showed accumulation of neutrophils in the stroma and blood vessels around the cancer cells. In addition, immunohistochemical staining showed that CD177 was highly expressed in the stroma and blood vessels around tumor tissues of PDAC, which was similar to H&E staining. Expression of CD177 can be used to represent infiltration of neutrophils, which may have potential prognostic value in PDAC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A

Highlights: • Exosomal miR-93 is up-regulated both in HCC cell lines' media and HCC patients' serum. • Exosomal miR-93 promotes HCC proliferation and invasion by regulating TIMP2/TP53INP1/CDKN1A. • Exosomal miR-93 is correlated with clinical information including stage, tumor size and predict patients' survival rate. Hepatocellular carcinoma (HCC) is a malignant cancer worldwide; lacking biomarkers for early prognostication contributes to its high lethality. Herein, we report a novel biomarker, exosome delivered miR-93, is up-regulated in HCC cell line media and serum samples of HCC patients. We measured the proliferation and invasion ability of HCC cell lines following exosomal miR-93 treatment. After prediction with online algorithms, we further confirmed that TP53INP1, TIMP2 and CDKN1A are direct targets of miR-93 by dual-luciferase reporter assay. In addition, the diagnostic value of exosomal miR-93 was evaluated by qPCR and ROC analysis. The significant correlation between serum exosomal miR-93 and clinical information including stage, tumor size were observed. Furthermore, the survival differences of HCC patients with high or low miR-93 were statistically significant using Kaplan-Meier analysis. In summary, our work identified exosomal miR-93 as a novel biomarker for both diagnosis and prognosis in HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-410–3p promotes prostate cancer progression via regulating PTEN/AKT/mTOR signaling pathway

Prostate cancer has become one of commonest urologic tumors in male. In recent years, miRNAs are continually attracting attentions of researchers for their special regulatory function in human cancers. Previous study has revealed that miR-410 acts as a biomarker for the diagnosis of prostate cancer. Whereas, the specific biological function of miR-410–3p in prostate cancer remains unknown. The aim of this study is to explore the function and molecular mechanism of miR-410–3p in prostate cancer. The high expression of miR-410–3p was examined in prostate cancer tissues and cell lines by qRT-PCR. Next, the prognostic value was identified by Kaplan Meier method. High expression of miR-410–3p indicated poor prognosis of prostate cancer patients. To investigate the biological function of miR-410–3p in prostate cancer, loss-of function assays were designed and performed in two prostate cancer cell lines (PC3 and DU145). As a result, downregulated miR-410–3p suppressed cell proliferation, migration and EMT progress. Moreover, flow cytometry analysis was performed to determine that the acceleration effects of miR-410–3p on cell apoptosis. Mechanistically, further analysis demonstrated that the effects of miR-410–3p exert oncogenic functions through downregulating PTEN. All findings in this study revealed that miR-410–3p inhibits prostate cancer progression via downregulating PTEN/AKT/mTOR signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA circ{sub 0}001649 acts as a prognostic biomarker and inhibits NSCLC progression via sponging miR-331-3p and miR-338-5p

Accumulating evidence documented the key functions of circular RNAs (circRNAs) in various malignancies. However, the study regarding the involvement of circRNAs in non-small cell lung cancer (NSCLC) has just begun. In the present study, qRT-PCR was used to determine the expression of circ{sub 0}001649 in NSCLC tissues and cells. Its clinical significance was further assessed by Fisher's exact test, Kaplan-Meier analysis and Cox regression model. Additionally, loss-of-function and gain-of-function experiments were carried out to detect the functional role of circ{sub 0}001649 in cell proliferation, migration and invasion. Furthermore, animal study was performed to confirm the in vitro results. Importantly, luciferase reporter assay was induced to reveal the underlying mechanism of circ{sub 0}001649. As a result, circ{sub 0}001649 was decreased in NSCLC tissues and cells and this downregulation is correlated with advanced TNM stage, positive lymph node metastasis and unfavorable prognosis. Additionally, circ{sub 0}001649 inhibited cell growth and metastasis both in vitro and in vivo. In mechanism, circ{sub 0}001649 was identified as the sponge of miR-331-3p and miR-338-5p. Moreover, the biological functions of circ{sub 0}001649 is partly dependent on its regulation on miR-331-3p and miR-338-5p. Collectively, this study suggested that circ{sub 0}001649/miR-331-3p/miR-338-5p regulatory signaling might be a potential target for NSCLC therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog pathway factor Gli3

