Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition

Colorectal cancer is a leading form of cancer in both males and females. Early detection of individuals at risk of colorectal cancer allows proper treatment and management of the disease to be implemented, which can potentially reduce the burden of colorectal cancer incidence, morbidity and mortality. In recent years, the role of genetic susceptibility factors in mediating predisposition to colorectal cancer has become more and more apparent. Identification of high‐frequency, low‐penetrance genetic polymorphisms associated with the cancer has therefore emerged as an important approach which can potentially aid prediction of colorectal cancer risk. However, the overwhelming amount of genetic epidemiology data generated over the past decades has made it difficult for one to assimilate the information and determine the exact genetic polymorphisms that can potentially be used as biomarkers for colorectal cancer. This review comprehensively consolidates, based primarily on results from meta‐analyses, the recent progresses in the search of colorectal cancer‐associated genetic polymorphisms, and discusses the possible mechanisms involved.     

Permanent sensitive stain for choline-containing phospholipids on thin-layer chromatograms

The phosphomolybdic blue stain for choline of Levine and Chargaff can be used for detection of small amounts of choline-containing phospholipids on thin-layer chromatograms if they are first fixed with polyvinyl propionate to permit a washing step.     

MicroRNAs as potential investigative and predictive biomarkers in colorectal cancer

Colorectal cancer (CRC) is a noticeable reason of cancer-associated deaths with a high incidence and mortality rate. Countless effort have been put into the improving clinical management of CRC patients including more effective tools and a wide variety of biomarkers for diagnostic, prognostic or predictive purposes. In recent years, dysregulated miRNAs have been emerged as highly sensitive and specific markers to manage CRC in an effective way. They can play key roles in carcinogenesis as potential oncogenes, tumor suppressors or regulators of cancer network. Therefore, miRNAs may serve as molecular tools that can be quantified and used in diagnostic and prognostic approaches. Growing evidence also suggests that forced expression of tumor suppressor miRNAs or inhibiting the oncogene ones, can be used as a novel treatment strategy. In this review, we focus on the clinical applications of miRNAs as promising biomarkers of early cancer detection, prognosis and treatment.     

A panel of platelet-associated circulating long non-coding RNAs as potential biomarkers for colorectal cancer

Evidence has suggested the potential of tumor-educated platelets as a biomarker trove for cancer diagnostics, but the difficulty in isolation limits its application. Since most of the circulating RNAs are derived from platelets, the change of RNA profile in platelets may lead to altered RNA expression in serum. Here, we identified a panel of platelet-associated long non-coding RNAs (lncRNAs) and evaluated its diagnostic capacity in serum of colorectal cancer (CRC) patients. Four lncRNAs, LNCAROD, SNHG20, LINC00534, and TSPOAP-AS1, were upregulated in both platelets and serum of CRC patients. A binary logistic model derived from them has validated area under roc curve of 0.78 indicating great performance. Furthermore, the expression levels of LNCAROD and TSPOAP-AS1 were correlated with cancer staging and tumor location. Together, our results add novel lncRNA biomarkers to the list of blood tests for CRC diagnostics and provide molecular evidence for the cross-talk between CRC platelets and serum.     

Plasma antioxidant enzymes and clastogenic factors as possible biomarkers of colorectal cancer risk

Oxidative damage plays an important role in the pathogenesis of colorectal (CR) cancer. This study investigated the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione-S-transferase (GST) in plasma of 82 participants of a screening program for CR cancer prevention (30 females and 52 males; age 50-70 years). All subjects resulted positive to fecal occult blood test and were subsequently classified, according to the colonoscopy and histological findings, in patients with CR cancer, patients with colorectal polyps or controls. Furthermore, the activity of clastogenic factors (CFs) in plasma from study population was measured as the ability of inducing micronuclei (MN) in vitro in peripheral of a healthy donor. CAT and GR activities were significantly lower in CR cancer patients compared to controls (P<0.05) and polyps groups (P<0.05). SOD activity was significantly higher in patients with CR cancer than in polyp (P<0.05) and control (P<0.05) groups. GST activity was not significantly different in plasma of the three groups. An increase of CFs induction was observed in plasma of CR cancer patients (MN: 8.89±3.42) with respect to control (MN: 6.37±0.96 P<0.05). These results can contribute to define plasma biomarkers associated to oxidative stress damage that could predictive of CR cancer risk.     

