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.
"RT-PCR, WB, IHC Ye et al. (2010) Cervical cancer Tissue HIWI IHC Liu et al. (2010b) Cervical cancer Tissue HILI IHC He et al. (2010) Cervical cancer HeLa HILI WB Lu et al. (2012) Colon cancer Tissue HIWI IHC Liu et al. (2012) Colorectal and other "
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: We aimed to evaluate whether elevated serum synuclein-gamma levels were of clinical significance as a serological marker in cancer diagnosis and monitoring. Methodology: Pre-treatment serum synuclein-gamma levels of patients with gastrointestinal and esophageal squamous cell carcinomas, benign disease and healthy controls were analyzed by a specific sandwich ELISA for synuclein-gamma. Results: Statistically significant differences in serum synuclein-gamma levels between patients with colorectal cancer, gastric adenocarcinomas, esophageal cancer and healthy individuals were observed (p<0.001). When a cut-off value for synuclein-gamma was determined at =4ng/mL by receiver operating characteristic curves, sensitivity and specificity were 16.4% and 97.7% in colorectal cancer, 23.0% and 99.3% in gastric adenocarcinomas, and 19.5% and 98.7% in esophageal cancer, respectively. Compared with carcinoembryonic antigen and carbohydrate antigen 19-9, synuclein-gamma was more sensitive in early detection of colorectal cancer (17.3% vs. 9.6% and 7.5%), gastric adenocarcinomas (20.6% vs. 0% and 3.2%) and esophageal cancer (22.2% vs. 3.4% and 0%), respectively. A combined analysis of the above markers yielded incremental positive rates compared with anyone alone. Conclusions: These results indicated that serum synuclein-gamma provided a promising diagnostic biomarker for early detection and was a complementary biomarker of carcinoembryonic antigen and/or CA19-9 in gastrointestinal and esophageal cancer.
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