Molecular profiles of appendiceal adenocarcinoma: The UCSD experience.

397 Background: Appendix cancer is rare, which precludes its study in randomized trials. As such, no evidence-based guidelines currently exist regarding the optimum systemic therapy for this disease entity. Typically, these patients are treated with regimens for colorectal carcinoma. Previous studies have shown high intra-tumoral mRNA levels of EGFR were significantly associated with response to irinotecan based chemotherapy, and that mucinous colorectal cancer overexpresses markers of resistance to 5-FU and oxaliplatin. We examined pharmacogenomics markers for appendiceal cancer and colon cancer to understand underlying similarities and differences between these tumor types. Methods: Intratumoral gene expression levels were assessed from paraffin-embedded tissue samples, using laser capture microdissection and quantitative real-time PCR from 69 colorectal and 34 appendiceal adenocarcinomas. A retrospective chart review was performed to correlate gene expression with overall survival. KRAS and BRAF mutational analyses and gene expression levels of ERCC1, TS, and EGFR were correlated with overall survival. Results: Appendiceal tumors had significantly higher expression of EGFR, (2.66 vs 1.4, p<.0001). No BRAF V600E mutations were found in the appendiceal tumors, incidence was 8.97% of the colon patients. UPDATE: In appendix cancer, KRAS mutations were noted in 65.5% of patients, there were no BRAF mutations. Median ERCC1, TS, EGFR, and VEGFR2A expression was 1.4, 1.21, 1.57, 2.19 respectively. Patients with metastatic appendiceal cancer had a significantly longer median OS than metastatic colon patients, (113 mo vs 43.9 mo, p = .0154). For appendiceal cancer patients, there was no significant correlation between any of the biomarkers and OS, although the sample size was underpowered for such an analysis. Conclusions: Metastatic appendiceal cancer patients have significantly better outcomes than metastatic colon cancer patients. Molecular analyses reveal significant differences between these tumor types. Further molecular study of appendiceal cancer is needed, as this study and others suggest fundamental differences in biology from colon cancer.

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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4040 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4040-4040 ◽

Cited By ~ 2

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]

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Clock Gene Expression Levels and Relationship With Clinical and Pathological Features in Colorectal Cancer Patients

Chronobiology International ◽

10.3109/07420528.2011.615182 ◽

2011 ◽

Vol 28 (10) ◽

pp. 841-851 ◽

Cited By ~ 76

Author(s):

G. Mazzoccoli ◽

A. Panza ◽

M. R. Valvano ◽

O. Palumbo ◽

M. Carella ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cancer Patients ◽

Clock Gene ◽

Pathological Features ◽

Expression Levels ◽

Clock Gene Expression ◽

Colorectal Cancer Patients ◽

Clinical And Pathological Features ◽

Gene Expression Levels

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Abstract PO-226: Gene expression levels correlation to colon cancer disparities amongst African and Caucasian American men

10.1158/1538-7755.disp21-po-226 ◽

2022 ◽

Author(s):

Darryl A. Sams ◽

Dana R. Marshall

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cancer Disparities ◽

Caucasian American ◽

Expression Levels ◽

Gene Expression Levels

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Aberrant Expression of the MLL5, BAALC, ID1, and WT1 Genes Is Associated with Higher Induction Mortality and Poorer Overall Survival in Acute Promyelocytic Leukemia Patients Treated with ATRA and Anthracycline-Based Chemotherapy: An International Consortium On Acute Promyelocytic Leukemia Study

Blood ◽

10.1182/blood.v120.21.1407.1407 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1407-1407

Author(s):

Antonio R Lucena-Araujo ◽

Rafael Henriques Jacomo ◽

Haesook T Kim ◽

Raul A Melo ◽

Rosane Bittencourt ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Board Of Directors ◽

