Leukemic conversion involving RAS mutations of type 1 CALR-mutated primary myelofibrosis in a patient treated for HCV cirrhosis: a case report.

Somatic frameshift mutations in exon 9 of calreticulin (CALR) gene are recognized as disease drivers in primary myelofibrosis (PMF), one of the three classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Type 1/type 1-like CALR mutations particularly confer a favorable prognostic and survival advantage in PMF patients. We report an unusual case of PMF incidentally diagnosed in a 68-year-old woman known with hepatitis C virus (HCV) cirrhosis who developed a progressive painful splenomegaly, without anomalies in blood cell counts. While harboring a type 1 CALR mutation, the patient underwent a leukemic transformation in less than 1 year from diagnosis, with a lethal outcome. Analysis of paired DNA samples from chronic and leukemic phases by a targeted next-generation sequencing (NGS) panel and single-nucleotide polymorphism (SNP) microarray revealed that the leukemic clone developed from the CALR-mutated clone through the acquisition of genetic events in the RAS signaling pathway: an increased variant allele frequency of the germline NRAS Y64D mutation present in the chronic phase (via an acquired uniparental disomy of chromosome 1) and gaining NRAS G12D in the blast phase. SNP microarray analysis showed five clinically significant copy number losses at regions 7q22.1, 8q11.1-q11.21, 10p12.1-p11.22, 11p14.1-p11.2, and Xp11.4, revealing a complex karyotype already in the chronic phase. We discuss how additional mutations, detected by NGS, as well as HCV infection and antiviral therapy, might have negatively impacted this type 1 CALR-mutated PMF. We suggest that larger studies are required to determine if more careful monitoring would be needed in MPN patients also carrying HCV and receiving anti-HCV treatment.

Soluble PD-L1 as a diagnostic and prognostic biomarker in resectable gastric cancer patients.

BACKGROUND: In this study, we compared programmed death-ligand 1 (PD-L1) expression in primary tissue samples and its soluble form (sPD-L1) concentration in matched preoperative plasma samples from gastric cancer patients to understand the relationship between tissue and plasma PD-L1 expression and to determine its diagnostic and prognostic value. METHODS: PD-L1 expression in tissue was assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), and sPD-L1 concentration in plasma was quantified by ELISA. The levels of the CD274 gene, which encodes for PD-L1 protein, were examined as part of bulk tissue RNA-sequencing analyses. Additionally, we evaluated the association between sPD-L1 levels and various laboratory parameters, disease characteristics, and patient outcomes. RESULTS: GC patients had significantly higher levels of sPD-L1 in their plasma (71.69 pg/mL) compared to healthy controls (35.34 pg/mL) (p < 0.0001). Moreover, sPD-L1 levels were significantly correlated with tissue PD-L1 protein, CD274 mRNA expression, larger tumor size, advanced tumor stage, and lymph node metastasis. Elevated sPD-L1 levels (> 103.5 ng/mL) were associated with poor overall survival (HR = 2.16, 95%CI 1.15-4.08, p = 0.017). Furthermore, intratumoral neutrophil and dendritic cell levels were directly correlated with plasma sPD-L1 concentration in the GC patients. CONCLUSIONS: sPD-L1 was readily measurable in GC patients, and its level was associated with GC tissue PD-L1 expression, greater inflammatory cell infiltration, disease progression, and survival. Thus, sPD-L1 may be a useful minimally invasive diagnostic and prognostic biomarker in GC patients.

Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation-migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure.

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer.

Despite advances in cancer detection and therapy, it has been estimated that the incidence of cancers will increase, while the mortality rate will continue to remain high, a fact explained by the large number of patients diagnosed in advanced stages when therapy is often useless. Therefore, it is necessary to invest knowledge and resources in the development of new non-invasive biomarkers for the early detection of cancer and new therapeutic targets for better health management. In this review, we provided an overview on the collagen family as promising biomarkers and on how they may be exploited as therapeutic targets in cancer. The collagen family tridimensional structure, organization, and functions are very complex, being in a tight relationship with the extracellular matrix, tumor, and immune microenvironment. Moreover, accumulating evidence underlines the role of collagens in promoting tumor growth and creating a permissive tumor microenvironment for metastatic dissemination. Knowledge of the molecular basis of these interactions may help in cancer diagnosis and prognosis, in overcoming chemoresistance, and in providing new targets for cancer therapies.

Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis.

Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN (p = 8 × 10-12), THBS2 (p = 1.2 × 10-6), CTHRC1 (p = 1.1 × 10-4), SULF1 (p = 3.8 × 10-4), COL5A1 (p = 1.3 × 10-4), COL10A1 (p = 5.7 × 10-4), COL12A1 (p = 2 × 10-3) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (p-value range 4.82 × 10-7-1.63 × 10-13). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets.

Kinetics and persistence of cellular and humoral immune responses to SARS-CoV-2 vaccine in healthcare workers with or without prior COVID-19.

SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.

Clinical Applications of Liquid Biopsy in Gastric Cancer.

Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, offering a less invasive and more convenient approach to obtain a time-point image of the tumor burden and its genomic profile. Samples collected from several body fluids, mostly blood, can be used to gain access to circulating tumor cells and DNA, non-coding RNAs, microRNAs, and exosomes, at any moment, offering a dynamic picture of the tumor. For patients with GC, the use of blood-based biopsies may be particularly beneficial since tissue biopsies are difficult to obtain and cause real distress to the patient. With advantages such as repeatability and minimal invasion, it is no wonder that the field of liquid biopsy has received tremendous attention. However, the abundance of studies, involving a wide range of assays with different principles, prevented for the moment the reproducibility of the results and therefore the translation into the clinic of liquid biopsy. In this review, we present the latest technical development and data on circulating biomarkers available through liquid biopsy in gastric cancer with an emphasis on their clinical utility in areas such as cancer screening, prognostic stratification, and therapeutic management.

High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) remains an aggressive malignancy with a high rate of mortality, being the third leading cause of cancer-related death. More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018. GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients. The discovery of new biomarkers useful in the early diagnosis of GC is mandatory. AIM: To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. METHODS: Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1. Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue. The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients. Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. RESULTS: Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue (P < 0.05). COL10A1 seems to show an elevated expression from the beginning of carcinogenesis, in the early stages, and its increased level remains elevated during cancer progression. A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified. Moreover, increased COL10A1 plasma level was associated with poor survival of the patients. Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve (AUC) of 0.9171 (P = 0.0002), sensitivity of 87.76%, and specificity of 100.0%. Furthermore, this study demonstrated the potential role of plasma COL10A1 in the early detection of GC, as in the early stage, we obtained an AUC of 0.8789 (P = 0.0030), sensitivity of 81.25%, and specificity of 100.0%. CONCLUSION: Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

Gastrointestinal cancer stem cells as targets for innovative immunotherapy.

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells (GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies, recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system. Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio- or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.

Inflammation-Related Patterns in the Clinical Staging and Severity Assessment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2-4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers' expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

Recent advances in gastric cancer early diagnosis.

Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

Angiogenesis in cutaneous T-cell lymphoma - proteomic approaches.

Neoangiogenesis plays an important role in cutaneous lymphoma pathogenesis. Cutaneous T-cell lymphoma (CTCL) is characterized by the presence of malignant T-cell clones in the skin. Vascular microenvironment of lymphomas accelerates neoangiogenesis through several factors released by tumoral cells: VEGF family, bFGF and PIGF. Tumor stroma (fibroblasts, inflammatory and immune cells) also plays a crucial role, by providing additional angiogenic factors. The angiogenic process through the VEGF-VEGFR axis can promote survival, proliferation and metastasis via autocrine mechanisms in cutaneous lymphomas. Microvascular density (MVD) measures the neo-vascularization of cutaneous lymphoma, generated by the response of tumor cells, proangiogenic stromal cells, and benign T/B lymphocytes within the tumor inflammatory infiltrate. Pro-angiogenic proteins have been found to indicate the evolution and prognosis in patients with CTCL. In conclusion, anti-angiogenic therapeutic protocols can target tumor vasculature or malignant tumor cells directly or through a large number of combinations with other drugs. The integration of proteomics into clinical practice based on high-throughput technologies leads to the development of personalized medicine, adapting the specific biomarkers to the application of cancer-type specific individual drug targets.

Inflammation-Related Mechanisms in Chronic Kidney Disease Prediction, Progression, and Outcome.

Persistent, low-grade inflammation is now considered a hallmark feature of chronic kidney disease (CKD), being involved in the development of all-cause mortality of these patients. Although substantial improvements have been made in clinical care, CKD remains a major public health burden, affecting 10-15% of the population, and its prevalence is constantly growing. Due to its insidious nature, CKD is rarely diagnosed in early stages, and once developed, its progression is unfortunately irreversible. There are many factors that contribute to the setting of the inflammatory status in CKD, including increased production of proinflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, altered metabolism of adipose tissue, and last but not least, gut microbiota dysbiosis, an underestimated source of microinflammation. In this scenario, a huge step forward was made by the increasing progression of omics approaches, specially designed for identification of biomarkers useful for early diagnostic and follow-up. Recent omics advances could provide novel insights in deciphering the disease pathophysiology; thus, identification of circulating biomarker panels using state-of-the-art proteomic technologies could improve CKD early diagnosis, monitoring, and prognostics. This review aims to summarize the recent knowledge regarding the relationship between inflammation and CKD, highlighting the current proteomic approaches, as well as the inflammasomes and gut microbiota dysbiosis involvement in the setting of CKD, culminating with the troubling bidirectional connection between CKD and renal malignancy, raised on the background of an inflammatory condition.

Long non-coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma.

Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non-coding RNAs (lncRNAs) and their main representatives, large intergenic non-coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem-like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs-induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

Murine models based on acute myeloid leukemia-initiating stem cells xenografting.

Acute myeloid leukemia (AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells (LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to introduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.

Increased Dkk-1 plasma levels may discriminate disease subtypes in myeloproliferative neoplasms.