Although important progresses have been made in the diagnosis and treatment of bladder cancer (BCa), the overall survival for patients with advanced BCa remains poor. It is necessary to uncover the molecular mechanism underlying the initiation and progression of bladder cancer. According to previous reports, mircoRNAs (miRNAs) can regulate tumorigenesis by targeting their downstream mRNAs. This study aims to explore and analyze a novel miRNA-mRNA axis which can regulate the progression of bladder cancer. Based on the microarray analysis, 182 mRNAs were found to be upregulated in BCa tissues. Gene oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these upregulated mRNAs are related with hedgehog pathway. Gli3, an important factor of hedgehog pathway, belongs to these 182 upregulated mRNAs. Therefore, Gli3 was chosen to do further study. Kaplan-Meier analysis revealed that highly expressed Gli3 predicted unfavorable prognosis for patients with BCa. Results of functional experiments indicated the inhibitory effects of silenced Gli3 on cell proliferation, migration and EMT progress. Mechanically, Gli3 was the target mRNA of miR-7-5p in BCa cells. Finally, rescue assays were performed to validate the specific function of miR-7-5p/Gli3 axis in BCa progression. According to all data, we concluded that miR-7-5p acts as a tumor suppressor in BCa by downregulating Gli3.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

DDX5 promotes hepatocellular carcinoma tumorigenesis via Akt signaling pathway

The DEAD-box-protein DDX5 is an ATP-dependent RNA helicase and also acts as co-activator that contributes to progression and metastasis of various tumours. However, its expression as well as prognostic roles of DDX5 in hepatocellular carcinoma (HCC) remain elusive. In this study, we investigated clinical significance and biological functions of DDX5 in HCC. Our results suggested that DDX5 showed overexpression at both transcriptional and translational levels in HCC tissues compared with adjacent normal tissues. Moreover, DDX5 expression was demonstrated to be correlated with tumor size (p p = 0.013), M stage (p = 0.006), tumor differentiation (p p = 0.001). Simultaneously, high DDX5 expression was found to be significantly correlated to worse outcome including Disease free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.032) according to Kaplan-Meier survival analysis. In vitro studies, it suggested that knockdown of DDX5 suppressed HCC cells migration, invasion and epithelial -to- mesenchymal transition (EMT) process. Depletion of DDX5 could promote HCC cells growth. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that PI3K/Akt signaling pathway obtained the highest enrichment. Furthermore, we found that knockdown of DDX5 decreased Akt as well as p-Akt (S473) expressions. Collectively, these findings suggested that DDX5 facilitated HCC cells growth via Akt signaling pathway. DDX5 played a crucial role in HCC proliferation and tumorigenesis and may be a novel prognostic marker and potential therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

As an independent prognostic factor, USP6 promotes the invasion and metastasis of colon cancer

Highlights: • USP6 is highly expressed in colon cancer tissues at both mRNA and protein levels. • High USP6 expression was closely associated with the invasion and metastasis of colon cancer. • USP6 overexpression promotes colon cancer cell invasion and metastasis both in vitro and in vivo. • USP6 is considered as a novel gene in promoting the invasion and metastasis of colon cancer. The lack of efficient tumor invasion and metastatic biomarkers led to high mortality rates in colon cancer patients. Aberrant expression of ubiquitin-specific protease 6 (USP6) was involved in several diseases including cancer, while its role in the progression of colon cancer was still unclear. In this study, USP6 was evaluated at both mRNA and protein levels by using RT-PCR, western blot and immunohistochemistry staining analyses. The results revealed that high USP6 expression predicted poor disease-specific survival and overall survival through Kaplan-Meier analyses with log-rank tests, univariate and multivariate Cox analyses. Furthermore, cell function assay demonstrated that USP6 could promote colon cancer cells’ invasion in vitro and liver metastasis in vivo. These findings indicated that high USP6 expression contributed to the progression of colon cancer and USP6 may be a valuable prognostic factor in patients with colon cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Three differential expression profiles of miRNAs as potential biomarkers for lung adenocarcinoma