Acute Promyelocytic Leukemia ◽

Outcome Prediction ◽

Promyelocytic Leukemia ◽

Advisory Committees ◽

Aberrant Expression ◽

Expression Levels ◽

Gene Expression Levels

Abstract Abstract 1407 Background: Aberrant expression of MLL5, BAALC, ID1, and WT1 genes is frequently associated with inferior outcome in cytogenetically normal acute myeloid leukemia patients (Damm et al. Blood 2011; 117(17):4561–8). The expression levels of these genes vary in patients with acute promyelocytic leukemia (APL), but the clinical significance of these findings remains unclear. Objective: (1) to determine if the gene expression levels of MLL5, BAALC, ID1, and WT1 are associated with clinical outcome of APL patients treated with ATRA and anthracycline-based chemotherapy, (2) to generate an integrative score (IS) based on these potential prognostic factors and clinical parameters and (3) to use this score for outcome prediction in APL. Design and Methods: One hundred and fifty APL patients (age, 15–73y) from seven different Brazilian institutions and treated according to the IC-APL protocol were included. The treatment schedule was identical to the PETHEMA-LPA 2005, except for the replacement of idarubicin by daunorubicin; ATRA treatment was initiated immediately in all cases in which the diagnosis of APL was suspected based on morphology. Gene expression profile was analyzed by Real-time PCR. Integer weights for the IS were derived from Cox proportional hazard model, using overall survival (OS) as outcome parameter. Hazard ratios (HR) for OS were calculated for each variable separately (Table 1). Variables with P<0.05 in univariate analyses were included in the model. Variables considered for the model inclusion consisted in 2 clinical (WBC counts, albumin levels) and 5 molecular markers (FLT3-ITD status and gene expression levels of MLL5, BAALC, ID1, and WT1). Other candidates, such as age, platelet count, gender, ECOG performance status, PML breakpoint and FAB subtype were not significant and not included in the score. The HR were converted to integer weights according to the following: variables with HR < 1 were excluded from analyses; variables with HR 3 1 and < 1.5 were assigned a weight of 1; variables with HR 3 1.5 and < 2.5 were assigned a weight of 2; variables with HR 3 2.5 were assigned a weight of 3. The final score was the sum of these integer weights. Based on maximally selected rank statistics, the scores were grouped into 3 risk-groups: 0–5 (low-IS), 6–9 (intermediate-IS), and > 9 (high-IS). Results: The integrative weights of variables analyzed are summarized in Table 1. The IS was modeled in 137 patients (median score: 6; range, 1–17). According to PETHEMA-GIMEMA relapse risk criteria, 22%, 23% and 70% of patients assigned in the low-IS (n=46), intermediate-IS (n=57) and high-IS (n=34) groups were deemed high-risk of relapse (P<0.001). Overall, 118 (86%) patients achieved CR; the remaining 19 patients (14%) experienced early death due to hemorrhage (n=12), therapy-related infection (n=6) and differentiation syndrome (n=1). Induction mortality was significantly higher in the high-IS group (low: 2%; intermediate: 15%; high: 26%) (P=0.001). CR was achieved in the low-, intermediate-, and high-IS group in 98%, 84%, and 73% of the patients, respectively (P=0.007). With a follow-up of 24 months among survivors, patients assigned in the high-IS group had a lower 2-y OS rate (63%) compared with those in the intermediate- (80%) and low-IS groups (97%; P<0.001). Eight relapses were recorded. The IS was not predictive of relapses (P=0.351). Conclusions: Our results suggest that MLL5, BAALC, ID1, and WT1 expression levels are associated with clinical outcome and that the IS may become a useful tool for outcome prediction in APL. Disclosures: Lo-Coco: Cephalon: Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees. Löwenberg:Skyline Diagnostics: Membership on an entity's Board of Directors or advisory committees.

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Development and Validation of a Novel 13-Genes Prognostic Model for Colon Cancer

10.21203/rs.3.rs-378434/v1 ◽

2021 ◽

Author(s):

Duo Yun ◽

Zhirong Yang

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prognostic Value ◽

Risk Model ◽

Malignant Tumors ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Pathway Enrichment

Abstract Colon cancer is one of the most common malignant tumors in the world. The purpose of this study is to explore the prognostic value of genes in colon cancer. After analyzing gene expression profiles, differential expressed genes between 39 normal tissues and 398 tumor tissues were identified from The Cancer Genome Atlas database. We use Cox and lasso regression to find genes related to prognosis. Through analysis, 13 genes were found to predict the overall survival of colon cancer patients. In addition, the external comparing of gene expression and the single prognostic gene survival analysis were made. Finally, pathway enrichment and mutation status of each gene were also analyzed. After a series of bioinformatics analysis, we select 13 survival-related signature and established a prognostic risk model based on these genes. The prognostic risk model was developed to comprehensively predict the overall survival of colon cancer patients. The prognostic value of the 13-genes (CLDN23,HAND1,IL23A,KLHL35,SIX2,UPK2,HOXC11,KRT6B,SRCIN1,TNNI3,TYRO3,MIR6835,LINC02474) related risk score for each colon cancer patent was calculated to predict the survival. Furthermore, five genes (SIX2 MIR6835 LINC02474 CLDN23 HOXC11) were significantly associated with overall survival (OS). The KEGG pathway enrichment results suggested that most of the pathways are related to the occurrence, metabolism, proliferation and invasion of the tumor cells. It was found that the expression of 13-genes signature can be used as prognostic indicator for colon cancer patients. The 13-genes signature predictive model may help clinicians provide a prognosis and personalized treatment for colon cancer patients.

