Heparanase and Survivin—potential markers of aggressiveness of colon cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14524-14524
Author(s):  
A. C. Hoffmann ◽  
C. Hoffmann ◽  
K. D. Danenberg ◽  
H. J. Lenz ◽  
P. V. Danenberg
Keyword(s):  
Gene Expression ◽  
Liver Metastasis ◽  
Decision Tree ◽  
Cancer Metastasis ◽  
Decision Tree Analysis ◽  
Tissue Samples ◽  
Tree Analysis ◽  
Expression Levels ◽  
Colon Cancers ◽  
Gene Expression Levels

14524 Background: Survivin is an inhibitor of apoptosis and specifically expressed in several human cancers. Heparanase seems to play an important role in cancer metastasis, angiogenesis and regulation of COX-2 expression. The purpose of this pilot study was to evaluate whether there is a difference in the level of survivin and heparanase expression in paraffin-embedded tissue from patients with colon cancer with and without metastasis. Methods: Paraffin-embedded tissue samples were obtained from 32 patients with primary colon tumors with (n = 15) and without liver metastases (n = 17) at the time of diagnosis. After laser capture microdissection direct quantitative real-time reverse transcriptase PCR (RT-PCR, TaqMan™) assays were performed in triplicates to determine survivin and heparanase gene expression levels. Gene expression was normalized with beta-Actin. Decision tree analysis was used to assess whether higher levels of these genes are associated with the existence of metastasis. Results: Neither survivin nor heparanase gene expression alone showed a significant relationship with the pM-Stage, although the detection levels of heparanase showed a tendency towards significant correlation with the existence of liver metastasis (p = 0.06). Decision tree analysis was used to split patients into two groups based on cut-off values of gene expression most closely associated with the pM-stage. The groupings determined by this analysis were significantly differently correlated with metastasis by Spearman’s test (p=0.03). Conclusions: Our results show that high expression levels of both survivin and heparanase in paraffin- embedded tissue are significantly correlated with the pM-Stage in this patient cohort. In conclusion, using intratumoral survivin and heparanase gene expression levels might be useful to identify patients at risk for liver metastasis. Prospective and larger clinical studies are warranted to validate our preliminary findings. No significant financial relationships to disclose.

scholarly journals HOXB9 Expression Correlates with Histological Grade and Prognosis in LSCC

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Chuanhui Sun ◽  
Changsong Han ◽  
Peng Wang ◽  
Yinji Jin ◽  
Yanan Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Histological Grade ◽  
Clinicopathological Features ◽  
Tissue Samples ◽  
Hox Gene ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Upregulated Genes ◽  
Gene Expression Levels

The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P<0.001). HOXB9 was found to correlate with histological grade (P<0.01) and prognosis (P<0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients.

scholarly journals Stratified time-course gene preselection shows a pre-diagnostic transcriptomic signal for metastasis in blood cells: a proof of concept from the NOWAC study

2017 ◽  
Author(s):  
Einar Holsbø ◽  
Vittorio Perduca ◽  
Lars Ailo Bongo ◽  
Eiliv Lund ◽  
Etienne Birmelé
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Cancer Metastasis ◽  
Screening Program ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Stable Gene ◽  
Expression Levels ◽  
Further Development ◽  
Gene Expression Levels

AbstractWe investigate whether there is information in gene expression levels in blood that predicts breast cancer metastasis. Our data comes from the NOWAC epidemiological cohort study where blood samples were provided at enrollment. This could be anywhere from years to weeks before any cancer diagnosis. When and if a cancer is diagnosed, it could be so in different ways: at a screening, between screenings, or in the clinic, outside of the screening program. To build predictive models we propose that variable selection should include followup time and stratify by detection method. We show by simulations that this improves the probability of selecting relevant predictor genes. We also demonstrate that it leads to improved predictions and more stable gene signatures in our data. There is some indication that blood gene expression levels hold predictive information about metastasis. With further development such information could be used for early detection of metastatic potential and as such aid in cancer treatment.