Highlights: • To identify the differential miRNAs expression between lung cancer and normal tissues. • Data analysis was based on a computational approach to detect survival-associated signatures. • Three-miRNA signature could be used as a prognostic marker in LACA. Owing to the poor prognosis, novel biomarkers for lung adenocarcinoma (LACA) are needed nowadays. The aim of the study was to identify the differential miRNAs expression between lung cancer and normal tissues and evaluate the prognostic values of the miRNAs. Multidimensional data of 528 samples were retrieved from The Cancer Genome Atlas archive. Data analysis was based on a computational approach to detect survival-associated molecular signatures. A total of 191 differentially expressed miRNAs were identified between LACA tissues and normal tissues, including 88 up-regulated and 103 down-regulated miRNAs. The Kaplan-Meier survival method revealed the prognostic function of the three miRNAs (miR-1293, miR-873 and miR-1914). Cox regression analysis showed that the three-miRNA signature was an independent prognostic factor in LACA. The functional enrichment analysis suggested that the target genes of three miRNAs may be involved in various pathways related to the cancer. This study demonstrated that the three-miRNA signature (miR-1293, miR-873 and miR-1914) could be used as a prognostic marker in LACA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Clinically applicable 53-Gene prognostic assay predicts chemotherapy benefit in gastric cancer: A multicenter study

BACKGROUND:We previously established a 53-gene prognostic signature for overall survival (OS) of gastric cancer patients. This retrospective multi-center study aimed to develop a clinically applicable gene expression detection assay and to investigate the prognostic value of this signature. METHODS:A TCGA gastric adenocarcinoma cohort (TCGA-STAD) was used for comparing 53-gene signature with other gene signatures. A high-throughput mRNA hybridization gene expression assay was developed to quantify the expression of 53-genes in formalin-fixed paraffin-embedded tissues of 540 patients enrolled from three hospitals. 180 patents were randomly selected from two hospitals to build a prognostic prediction model based on the 53-gene signature using leave-p-out (one-third out) cross-validation method together with Cox regression and Kaplan-Meier analysis, and the model was assessed on three validation cohorts. FINDINGS:In the evaluation phase, studies based on TCGA-STAD showed that the 53-gene signature was significantly superior to other three prognostic signatures and was independent of TCGA molecular subtypes and clinical factors. For clinical validation and utility, the prognostic scores were generated using the newly developed assay, which was reliable and sensitive, in 100 sampling training sets and were significantly associated with OS in 100 sampling validation sets. The scores were significantly associated with OS in three independent and combined validation cohorts, and in patients with stages II and III/IV. The multivariate Cox regression demonstrated that the prognostic power of the score was independent of clinical factors, consistent with those findings in the TCGA dataset. Finally, patients with good prognostic scores exhibited significantly a better 5-year OS rate from adjuvant FOLFOX chemotherapy after surgery than from other chemotherapies. INTERPRETATION:The 53-gene prognostic score system is clinically applicable for predicting the OS of patients independent of clinical factors in gastric cancers, which could also be a promising predictive biomarker for FOLFOX regimen. FUNDING:Chinese National Science and Technology, National Natural Science Foundation and Natural Science Foundation of Jiangsu Province.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Profiling overstory survival trends following varying thinning and burning disturbance regimes in a mixed pine-hardwood forest in the US South

Prescribed burning as a silvicultural tool may be effective for achieving various management objectives, yet some practitioners have concerns about inadvertently increasing overstory tree mortality. Using extensive data from a long-term, ongoing study in northcentral Alabama, USA, that systematically applies a variety of thinning and prescribed burning disturbances on mixed pine-hardwood stands, we assess survival trends for different groups of trees. The primary research question is whether more frequent prescribed burns adversely affects overstory survival versus infrequent or no burns; secondary questions explore whether overstory survival trends differ based on thinning level, species group, or size class. Interest is in broad groups of trees, not individual tree survival or mortality; consequently, survival analysis methods are used, including nonparametric Kaplan-Meier (KM) techniques for examining single grouping factors, and parametric accelerated failure time models for analyzing simultaneous effects of multiple covariates. Leveraging relatively recent methodological advances, the statistical techniques are adjusted for interval censored data. KM survival curves showed that more frequent prescribed fires did not result in differing survival trends. Also, trees in unthinned stands had the lowest 14-year survival compared to thinned stands, oaks had the highest survival compared to pines and the others species group, and the smallest size class of overstory trees had the lowest survival. In conclusion, these results support managing transitional mixed pine-hardwoods using thinning and multiple prescribed fires to restore specific species composition and structure.

54 ENVIRONMENTAL SCIENCES↗