Gene expression profiling (GEP) has significantly contributed to the elucidation of the molecular heterogeneity of multiple myeloma plasma cells (MMPC) and only recently it has been recommended for risk stratification. Prior to GEP MMPC need to be enriched resulting in an inability to immediately freeze bone marrow aspirates or use RNA stabilization reagents. As a result in multi-center MM trials sample processing delay due to shipping may be an important confounder of molecular analyses and risk stratification based on GEP data.

Differential Shannon entropy (DSE) and differential coefficient of variation (DCV) are effective metrics for the study of gene expression data. They can serve to augment differential expression (DE), and be applied in numerous settings whenever one seeks to measure differences in variability rather than mere differences in magnitude. A general purpose, easily accessible tool for DSE and DCV would help make these two metrics available to data scientists. Automated p value computations would additionally be useful, and are often easier to interpret than raw test statistic values alone.

Colorectal cancer (CRC) is one of the most common malignances worldwide. Metastasis is responsible for the rapid recurrence and poor prognosis of CRC. However, the underlying molecular mechanism of CRC metastasis remains largely unclear. In this study we purposed to investigate the expression and biological functions of miR-490-3p in CRC metastasis, as well as to identify its downstream target genes and influenced pathway.

Lung cancer is the leading cause of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 80% of all lung cancers. Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the deadliest cancer-related proteins and plays a pivotal role in the most aggressive and lethal human cancers, including lung adenocarcinoma where it represents one of the most frequently mutated oncogene. Although therapeutic progresses have made an impact over the last decade, median survival for patients with advanced lung cancer remains disappointing, with a 5-year worldwide survival rate of <15%. For more than 20 years it has been recognized that constitutively active signaling downstream of KRAS is a fundamental driver of lung tumorigenesis. However, years of pursuit have failed to yield a drug that can safely curb KRAS activity; up to now no approved therapies exist for KRAS-mutant NSCLC. The aim of this review is to discuss the current knowledge of KRAS-mutated NSCLC, touching upon KRAS clinical relevance as a prognostic and predictive biomarker, with an emphasis on novel therapeutic approaches for the treatment of KRAS-variant NSCLC.

Archival formalin-fixed paraffin-embedded (FFPE) cancer tissue samples are a readily available resource for microRNA (miRNA) biomarker identification. No established standard for reference miRNAs in FFPE tissue exists. We sought to identify stable reference miRNAs for normalization of miRNA expression in FFPE tissue samples from patients with colorectal (CRC) and pancreatic (PC) cancer and to quantify the variability associated with sample age and fixation.

To explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages II and III colon cancers.

To observe the histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by spermatogonial stem cell self-renewal key regulating gene Piwil2 (Piwil2-iCSC).

Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.

ATP-binding cassette (ABC) transporters make up a superfamily of transmembrane proteins that play a critical role in the development of drug resistance. This phenomenon is especially important in oncology, where superfamily member ABCG2 (also called BCRP - breast cancer resistance protein) is known to interact with dozens of anti-cancer agents that are ABCG2 substrates. In addition to the well-studied and well-reviewed list of cytotoxic and targeted agents that are substrates for the ABCG2 transporter, a growing body of work links ABCG2 to multiple photodynamic therapy (PDT) agents, and there is a limited body of evidence suggesting that ABCG2 may also play a role in resistance to radiation therapy. In addition, the focus of ABC transporter research in regards to therapeutic development has begun to shift in the past few years. The shift has been away from using pump inhibitors for reversing resistance, toward the development of therapeutic agents that are poor substrates for these efflux pump proteins. This approach may result in the development of drug regimens that circumvent ABC transporter-mediated resistance entirely. Here, it is our intention to review: 1) recent discoveries that further characterize the role of ABCG2 in oncology, and 2) advances in reversing and circumventing ABC transporter-mediated resistance to anti-cancer therapies.

Studies on expression of orexins (OXs) and their receptors in human prostate gland and human prostatic cell lines are scanty and their results contradictory. Regarding this, we carefully reinvestigated this problem on human prostatic cell lines.