Genetic variants in R-Spondin/RNF43 complex and gene expression levels to predict efficacy of cetuximab (cet) in patients (pts) with metastatic colorectal cancer (mCRC): Data from the FIRE-3 phase III trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 190-190
Author(s):  
Francesca Battaglin ◽  
Yi Xiao ◽  
Joshua Millstein ◽  
Andreas Seeber ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Multivariable Analysis ◽  
Colorectal Carcinogenesis ◽  
Phase Iii ◽  
First Line ◽  
Tissue Samples ◽  
Expression Levels ◽  
The Impact ◽  
Gene Expression Levels

190 Background: Wnt signaling deregulation is a primary driver of colorectal carcinogenesis. RNF43 is a key suppressor of Wnt activation while R-Spodin inhibits RNF43 activity. RNF43 mutations are associated with the serrated neoplasia pathway, BRAF mutation and MSI. We hypothesized that genetic variants in the R-Spodin/RNF43 complex and corresponding genes expression levels may predict cetuximab efficacy in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in the randomized FIRE-3 trial was genotyped through the OncoArray, a custom array manufactured by Illumina. The impact on outcome of 17 functional SNPs within RNF43/ ZNRF3, LGR4/5 and RSPO1/2/3 was analyzed in 129 pts treated with first-line FOLFIRI/cet and 107 pts treated with FOLFIRI/bevacizumab (bev). Gene expression levels were measured from tumor tissue samples from 102 pts in the cet arm by HTG EdgeSeq Oncology Biomarker Panel. False discovery rate (FDR) for gene expression analysis was computed using the Benjamini-Hochberg approach (significant Q < 0.1). Results: In the cet cohort, pts with the C/C genotype of ZNRF3 rs132531 had significantly shorter overall survival compared to any T allele carriers (mOS: 20.3 vs 52 mo) in both univariable (HR 3.61, 95% CI 1.65-7.88, P < .001) and multivariable analysis (adjusted P = .01). Conversely, RSPO1 rs4652964 any G allele carriers showed increased tumor response (TR) rates compared to the A/A genotype (83 vs 66 %, P = .04). These associations were not observed in bev arm. Lower gene expression levels of RNF43 were associated with shorter PFS in pts with right-sided tumors receiving FOLFIRI/cet ( P = .006, Q < 0.1). RSPO1 expression levels were also associated with TR in the same subgroup (70 vs 10% in high vs low; P = .001, Q < .05). RNF43 expression was associated with TR in pts with left-sided tumors (82% in high vs 58% in low, P = .014, Q = 0.1). Conclusions: Our results provide the first evidence that germline polymorphisms and tumor gene expression levels of RNF43/ ZNRF3 and RSPO1 may have a predictive value in mCRC pts receiving first-line cetuximab-based treatment and contribute to modulate anti-EGFRs activity.

scholarly journals 5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis

2006 ◽  
Vol 119 (3) ◽  
pp. 522-526 ◽  
Author(s):  
Hidekazu Kuramochi ◽  
Kazuhiko Hayashi ◽  
Kazumi Uchida ◽  
Satoru Miyakura ◽  
Daisuke Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Related Gene ◽  
Primary Colorectal Cancer ◽  
Expression Levels ◽  
Gene Expression Levels

Transcriptional expression of survivin and its splice variants in cervical carcinomas

2007 ◽  
Vol 17 (5) ◽  
pp. 1092-1098 ◽  
Author(s):  
H. Futakuchi ◽  
M. Ueda ◽  
K. Kanda ◽  
K. Fujino ◽  
H. Yamaguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Splice Variants ◽  
Transcriptional Expression ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cervical Carcinomas ◽  
Significant Difference ◽  
Normal Controls ◽  
Gene Expression Levels

The objective of this study was to evaluate transcriptional expression of survivin and the two splice variants (survivin-2B and survivin-ΔEx3) in cervical carcinomas. The gene expression levels of survivin and its splice variants in 11 human cervical carcinoma cell lines and 20 malignant and 12 normal cervical tissue samples were analyzed using quantitative reverse transcription–polymerase chain reaction analysis. Gene expression levels of survivin and survivin-ΔEx3 in cell lines were higher than those in normal cervical tissues (P= 0.0193 and 0.0489). Transcript levels of survivin and survivin-ΔEx3 in carcinoma tissues were also higher than those in normal controls (P= 0.0016 and 0.0011). Gene expression levels of survivin and survivin-ΔEx3 in adenocarcinomas were statistically higher than those in squamous cell carcinomas (P= 0.0260 and 0.0487). There was no significant difference in survivin-2B gene expression between malignant and normal cervical samples or different histologic types. The ratios of survivin-2B/survivin and survivin-ΔEx3/survivin in carcinoma tissues were higher than those in normal controls (P= 0.0288 and 0.0081). Interestingly, the ratio of survivin-2B/survivin was increased in the patients with higher stages and with pelvic lymph node metastasis (P= 0.0205 and 0.0437), respectively. We conclude that survivin and its splice variants might be involved in the pathogenesis and development of cervical carcinomas.

