Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma.

MicroRNAs (miRNAs) are important gene regulators, which are often deregulated in cancers. In this study, the authors analyzed the microRNAs profiles of 78 matched cancer/noncanerous liver tissues from HCC patients and 10 normal liver tissues and found that 69 miRNAs were differentially expressed between hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues (N). Then the expressions of 8 differentially expressed miRNAs were validated by real time RT PCR. The set of differentially expressed miRNAs could distinctly classify HCC, N and normal liver tissues (NL). Moreover, some of these differentially expressed miRNAs were related to the clinical factors of HCC patients. Most importantly, Kaplan-Meier estimates and the log-rank test showed that high expression of hsa-miR-125b was correlated with good survival of HCC patients (hazard ratio, 1.787, 95% confidence interval, 1.020-3.133, p = 0.043). The transfection assay showed that overexpression of miR-125b in HCC cell line could obviously suppress the cell growth and phosporylation of Akt. In conclusion, the authors have demonstrated the diagnostic miRNA profile for HCC, and for the first time, identified the miR-125b with predictive significance for HCC prognosis.

Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells.

Transforming growth factor-beta (TGF-beta) plays a dual and complex role in human cancer. In this report, we observe a specific set of MicroRNAs (miRNAs) changed in response to TGF-beta in human hepatocellular carcinoma (HCC) cells by miRNA microarray screening. A cluster of miRNA, miR-23a approximately 27a approximately 24, is induced in an early stage by TGF-beta in Huh-7 cells. Knockdown of Smad4, Smad2 or Smad3 expression by RNA interference can attenuate the response of miR-23a approximately 27a approximately 24 to TGF-beta addition, indicating that this induction is dependent on Smad pathway. We also explore that miR-23a approximately 27a approximately 24 can function as an antiapoptotic and proliferation-promoting factor in liver cancer cells. In addition, expression of this miRNA cluster is found to be remarkably upregulated in HCC tissues versus normal liver tissues. These findings suggest a novel, alternative mechanism through which TGF-beta could induce specific miRNA expression to escape from tumor-suppressive response in HCC cells.

[Low-dose spiral CT versus standard dose CT in detection of pulmonary metastasis from gestational trophoblastic tumor].

OBJECTIVE: The purpose of this study is to investigate whether low-dose spiral chest CT scan can replace standard-dose CT scan in detecting pulmonary metastases for patients with gestational trophoblastic tumor (GTT). METHODS: Totally, 34 GTT patients underwent 56 chest CT scans for the assessment of pulmonary metastasis. All patients received CT examination both at standard-dose (120 KV, 150 mAs, pitch 1, and a standard reconstruction algorithm) and low-dose CT (120 KV, 40 mAs, pitch 2, and a bone reconstruction algorithm) simultaneously each time. The images were interpreted by two radiologists independently. A metastasis by CT image was defined as a nodule within lung parenchyma that could not be attributed to a pulmonary vessel. The number of lesions detected at each dose protocol was recorded. The size of each lesion was measured and categorized as < 5 mm, 5 - 10 mm or > or = 10 mm. The differences in detection of the lesions between the standard- and low-dose CT protocols were compared using Wilconxon signed rank test. RESULTS: 1417 lesions were detected at the standard-dose, whereas 1214 lesions were found by low-dose CT. Lesions < 5 mm detected by low-dose CT were fewer than that detected by standard-dose CT (Z = -3.368, P = 0.000), though there was no statistically significant difference between the standard- and low-dose CT in detecting lesion > or = 5 mm (Z = -0.055, P = 0.957). Moreover, the risk score of the patients was not affected either. The sensitivity of low-dose CT was 69.16% for all size of lesions, 58.50% for < 5 mm, 87.07% for 5 - 10 mm, and 97.01% for > or = 10 mm. The positive predictive value for different sizes of lesion was 80.71% (all sizes), 73.82% (5 mm), 88.86% (5 - 10 mm), and 98.48% (> or = 10 mm), respectively. CONCLUSION: Low-dose chest CT can replace the standard-dose chest CT as a screening and follow-up examination to assess the change in pulmonary metastasis for patients with gestational trophoblastic tumor.

Large-scale cDNA transfection screening for genes related to cancer development and progression.

A large-scale assay was performed by transfecting 29,910 individual cDNA clones derived from human placenta, fetus, and normal liver tissues into human hepatoma cells and 22,926 cDNA clones into mouse NIH 3T3 cells. Based on the results of colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806 cDNA species (8,237 clones) were found to possess the ability of either stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895 clones) were unigenes of uncharacterized structure and function. A comprehensive analysis of the genes and the potential mechanisms for their involvement in the regulation of cell growth is provided. The genes were classified into four categories: I, genes related to the basic cellular mechanism for growth and survival; II, genes related to the cellular microenvironment; III, genes related to host-cell systemic regulation; and IV, genes of miscellaneous function. The extensive growth-regulatory activity of genes with such highly diversified functions suggests that cancer may be related to multiple levels of cellular and systemic controls. The present assay provides a direct genomewide functional screening method. It offers a better understanding of the basic machinery of oncogenesis, including previously undescribed systemic regulatory mechanisms, and also provides a tool for gene discovery with potential clinical applications.