Alterations in the bone marrow niche induced by abnormal production of cytokines and other soluble factors have been associated with disease progression in classical BCR-ABL1 negative myeloproliferative neoplasms (MPN). Variations in circulating proteins might reflect local disease processes and plasma proteome profiling could serve to identify possible diagnostic and prognostic biomarkers. We employed a human cytokine array to screen for 105 distinct analytes in pooled plasma samples obtained from untreated young MPN patients (<35 years) with different clinical phenotypes and driver mutations, as well as from healthy individuals. Among molecules that exhibited significantly increased levels in MPN patients versus controls, the top of the list was represented by Dickkopf-related protein 1 (Dkk-1), which also showed the highest potential for discrimination between MPN subtypes. In the next step, a quantitative ELISA was used to measure plasma Dkk-1 levels in 30 young-onset MPN-10 essential thrombocythemia (ET), 10 polycythemia vera (PV), 10 pre-fibrotic primary myelofibrosis (pre-PMF)-and 10 controls. The results suggested that plasma Dkk-1 levels could differentiate ET from pre-PMF, in JAK2 V617F-positive as well as in CALR-positive patients, and also ET from PV in JAK2 V617F-positive patients.

New therapeutic options opened by the molecular classification of gastric cancer.

Gastric cancer (GC) is one of the most lethal and aggressive cancers, being the third cause of cancer related death worldwide. Even with radical gastrectomy and the latest generation of molecular chemotherapeutics, the numbers of recurrence and mortality remains high. This is due to its biological heterogeneity based on the interaction between multiple factors, from genomic to environmental factors, diet or infections with various pathogens. Therefore, understanding the molecular characteristics at a genomic level is critical to develop new treatment strategies. Recent advances in GC molecular classification provide the unique opportunity to improve GC therapy by exploiting the biomarkers and developing novel targeted therapy specific to each subtype. This article highlights the molecular characteristics of each subtype of gastric cancer that could be considered in shaping a therapeutic decision, and also presents the completed and ongoing clinical trials addressed to those targets. The implementation of the novel molecular classification system will allow a preliminary patient selection for clinical trials, a mandatory issue if it is desired to test the efficacy of a certain inhibitor to the given target. This will represent a substantial advance as well as a powerful tool for targeted therapy. Nevertheless, translating the scientific results into new personalized treatment opportunities is needed in order to improve clinical care, the survival and quality of life of patients with GC.

Knockdown of KRT17 by siRNA induces antitumoral effects on gastric cancer cells.

BACKGROUND: Keratin 17 (KRT17) was shown to be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of various cancer types. Our previous studies identified KRT17 as a possible biomarker for gastric cancer by gene microarray, with an elevated expression that occurred early during tumorigenesis and increased during tumor progression. Based on these findings, we aimed to investigate KRT17 biological functions in gastric adenocarcinoma and its possible use as a rational molecular target for anticancer therapy. METHODS: We used RNA interference-mediated knockdown of KRT17 expression and analyzed the effects on cell proliferation, cell migration, and signal transduction in two gastric cell lines (AGS and NCI-N87) in vitro and on xenograft growth in vivo. RESULTS: The functional analysis of KRT17 knockdown cell lines showed a decreased cell proliferation (with 42.36% ± 3.2%) and migration ability (with 37.2% ± 6.2%) relative to scrambled siRNA control. The in vivo tumorigenicity on nude mice exhibited a significant decrease in tumor weight with 69.14% in xenografts obtained from AGS cells and 84.43% in xeno-NCI-N87 tumors. The analysis on KRT17 knockdown outcome on intracellular signaling identifies AKT/mTOR as the main affected pathway that sustains proliferation and survival, and also the AMPKα1/CREB pathway that was recently shown to induce organ protection and antiinflammatory response. CONCLUSIONS: Our results highlight KRT17 as a possible biomarker in gastric cancer promoting tumor growth, motility, and invasion, and suggest that KRT17 can be a valuable molecular target for development of anti-gastric cancer-specific therapies.

Prostate cancer proteomics: Current trends and future perspectives for biomarker discovery.

The clinical and fundamental research in prostate cancer - the most common urological cancer in men - is currently entering the proteomic and genomic era. The focus has switched from one single marker (PSA) to panels of biomarkers (including proteins involved in ribosomal function and heat shock proteins). Novel genetic markers (such as Transmembrane protease serine 2 (TMPRSS2)-ERG fusion gene mRNA) or prostate cancer gene 3 (PCA3) had already entered the clinical practice, raising the question whether subsequent protein changes impact the evolution of the disease and the response to treatment. Proteomic technologies such as MALDI-MS, SELDI-MS, i-TRAQ allow a qualitative/quantitative analysis of the proteome variations, in both serum and tumor tissue. A new trend in prostate cancer research is proteomic analysis of prostasomes (prostate-specific exosomes), for the discovery of new biomarkers. This paper provides an update of novel clinical tests used in research and clinical diagnostic, as well as of potential tissue or fluid biomarkers provided by extensive proteomic research data.