scholarly journals Aromatase CYP19A1, progesterone receptor PGR and estrogen receptor ESR1 gene expression in biopsy specimens of endometrioid heterotopia and endometrial tissue by reverse transcription PCR

2019 ◽  
Vol 68 (2) ◽  
pp. 79-86
Author(s):  
Natalia Yu. Shved ◽  
Olga V. Malysheva ◽  
Natalia S. Osinovskaya ◽  
Arseniy S. Molotkov ◽  
Anna A. Tsypurdeyeva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Reverse Transcription ◽  
Comparison Group ◽  
Expression Level ◽  
Tissue Samples ◽  
Expression Levels ◽  
Esr1 Gene ◽  
Gene Expression Levels

Hypothesis/aims of study. Endometriosis is one of the most pressing problems of gynecology. Clarifying the expression of the estrogen receptor (ESR1) and the progesterone receptor (PGR) genes and polymorphisms in the aromatase (CYP19A1) gene in endometriosis will expand the understanding of the pathogenesis of the disease and the causes of resistance to its therapy. The objective of this study was to conduct a comparative analysis of mRNA expression of PGR, ESR1 and CYP19A1 genes in paired samples of the eutopic endometrium and peritoneal endometrioid lesions in order to search for predictive markers of response to hormonal therapy. In the future, this may allow personalizing the selection of hormonal preparations for the treatment of endometriosis. Study design, materials and methods. Reverse transcription real-time PCR made it possible to evaluate CYP19A1, PGR and ESR1 gene expression levels in studied tissue samples from 22 patients with endometriosis and 9 women in the comparison group. Results. Quantitative analysis revealed a high heterogeneity in the expression level of the studied genes, in both the endometrium and endometrioid lesions from patients with endometriosis. In the endometrium of patients in the comparison group, the heterogeneity of the expression level was observed only for the ESR1 gene. Conclusion. Our findings suggest a high variability in CYP19A1, ESR1 and PGR gene expression levels in the endometrium and peritoneal foci in patients with endometriosis. This information indicates the need for an individual approach to prescribing targeted therapy, since it is obvious that the effect of treatment will depend primarily on the availability of a therapeutic target in a particular patient. The absence of a typical expression pattern for each of the genes in patients with endometriosis indicates the heterogeneity of the disease and the need to develop a molecular classification of this common pathology.

Somatostatin receptor subtypes 1-5 gene expression in multiple sites in the same individual.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 182-182
Author(s):  
Michael Anthony Hall ◽  
Tanja Milosavljevic ◽  
Peter Casey ◽  
Catherine T. Anthony ◽  
Eugene Woltering
Keyword(s):  
Gene Expression ◽  
Liver Metastasis ◽  
Primary Tumor ◽  
Normal Tissue ◽  
Somatostatin Receptor ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Expression Levels ◽  
Somatostatin Receptor Subtypes ◽  
Gene Expression Levels

