NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients.

The risk of developing metastatic disease in breast cancer patients is traditionally predictable based on the number of positive axillary lymph nodes, complemented with additional clinicopathological factors. However, since lymph node-negative patients have a 20-30% probability of developing metastatic disease, lymph node information alone is insufficient to accurately assess individual risk. Molecular approaches, such as multigene expression panels, analyze a set of cancer-related genes that more accurately predict the early risk of metastasis and the treatment response. Here, we present N-Myc downstream-regulated gene 4 (NDRG4) epigenetic silencing as a mechanistic biomarker of metastasis in ductal invasive breast tumors. While aberrant NDRG4 DNA hypermethylation is significantly associated with the development of metastatic disease, downregulation of NDRG4 transcription and protein expression is functionally associated with enhanced lymph node adhesion and cell mobility. Here, we show that epigenetic silencing of NDRG4 modulates integrin signaling by assembling ß1-integrins into large punctate clusters at the leading edge of tumor cells to promote an "adhesive switch," decreasing cell adhesion to fibronectin and increasing cell adhesion and migration towards vitronectin, an important component of human lymph nodes. Taken together, our functional and clinical observations suggest that NDRG4 is a potential mechanistic biomarker in breast cancer that is functionally associated with metastatic disease.

Discrimination of prostate carcinoma from benign prostate tissue fragments in vitro by estimating the gross biochemical alterations through Raman spectroscopy.

Raman spectroscopy has been proposed for detecting biochemical alterations in prostate cancer (PrCa) compared to benign prostate tissue in in vitro fragments from surgery for diagnostic purposes. Freezer-stored fragments of human prostate tissues were unfrozen and submitted to Raman spectroscopy with a dispersive spectrometer (830-nm and 200-mW laser parameters, 30-s exposure time). Fragments were fixed and submitted to histopathology to grade PrCa according to Gleason score. A total of 160 spectra were taken from 32 samples (16 benign tissues and 16 PrCa tissues). The relative concentrations of selected biochemicals were estimated using a least-squares fitting model applied to the spectra of pure compounds and the tissue spectrum. A discrimination model was developed employing the most statistically relevant compounds with capability of separating PrCa from benign tissues. The fitting model revealed that actin, hemoglobin, elastin, phosphatidylcholine, and water are the most important biochemicals to discriminate prostate depending on the Gleason score. A discrimination based on Euclidean distance using the relative concentrations of phosphatidylcholine and water showed the higher accuracy of 74 % to discriminate PrCa from benign tissue. Raman spectroscopy is an analytical technique with possibility for identifying biochemical constitution of prostate and could be used for diagnostic purposes.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer.

BACKGROUND: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). METHODS: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. RESULTS: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). CONCLUSION: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.