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Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

International Journal of Molecular Sciences ◽

10.3390/ijms22168485 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8485

Author(s):

Iranzu Gómez de Segura ◽

Patricia Ahechu ◽

Javier Gómez-Ambrosi ◽

Amaia Rodríguez ◽

Beatriz Ramírez ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Extracellular Matrix ◽

Matrix Protein ◽

Extracellular Matrix Protein ◽

Mrna Levels ◽

Expression Levels ◽

The Impact ◽

Ht 29 ◽

Gene Expression Levels

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.

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Molecular detection of occult nodal metastases in esophageal adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4540 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4540-4540

Author(s):

I. Altomare ◽

A. Pennathur ◽

L. Xi ◽

W. E. Gooding ◽

V. R. Litle ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Lymph Nodes ◽

Esophageal Adenocarcinoma ◽

Molecular Analysis ◽

Expression Levels ◽

Qrt Pcr ◽

Positive Expression ◽

Disease Free ◽

Gene Expression Levels

4540 Introduction: Esophageal adenocarcinoma (EAC) is an aggressive malignancy whose incidence is on the rise. Approximately 40% of patients with N0 disease will recur after theoretically curative surgery, suggesting that in early stage disease, metastatic spread is often undetected by routine pathology. Molecular techniques may more accurately detect micrometastatic spread of EAC, but the correlation between molecular analysis of nodes and prognosis is unknown. Our lab has previously identified and validated 4 markers whose gene expression levels are able to distinguish benign nodes from nodes with metastatic EAC: CK19, CK20, CEA and TACSTD1. We used quantitative real-time RT-PCR to evaluate the expression of these 4 markers in lymph nodes from 68 N0 and 62 N1 EAC patients to see if molecular staging is predictive of a worse clinical outcome. Methods: RNA was isolated from 1456 lymph nodes obtained from 130 patients who underwent resection of EAC. QRT-PCR was used to analyze gene expression for each of the 4 markers. Relative expression of each marker was compared with expression in 53 benign esophageal lymph nodes previously analyzed. Results: Analysis of 778 lymph nodes from 68 pN0 patients identified 71 nodes (9%) from 30 patients (44%) which showed positive expression of at least one marker, indicating occult metastases (and molecular upstaging). Analysis of 678 lymph nodes from 62 pN1 patients revealed 141 nodes (21%) from 40 patients (65%) which had positive expression of at least one marker in nodes that were pathologically negative. In the pathologically positive nodes from N1 patients, there was an encouraging 88% concordance between pathological and molecular analysis. After a median follow-up of 2 years, 13 N0 patients had recurrence of their cancer. Gene expression levels of 3 of the 4 markers (CK20, CEA and TACSTD1) correlated with significantly worse disease-free and overall survival among these N0 patients, with p values <0.05. Conclusion: We have shown that QRT-PCR of 3 independent genetic markers is predictive of significantly worse disease-free and overall survival among node-negative EAC patients by identifying lymph nodes with occult metastatic disease. Further analysis will reveal if the N1 patients with molecularly positive lymph nodes had significantly worse outcomes as well. No significant financial relationships to disclose.

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Quantitative gene expression underlying 18f-fluorodeoxyglucose uptake in colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.653 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 653-653

Author(s):

Bodil E. Engelmann ◽

Tina Binderup ◽

Andreas Kjær ◽

Annika Loft ◽

Thomas A. Gerds ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Normal Colonic Mucosa ◽

Imaging Method ◽

Glucose Transporter 1 ◽

Expression Levels ◽

Pet Ct ◽

Gene Expression Levels

653 Background: Positron emission tomography (PET) with the glucose analogue 18F-fluorodeoxyglucose (FDG) is widely used in oncologic imaging. This study examines the molecular mechanism underlying the detection of colon cancer (CC) by FDG-PET. Methods: Pre-operative PET/CT scans and tissue samples from primary CC and surrounding normal mucosa were obtained from 42 patients. FDG uptake was quantified using maximal standardized uptake value (SUVmax). The expression of ki67, glucose transporter 1 (GLUT-1), hexokinase 1 (HK1), hexokinase 2 (HK2), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF1α) and carbonic anhydrase IX (CaIX) mRNA was examined by quantitative real time reverse transcriptase-polymerase chain reaction. Results: All primary tumours showed increased uptake of FDG. The mean SUVmax was 15.0 (range 5.3 – 37.8). No correlation was found between tumour size and SUVmax. Mean gene expression levels of GLUT1, HK2, ki67, HIF1α, VEGF and CaIX, but not HK1, were significantly higher in primary tumours than in surrounding normal colonic mucosa. Linear regressions pairing tumour SUVmax with gene expression levels showed significant correlations between SUVmax and HK2, ki67 and CaIX, respectively. Conclusions: These results confirm FDG PET/CT as a functional imaging method in CC, and that FDG accumulation reflects molecular events related to glycolysis, cell proliferation, hypoxia, but not angiogenesis.

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