182 Background: Metastatic tumors may be fundamentally different than the primary tumor. This phenomenon may partially explain resistance of metastatic disease to therapy. We evaluated the gene expression levels of somatostatin receptor subtypes 1-5 (SSTR 1-5) in patients with disseminated neuroendocrine tumors (NETS) undergoing cytoreduction of their primary tumor and its nodal and liver metastasis. Methods: We compared the gene expression levels for SSTR 1-5 in primary tumor and their nodal and liver metastasis. The small bowel primary (SB), a mesenteric lymph node (LN) and a liver metastasis and their normal tissue counterparts were evaluated in four patients. RNA samples from each tissue underwent gene expression analysis using a customized Real Time Quantitative PCR (RT-qPCR) gene array. Normal tissue gene expression was compared to that obtained from the tumor sample at each site. Results: SSTR 2 was overexpressed (four-fold or greater, p≤ 0.01) compared to control levels in 8/12 (67%) specimens; 4/4 (100%) of the liver specimens, 3/4 (75%) of the SB specimens, and 1/4 (25%) of the LN specimens. SSTR 2 gene overexpression was not observed in all three tumor sites in any patient. No tumor had SSTR 2 downregulation. SSTR 5 was overexpressed (four-fold or greater, p≤ 0.01) compared to control levels in 6/12 (50%) specimens; 3/4 (75%) of the liver specimens, 2/4 (50%) of the SB specimens, and 1/4 (25%) of the LN specimens. SSTR 5 gene expression was up-regulated in all three tumor sites in one individual. SSTR 5 was down-regulated (7-fold, p<0.01) in one LN specimen. Changes in gene expression levels of SSTR 3 and SSTR 4 showed inconsistency between tumor sites, whereas that of SSTR1 was observed only at the metastatic sites. Conclusions: These results explain the observed variability in somatostatin receptor expression seen in 111In pentetreotide scans in multiple tumor sites from the same individual. The observation that gene expression varies from metastasis to metastasis may also help explain the difficulty in designing therapies that cure patients rather than inducing partial remissions.

Wt Kras and gene expression levels of VEGFR2, EGFR, and ERCC-1 associated with progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC) treated with first-line 5-FU or capecitabine with oxaliplatin and bevacizumab (FOLFOX/BV or XELOX/BV)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4056-4056
Author(s):  
A. B. El-Khoueiry ◽  
A. Pohl ◽  
K. Danenberg ◽  
J. Cooc ◽  
W. Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kras Mutation ◽  
Chemokine Receptors ◽  
Progression Free Survival ◽  
Vegf Receptor ◽  
First Line ◽  
Tissue Samples ◽  
Expression Levels ◽  
Kras Status ◽  
Gene Expression Levels

4056 Background: While wild type (wt) Kras is associated with improved outcome to anti-EGFR therapy in pts with mCRC, there are no identified predictors of outcome for FOLFOX/BV. We evaluated Kras status and expression of genes involved in angiogenesis, DNA repair and 5-FU metabolism in 68 patients treated with FOLFOX/BV or XELOX/BV. These genes included VEGF, VEGF-receptor 2 (KDR), Cox-2, IL 6 and 8, chemokine-receptors 1 & 2, EGFR and ERCC-1. Methods: Tissue samples from 68 patients with mCRC were analyzed. mRNA was extracted from laser-capture-microdissected tumor tissue. cDNA was prepared by reverse transcription and quantitation of the candidate genes was performed using a fluorescence- based real-time detection method (TaqMan). Allele specific RT-PCR was performed to determine Kras mutation status in codons 12 and 13. Results: There were 68 pts (38 males, 30 females), median age: 56 years (range 29–81). All received first line 5FU, oxaliplatin and BV (28 FOLFOX/BV, 40 XELOX/BV). Radiologic response: 1 CR, 39/68 (57%) PR, 27/68 (40%) SD, and 1 PD. Median OS is not reached. At a median follow-up of 32.0 months (mo) (range: 2.3–47.8 mo), the median PFS was 12.4 mo (95% CI: 9.8–15.2). Kras mutation was identified in 39 pts (57%). RR was 64% in pts with wt Kras and 52% in pts with mutant Kras (p=0.33). PFS was significantly longer for pts with wt kras compared to pts with mutant kras (13.7 mo [95% CI: 6.9–13.2] versus 8.3 mo [95%CI: 6.9–13.2], P=0.039). High EGFR (median PFS: 15.2 mo; 95% CI 11.7–16.5 mo), high VEGFR2 (median PFS: 13.9 mo; 95% CI 11.0–16.5 mo), and low ERCC1 (median PFS: 12.4 mo; 95% CI 10.9–16.4 mo) were associated with longer PFS compared to low EGFR (median PFS: 7.9 mo; 95% CI 6.9–11.0 mo, P=0.040), low VEGFR2 (median PFS: 7.2 mo; 95% CI 6.5–8.1 mo, P=0.032), and high ERCC1 (median PFS: 9.6 mo; 95% CI 5.8–15.2 mo, P=0.045). Conclusions: To our knowledge, this is the first report of a potential association between Kras status as well as gene expression levels of VEGFR2, ERCC-1 and EGFR and clinical outcome to FOLFOX/BV therapy in pts with mCRC. Prospective clinical trials are needed to validate these results. [Table: see text]

