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Abstract Background Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients. Methods Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS). Results Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line. Conclusions Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

Abstract Background Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo. Methods A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting. Results We identified sphingosine kinase 1 (SPHK1) as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P < 0.0001) and lymph node metastasis (P = 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P < 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR. Conclusion In summary, our data implicate SPHK1 in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.

Granular computing is an emerging computing paradigm of information processing. Rough set theory is a kind of models of granular computing and is used to deal with the vagueness and granularity in information systems. Covering-based rough set theory is one of the most important extensions of the classical Pawlak rough set theory. In the covering-based rough set theory, the covering lower and upper approximation operators are two basic concepts. The axiomatic characterizations of covering-based approximation operators guarantee the existence of coverings reproducing the operators, so the rough set axiomatic system is the foundation of the covering-based rough set theory. In this paper, we present a new covering upper approximation operator and explore the basic properties of the covering upper approximation operator to find an axiomatic set for characterizing the covering upper approximation operator. We also discuss the relationships between the covering upper approximation operator and three other covering upper approximation operators, compare the covering upper approximation operator with the other covering upper approximation operators by defining precision degrees and rough degrees, and present the necessary and sufficient conditions for the covering upper approximation operators to be identical. The results not only are beneficial to enrich the kinds of the covering rough sets, but also have theoretical and actual significance to covering rough sets. [ABSTRACT FROM AUTHOR]

Purpose: To detect the expression of programmed cell death-1 (PD-1) in peripheral blood T lymphocytes of patients with primary liver cancer and its effect on their prognosis., Methods: The medical records of 42 patients with primary liver cancer, 36 patients with chronic hepatitis B (CHB) and 38 healthy volunteers composed the liver cancer group, benign lesion group and control group, respectively. Fluorescence quantitative RT-PCR (qRT-PCR) was used for detecting the expression level of PD-1 mRNA in peripheral blood T lymphocytes of subjects in the three groups, and flow cytometry was used for detecting the positive expression of PD-l protein on the surface of T lymphocytes of subjects., Results: Patients in the control group and the benign lesion group had lower expression level of PD-1 mRNA than those in the liver cancer group (p<0.05). Patients in the control group had lower expression level of PD-1 mRNA than those in the benign lesion group (p<0.05). Patients in the control group and the benign lesion group had lower positive expression rate of PD-1 protein on the surface of T lymphocytes than those in the liver cancer group (p<0.05)., Conclusion: The expression of PD-1 in the peripheral blood was higher in patients with primary liver cancer. Patients in the PD-1 low expression group had significantly better prognosis than those in the PD-1 high expression group. PD-1 may be related to the occurrence and development of primary liver cancer and is worthy of further study.