Hypoxia-Driven Gene Expression Is an Independent Prognostic Factor in Stage II and III Colon Cancer Patients

Abstract Background: 5-Fluoruracil based adjuvant chemotherapy after radical resection is recommended for stage II colon cancer patients with high risk of recurrence. Up to now, novel biomarkers still needed for better stratification for improving prognosis. Methods: Here we report that UCHL1 is an independent prognostic factor for stage II colon cancer patients and promotes chemoresistance both in vitro and in vivo. Results: Our study indicated that UCHL1 is significant up regulated in 96 pairs of stage II colon cancer patients who received postoperative 5-FU based chemotherapy. Stage II colon cancer patients with high UCHL1 expression showed high recurrence rate after chemotherapy. Multivariate Cox regression analysis showed that UCHL1 is an independent prognostic factor for overall survival (P=0.008) and disease-free survival (P=0.001). 5-FU based chemoresistance is examined in colon cancer cell lines (RKO and LoVo) with down regulation of UCHL1 by cytotoxicity test. Down regulation of UCHL1 exhibited decreased cell viability, elevated cell apoptosis rate, increased G2/M-phase and elevated level of cleaved caspase 3 and PARP when treated with 5-FU. Furthermore, the results in xenograft model are consistent with results in vitro.Conclusions: UCHL1 potentially contributing to identify recurrence risk and predict the benefit for postoperative 5-FU based adjuvant chemotherapy in stage II colon cancer patients.

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The size of retrieved lymph nodes correlates with the number of retrieved lymph nodes and is an independent prognostic factor in patients with stage II colon cancer

International Journal of Colorectal Disease ◽

10.1007/s00384-015-2357-9 ◽

2015 ◽

Vol 30 (12) ◽

pp. 1685-1693 ◽

Cited By ~ 9

Author(s):

Kazutake Okada ◽

Sotaro Sadahiro ◽

Toshiyuki Suzuki ◽

Akira Tanaka ◽

Gota Saito ◽

...

Keyword(s):

Colon Cancer ◽

Prognostic Factor ◽

Lymph Nodes ◽

Independent Prognostic Factor ◽

Stage Ii ◽

Stage Ii Colon Cancer

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Recurrence score distributions in stage II colon cancers of African American (AA) and Caucasian (CA) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.613 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 613-613 ◽

Cited By ~ 1

Author(s):

Rangaswamy Govindarajan ◽

James Posey ◽

Calvin Y. Chao ◽

Ruixiao Lu ◽

Trafina Jadhav ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cancer Patients ◽

Medical Center ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Recurrence Score ◽

Stage Ii ◽

Racial Groups ◽

Stage Ii Colon Cancer

613 Background: The 12-gene colon cancer assay (Oncotype DX) can identify groups of stage II colon cancer patients with lower or higher recurrence risk, but distribution of scores based on race/ethnicity has not been assessed. This study compared the distribution of Recurrence Score results and gene expression profiles between African American (AA) and Caucasian (CA) stage II colon cancer patients. Methods: Stage II colon cancer patients were identified from tumor registry data from four institutions: University of Arkansas for Medical Sciences, Little Rock; Veterans Administration Medical Center, Little Rock; Baptist Medical Center, Memphis, and University of Alabama at Birmingham. The 12-gene assay and mismatch repair (MMR) status were performed on formalin-fixed paraffin-embedded tissues by Genomic Health (Redwood City, CA). T-test and Wilcoxon test were used to compare data from the two groups (SAS Enterprise Guide 5.1). Results: Of the 244 subjects, there were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median ages (years) were 66 for AAs and 68 for CAs. Age, gender, surgery year, pathologic T-Stage, tumor location, number of nodes examined, lympho-vascular invasion, and MMR status were not significantly different between groups (p>0.05). Recurrence Score results between AAs (mean 27.9; SD 12.8) and CAs (mean 28.1; SD 11.8) were not statistically different (p>0.05). The proportion of patients with high Recurrence Score values (≥41) was similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups, (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC3 and GADD45B) was significantly different between the racial groups (p>0.05). After controlling for clinical and pathologic covariates, means and distributions of Recurrence Score and gene expression profiles still showed no statistical significance between racial groups (p>0.05). Conclusions: In a cohort of AA and CA stage II colon cancer patients with similar clinical characteristics, the distribution of Recurrence Score results and gene expression data were similar between AA and CA patients.

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Macroscopic tumor size as an independent prognostic factor for stage II/III gastric cancer patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1

Gastric Cancer ◽

10.1007/s10120-011-0038-0 ◽

2011 ◽

Vol 14 (3) ◽

pp. 274-278 ◽

Cited By ~ 19

Author(s):

Toru Aoyama ◽

Takaki Yoshikawa ◽

Takafumi Watanabe ◽

Tsutomu Hayashi ◽

Takashi Ogata ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Prognostic Factor ◽

Cancer Patients ◽

Tumor Size ◽

Independent Prognostic Factor ◽

Stage Ii ◽

D2 Gastrectomy ◽

Macroscopic Tumor ◽

Gastric Cancer Patients

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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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