VEGF and VEGFR1 gene expression levels and tumor recurrence in adjuvant colon cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Y. Ning ◽  
G. Lurje ◽  
K. Danenberg ◽  
J. Cooc ◽  
D. Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Tissue Samples ◽  
Expression Levels ◽  
Stage Iii Colon Cancer ◽  
Gene Expression Levels

4040 Background: Tumor recurrence after curative resection is still a major problem in the management of adjuvant colon cancer, with recurrence rate approximately 30–40%. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. Our group previously showed that angiogenesis gene polymorphisms (VEGF and IL-8) may associated with tumor recurrence in adjuvant colon cancer (Lurje Ann Oncol, 2008). Here we tested the hypothesis whether gene expression levels of angiogenesis pathway (COX-2, EGFR, VEGF, VEGFR1, VEGFR2 and IL-8) could also predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Tissue samples from 140 adjuvant colon cancer patients (69 females and 71 males with a median age of 59 years; range=28–86) were available for gene expression assays. These tissue samples were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC) and LAC+USC medical center between 1999 and 2006. Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. mRNA was extracted from laser-capture-microdissected tumor tissue. After cDNA was prepared by reverse transcription, quantitation of the candidate genes and an internal reference gene (ß-actin) was performed using a fluorescence-based real-time detection method (TaqMan). Results: We found VEGF and VEGFR1 gene expression levels independently significantly associated with time to tumor recurrence in adjuvant colon cancer patients. Patients with lower VEGF gene expression and lower VEGFR1 gene expression levels had significantly longer time to tumor recurrence compared to those with higher VEGF and higher VEGFR1 gene expression levels (p<0.05, log-rank test). Conclusions: VEGF and VEGFR1 gene expression levels may predict tumor recurrence risk in adjuvant colon cancer patients. Our exploratory data warrant future confirmatory trial. [Table: see text]

scholarly journals FBN-1, FN-1 and TIMP-3 gene expression levels in patients with thoracic aortic aneurysm

2019 ◽  
Vol 45 (3) ◽  
pp. 263-270
Author(s):  
Hülya Özdemir ◽  
Sadrettin Pençe ◽  
Burcu Çaykara ◽  
Hani Alsaadoni ◽  
Ender Çoşkunpınar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aortic Aneurysm ◽  
Fasting Blood Glucose ◽  
Age At Onset ◽  
Rna Isolation ◽  
Aortic Aneurysms ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Tissue Samples ◽  
Expression Levels ◽  
Gene Expression Levels

AbstractBackgroundAortic aneurysm occurs in the thoracic and abdominal sections of the aorta and is a deadly late-age-at-onset disease. Thoracic aortic aneurysms (TTAs) are characterized by progressive smooth muscle cell rarefaction due to impaired extracellular matrix. The aim of this study was to investigate fibrillin-1 (FBN-1), fibronectin-1 (FN-1) and tissue inhibitors of metalloproteinases-3 (TIMP-3) gene expression levels in patients with TTA.Materials and methodsThe data were analyzed for 16 patients treated for TAA and nine control subjects. Tissue samples obtained during surgery were frozen immediately in liquid nitrogen and stored at −80°C until RNA isolation. Gene expression analysis was performed by quantitative reverse transcription polymerase chain reaction for each gene and Beta actin was used as control gene. 2−ΔΔCT method was used for the determining expression levels of the genes.ResultsAccording to the results of this study, TIMP-3 gene was nine-fold higher expressed in TAA tissues (p = 0.034). Furthermore, TIMP-3 expression levels were found associated with fasting blood glucose, red blood cells and ejection fraction. The gene expression levels of FBN-1 and FN-1 were not statistically significant (p > 0.05).ConclusionIn this clinical trial, we concluded that TIMP-3 expression increases in dilated aorta.

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