Combined phenotype of 4 markers improves prognostic value of patients with colon cancer.
ABSTRACT Combination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens.
Immunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome.
With the tumor marker positive rate [32.0% (62/225) for SNCG; 76.9% (173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9% (252/407) for SNCG; 82.6% (336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN-), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN+).
Multimarker phenotypes improved tumor positive rate, detecting accuracy and prognostic value. In addition, a subgroup of more aggressive tumors can be identified by evaluating Hiwi level in LN- cancer, and SNCG level in LN+ cancer.
- SourceAvailable from: Kiichiroh Nakano[Show abstract] [Hide abstract]
ABSTRACT: Androgen receptors (ARs) are expressed in many breast cancer cells, but the mechanism of action of androgens is not as well-characterized as in other cell types. The study of microRNAs has recently provided with important insights into the biology of hormone-dependent cancer. We attempted to identify microRNAs induced by dihydrotestosterone in an AR-positive cell line. We examined a possible correlation among microRNAs, target genes, and ARs in breast cancer tissues using immunohistochemistry and laser capture microscopy. Our analysis demonstrated that miR-363 and its possible target IQ motif and WD repeats-1 (IQWD1) are involved in a microRNA-mRNA pathway related to the mechanism of action of androgens. Our analyses showed that a high tumor level of IQWD1 in patients with breast cancer was significantly associated with adverse clinical outcomes. Our findings indicated that the recruitment of IQWD1 to ARs may be a prerequisite for the growth stimulation by androgens through ARs in breast cancer cells.Anticancer research 11/2013; 33(11):4811-9. · 1.87 Impact Factor
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ABSTRACT: Cancer cells have countless behaviors of pluripotent embryonic stem cells and germ line cells, such as unlimited proliferation, self-renewal, and migration. Expression of specific germ line and embryonic genes in tumor cells may be associated with indefinite growth and invasiveness of such cells. Developmental pluripotency factor 2 (DPPA2) and HIWI are two important developmental genes which are involved in embryonic and germ line stem cell properties. Deciphering the role of these genes seems to be necessary for understanding cancer initiation and progression. Tumoral and normal tissues from 46 colorectal cancer (CRC) patients were subjected to gene expression analysis using quantitative real-time reverse transcription-polymerase chain reaction, prior to any therapeutic intervention. Overexpression of DPPA2 and HIWI was detected in 26.1 and 34.8 % of specimens, respectively. Significant correlation between DPPA2 overexpression and lymph node metastasis of the tumor cells (P = 0.049) was seen in the samples with advanced stages (III/IV) of the tumor development. HIWI mRNA expression was significantly associated to the depth of tumor invasion (P = 0.020) and the stage of tumorigenesis progression (P = 0.030). In samples with overexpression of at least one gene, DPPA2 mRNA expression was significantly correlated to the stage of tumor (P = 0.017). In the same samples, a significant correlation was observed between mRNA expression of HIWI and the stage of tumor cells (P = 0.034). These results documented the important role of HIWI and DPPA2 in tumorigenesis and also in lymph node metastasis of tumor cells. Further evaluation is required to uncover the detailed role of HIWI and DPPA2 and their interactions in tumorigenesis of CRC.Tumor Biology 02/2014; · 2.84 Impact Factor
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ABSTRACT: Combination of biomarkers may improve diagnosis and have better prognostic value than single markers. The purpose of this study was to investigate whether combined CEA and CD44v6 improves prognostic value in stage I and stage II (stage I/II) colorectal cancer (CRC). Preoperative serum CEA level and the expression of CD44v6 in CRC tissues were examined by electrochemiluminescence immunoassay and immunohistochemistry, respectively. The association of CEA and CD44v6 with clinicopathological features and their possible prognostic values was analyzed. The preoperative elevated serum CEA level and positive CD44v6 expression were detected in 30.1 % (52/173) serum samples and 60.5 % (101/167) CRC tissues, respectively. Patients with an elevated-CEA level or a CD44v6-negative tumor had a worse disease-specific survival (DSS) than those with a normal-CEA level or CD44v6-positive tumor (P = 0.024, P = 0.012, respectively). Moreover, CD44v6 expression could be used in discriminating patients from good to poor prognosis in normal-CEA subgroup (P = 0.043), but not in elevated-CEA subgroup (P = 0.563). Multivariate analysis revealed that combined CEA and CD44v6 was an independent prognostic factor for patients with stage I/II CRC (P = 0.023). However, serum CEA level only retained a borderline significance for correlation with a worse DSS (P = 0.059), and CD44v6 expression alone was not an independent prognostic factor for DSS in multivariate analysis (P = 0.123). These results suggested that combined CEA/CD44v6 had better prognostic value than CEA or CD44v6 alone for patients with stage I/II CRC.Clinical and Translational Oncology 07/2013; · 1.28 Impact Factor