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.
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ABSTRACT: PIWI proteins, a subclade of the Argonaute family proteins, are expressed predominantly in the germline and bind to PIWI-interacting RNAs (piRNAs), which are 25-31 nucleotides in length. The PIWI/piRNA pathway plays critical roles in germline development by regulating transposons and other targets to maintain genome integrity. While the functions of PIWI in the germline have been extensively investigated, recent studies have accumulated evidence that the human PIWI proteins, HIWI and HILI, are aberrantly expressed in a variety of cancers. This review summarizes our knowledge of PIWI expression in cancer and discusses its possible role in tumorigenesis.Frontiers in Genetics 10/2012; 3:204. DOI:10.3389/fgene.2012.00204
- American Journal Of Pathology 04/2012; 180(6):2205-7. DOI:10.1016/j.ajpath.2012.04.001 · 4.60 Impact Factor
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ABSTRACT: PIWI proteins belong to the Argonaute family. The human PIWI subfamily genes encode four PIWI (also known as PIWI-like) proteins: PIWIL1, PIWIL2, PIWIL3, and PIWIL4. The dysregulated expression of PIWI proteins appears to be associated with tumorigenesis. To explore the expression of PIWI proteins in primary and metastatic tumors from patients with stage III epithelial ovarian cancer (EOC), evaluate the diagnostic value of PIWI in various tissues, and analyze the characteristics of each PIWI protein associated with metastasis. A total of 20 patients with stage III EOC were retrieved for the present study. Various tissues from the primary tumor, adjacent normal tissue, peritoneal metastasis, and lymph node with or without metastasis were examined. PIWI proteins were detected by immunohistochemistry using tissue microarray and analyzed. PIWIL1, PIWIL2, PlWlL3, and PIWIL4 were expressed in EOC. By comparison with the adjacent normal tissues, the expression of four PIWI proteins was significantly enhanced in the primary tumor and metastatic tissues (P< 0.01). PIWI proteins are upregulated in EOC and associated with metastasis. These proteins may be useful as diagnostic biomarkers for EOC. The function of PIWI proteins in EOC with tumor metastasis will need to be further explored.Cancer biomarkers: section A of Disease markers 01/2013; 13(5):315-21. DOI:10.3233/CBM-130360 · 1.19 Impact Factor