Tumor associated macrophages are major inflammatory cells that play an important role in the tumor microenvironment. In this study, we investigated the prognostic significance of tumor associated macrophages (TAMs) in MSI-high gastric cancers using immunohistochemistry. CD68 and CD163 were used as markers for total infiltrating macrophages and M2-polarized macrophages, respectively. The density of CD68+ or CD163+ TAMs in four different areas (epithelial and stromal compartments of both the tumor center and invasive front) were analyzed in 143 cases of MSI-high advanced gastric cancers using a computerized image analysis system. Gastric cancers were scored as "0" or "1" in each area when the density of CD68+ and CD163+ TAMs was below or above the median value. Low density of CD68+ or CD163+ macrophages in four combined areas was closely associated with more frequent low-grade histology and the intestinal type tumor of the Lauren classification. In survival analysis, the low density of CD163+ TAMs was significantly associated with poor disease-free survival. In multivariate survival analysis, CD163+ TAMs in four combined areas, stromal and epithelial compartments of both tumor center and invasive front were independent prognostic indicator in MSI-high gastric cancers. In addition, the density of CD163+ TAMs correlated with tumor infiltrating lymphocytes (TILs). Our results indicate that the high density of CD163+ TAMs is an independent prognostic marker heralding prolonged disease-free survival and that the prognostic implication of CD163+ TAMs might be determined by the proportional balance of TAMs and TILs in MSI-high gastric cancers.

Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer.

The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.

In our previous study, we showed that miR-125a directly targeted a WT1 oncogene, which was overexpressed in leukemia and various kinds of solid tumors including lung, breast, gastric, and colon cancers, and brain tumors and was deeply involved in leukemogenesis and tumorigenesis and that miR-125a knockout mice overexpressed WT1 and developed myeloproliferative disease. It had been also reported that miR-125a is downregulated in leukemia and various types of solid tumors such as lung cancers, suggesting its tumor suppressor function. Therefore, it is important to elucidate what is target(s) of miR-125a for understandings of such functions although few target genes for it are known. In the present study, Zbtb7a oncogene was identified as a potential target for miR-125a by gene expression profiling in miR-125a knockout mice combined with bioinformatics target prediction. EGFP-3'UTR reporter assay showed that miR-125a suppressed Zbtb7a expression through its direct binding to the Zbtb7a-3'UTR. Zbtb7a knockdown by siRNA suppressed cell proliferation and induced G1 cell cycle arrest and apoptosis in lung cancer cells. Furthermore, miR-125a expression showed a negative correlation with Zbtb7a expression in non-small cell lung cancer tissues. The present study showed for the first time that Zbtb7a was a direct target for miR-125a and was involved in cell cycle progression and apoptosis of lung cancer cells. These results also demonstrated that deregulation of miR-125a-Zbtb7a signaling was associated with the development and progression of lung cancer. © 2015 Wiley Periodicals, Inc.

We attempted to elucidate the mechanism of cell death after radiation by studying how β-catenin silencing controls the radiation sensitivity of radioresistant head and neck cancer cells.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease affecting predominantly young women. Clinical symptoms of this progressive disease include dyspnoea, cough, recurrent pneumothorax, hemoptysis and chylothorax. LAM is generally aggressive in nature and ultimately results in respiratory failure. Important hallmark features of this metastatic disease include the formation of lesions of abnormal smooth muscle cells, cystic destruction of the lung tissue and lymphangiogenesis affecting the lungs, abdomen and lymphatics. Research over the last 10-15 years has significantly enhanced our understanding of the molecular and cellular processes associated with LAM. These processes include mutational inactivation of the tuberous sclerosis complex genes, TSC1 and TSC2, activation of the mammalian target of rapamycin (mTOR) pathway, enhanced cell proliferation and migration, lymphangiogenesis, metastatic spread through the blood and lymphatic circulations, sex steroid sensitivity and dysregulated autophagy. Despite this increased knowledge there is currently no cure for LAM and treatment options remain limited. Whilst the mTOR inhibitor rapamycin has shown some benefit in patients with LAM, with stabilisation of lung function and improved quality of life, cessation of treatment results in recurrence of the disease progression. This highlights the urgent need to identify novel targets and new treatment regimens. The focus of this review is to summarise our current understanding of the cellular and molecular processes associated with LAM and highlight emerging treatments.

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment.