Novel Prognostic Marker (novel + prognostic_marker)

Distribution by Scientific Domains

Selected Abstracts

Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3-year follow-up study

Panagiota Georgiadou
Eur J Clin Invest 2010; 40 (4): 288,293 Abstract Objectives, Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD). Methods, In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 225, maximum 39 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons. Results, Baseline lnOPN levels were directly related to age (r = 027, P < 0001) and inversely to left ventricular ejection fraction (r = ,032, P < 001). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (, = ,0013, P = 002). Median OPN value was 55 ng mL,1. In the univariate Cox-regression analysis, OPN levels > 55 ng mL,1 (n = 50) were significantly related to adverse cardiac outcome (HR = 240, 95% CI: 111,523, P = 0027). In multivariate model, OPN levels > 55 ng mL,1 remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 288, 95% CI: 109,758, P = 0032). Conclusion, OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD. [source]

Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence

Martin Spahn
Abstract Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was negatively correlated with the expression of the proto-oncogen c-kit in primary carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR-221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan,Meier estimates and Cox proportional hazard models showed that miR-221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa. [source]

Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer

THE PROSTATE, Issue 3 2006
Zheng Fu
Abstract BACKGROUND Diminished expression of Raf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is a metastasis suppressor gene. However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissue microarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. The Cox proportional-hazards model was used to adjust for covariates including Gleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS RKIP expression was low in approximately 5%, 48%, and 89%of non-neoplastic prostate, primary tumors and metastases, respectively. Low RKIP expression in primary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was <,10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P,<,0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P,<,0.001). CONCLUSION In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients. 2005 Wiley-Liss, Inc. [source]

Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma

APMIS, Issue 8 2009
Lee J, Kang WK, Park JO, Park SH, Park YS, Lim HY, Kim J, Kong J, Choi MG, Sohn TS, Noh JH, Bae JM, Kim S, Lim DH, Kim K-M, Park CK. Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma. APMIS 2009; 117: 598,606. There are no known reliable biomarkers which can predict poor clinical outcome following curative resection of gastric adenocarcinoma. Given the importance of signal transducer and activator of transcription 3 (STAT3) activation in carcinogenesis, we attempted to determine whether STAT3 activation is prognostic of survival in curatively resected gastric cancer patients. We analyzed 311 surgically resected gastric cancer specimens for STAT3 activation and its downstream molecules such as matrix metalloproteinase (MMP)-9, MMP-10, cyclin D1, survivin, vascular endothelial growth factor (VEGF)-C, and VEGFR-3 using immunohistochemical studies and assessed their correlation with clinical outcome. Using immunohistochemistry, 303 specimens were interpretable for pSTAT3tyr705 expression. The pSTAT3 was detected in 79 (26.1%) of 303 gastric cancers. Of the downstream molecules tested, STAT3 activation was significantly associated with MMP-9 and MMP-10 expressions. On univariate analyses, 5-year disease-free survival (DFS) and overall survival (OS) for the tumors with STAT3 activation were considerably poorer than for those without STAT3 activation with statistical significance (5-year DFS 58.2% vs 68.3%; pSTAT3(,) vs pSTAT3(+); p = 0.0223; 5-year OS 59.5% vs 70.5%; pSTAT3(,) vs pSTAT3(+); p = 0.0128). On multivariate analyses, STAT3 activation was independently associated with inferior DFS (p = 0.049, hazard ratio [HR] = 1.445, 95% CI, 1.025, 2.120) along with AJCC stage IIIA or IIIB (p = 0.004, HR = 1.708, 95% CI, 1.178, 2.475). The STAT3 activation was also strongly correlated with inferior OS (p = 0.042, HR = 1.506, 95% CI, 1.025, 2.213). Based on our data, pSTAT3tyr705 may be a novel prognostic marker for poorer clinical outcome following curative resection and adjuvant therapy in gastric cancer. The clinical impact of a STAT3-targeted agent should be investigated in gastric cancer patients. [source]

Chromosome 1p21 deletion is a novel prognostic marker in patients with multiple myeloma

Hong Chang
Summary The combination of fluorescence in situ hybridization with cytoplasmic light chain detection identified chromosome 1p21 deletion in 18 (20%) of 87 patients with multiple myeloma. 1p21 deletion was associated with higher serum calcium level, 13q deletion, and t(4;14). Patients with 1p21 deletions had a significantly shorter progression-free survival (PFS) (median 105 vs. 223 months, P = 00002) and shorter overall survival (OS) (median 339 months vs. not reached, P = 0002) than those without 1p21 deletions. On multivariate analysis, which included deletions of 13q, TP53, t(4;14) and CKS1B amplification, 1p21 deletion remained as an independent risk factor for PFS (P = 001) and OS (P = 004). [source]

Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer

CANCER SCIENCE, Issue 10 2010
Ken Konishi
Metastasis-associated gene C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. The aim of this study was to explore the expression and clinical relevance of C4.4A in colorectal cancer. By quantitative RT-PCR, 154 colorectal cancer tissues were examined for C4.4A mRNA. We examined 132 colorectal cancer tissues by immunohistochemistry using a new polyclonal antibody that recognizes the C4.4A protein C-terminus containing the glycosylphosphatidyl-inositol anchor signaling sequence. A significant difference in 5-year overall survival was found between samples with high and low expression of C4.4A mRNA (P = 0.0005). Immunohistochemistry showed strong membranous staining of C4.4A at the invasive front of colorectal cancer tumors and at the frontier of metastatic lesions to lymph node and lung. The membranous staining with enhanced intensity at the invasive front of the primary colorectal cancer (Type A: 34/132, 25.6%) was associated with depth of invasion (P = 0.033) and venous invasion (P = 0.003), and was a significant independent prognostic factor (5-year overall survival in the entire series [n = 132; P = 0.004] and disease-free survival in stage II and III colorectal cancers [n = 82; P = 0.003]). Moreover, Type A C4.4A expression was linked to shorter liver metastasis-free survival rate, lung metastasis-free survival rate, or hematogenous metastasis-free survival (P = 0.0279, P = 0.0061, and P = 0.0006, respectively). Our data indicate that expression of the C4.4A protein at the invasive front acts as a novel prognostic marker in colorectal cancer, possibly through invasion-related mechanisms. (Cancer Sci 2010) [source]

Characterization of SEZ6L2 cell-surface protein as a novel prognostic marker for lung cancer

CANCER SCIENCE, Issue 8 2006
Nobuhisa Ishikawa
To identify molecules that might serve as biomarkers or targets for development of novel molecular therapies, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays coupled with purification of tumor cells by laser microdissection. A gene encoding seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) protein, was chosen as a candidate for such molecule. Semi-quantitative RT-PCR and western-blot analyses documented increased expression of SEZ6L2 in the majority of primary lung cancers and lung-cancer cell lines examined. SEZ6L2 protein was proven to be present on the surface of lung-cancer cells by flow cytometrical analysis using anti-SEZ6L2 antibody. Immunohistochemical staining for tumor tissue microarray consisting of 440 archived lung-cancer specimens detected positive SEZ6L2 staining in 327 (78%) of 420 non-small cell lung cancers (NSCLCs) and 13 (65%) of 20 small-cell lung cancers (SCLCs) examined. Moreover, NSCLC patients whose tumors revealed a higher level of SEZ6L2 expression suffered shorter tumor-specific survival compared to those with no SEZ6L2 expression. These results indicate that SEZ6L2 should be a useful prognostic marker of lung cancers. (Cancer Sci 2006; 97: 737,745) [source]