Proteomic analysis of colorectal cancer: discovering novel biomarkers

Colorectal cancer is one of the most common cancers in the Western world. When detected at an early stage, the majority of cancers can be cured with current treatment modalities. However, most cancers present at an intermediate stage. The discovery of sensitive and specific biomarkers has the potential to improve preclinical diagnosis of primary and recurrent colorectal cancer, and holds the promise of prognostic and therapeutic application. Current biomarkers such as carcinoembryonic antigen lack sensitivity and specificity for general population screening. This review aims to highlight the role of current proteomic technologies in the discovery and validation of potential biomarkers with a view to translation to the clinic.     

Identification of biomarkers for colorectal cancer through proteomics-based approaches

The early detection of colorectal cancer is one of the great challenges in the battle against this disease. However, owing to its heterogeneous character, single markers are not likely to provide sufficient diagnostic power to be used in colorectal cancer population screens. This review provides an overview of recent studies aimed at the discovery of new diagnostic protein markers through proteomics-based approaches. It indicates that studies that start with the proteomic analysis of tumor tissue or tumor cell lines (near the source) have a high potential to yield novel and colorectal cancer-specific biomarkers. In the next step, the diagnostic accuracy of these candidate markers can be assessed by a targeted ELISA assay using serum from colorectal cancer patients and healthy controls. Instead, direct proteomic analysis of serum yields predominantly secondary markers composed of fragments of abundant serum proteins that may be associated with tumor-associated protease activity, and alternatively, immunoproteomic analysis of the serum antibody repertoire provides a valuable tool to identify the molecular imprint of colorectal cancer-associated antigens directly from patient serum samples. The latter approach also allows a relatively easy translation into targeted assays. Eventually, multimarker assays should be developed to reach a diagnostic accuracy that meets the stringent criteria for colorectal cancer screening at the population level.     

Noninvasive molecular biomarkers for the detection of colorectal cancer

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, noninvasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.     

Epigenetic biomarkers in colorectal cancer: premises and prospects

Context: Colorectal cancer is one of the most common cancers worldwide. Epigenetic alterations play an important role in the pathogenesis of the colorectal cancer.

Objective: This review has focused on the most recent investigations, which has suggested potential epigenetic biomarkers in colorectal cancer.

Methods: Evidences were achieved by searching online medical databases including Google scholar, Pubmed, Scopus and Science Direct.

Results: Extensive studies have indicated that aberrant epigenetic modifications could serve as potential biomarkers for diagnosis, prognosis and prediction of colorectal cancer.

Conclusion: Advances in aberrant epigenetic modifications can open new avenues for exploration of reliable and robust biomarkers to improve the management of CRC patients.     

Proteomic analysis of colorectal cancer: discovering novel biomarkers

Colorectal cancer is one of the most common cancers in the Western world. When detected at an early stage, the majority of cancers can be cured with current treatment modalities. However, most cancers present at an intermediate stage. The discovery of sensitive and specific biomarkers has the potential to improve preclinical diagnosis of primary and recurrent colorectal cancer, and holds the promise of prognostic and therapeutic application. Current biomarkers such as carcinoembryonic antigen lack sensitivity and specificity for general population screening. This review aims to highlight the role of current proteomic technologies in the discovery and validation of potential biomarkers with a view to translation to the clinic.     

Predictive and prognostic biomarkers in colorectal cancer

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in the United States.Three quarters of patients diagnosed with colorectal cancer will have early s...     

Immune cells: plastic players along colorectal cancer progression

Inflammatory cells are involved in tumour initiation and progression. In parallel, the adaptive immune response plays a key role in fighting tumour growth and dissemination. The double‐edged role of the immune system in solid tumours is well represented in colorectal cancer (CRC). The development and progression of CRC are affected by the interactions between the tumour and the host's response, occurring in a milieu named tumour microenvironment. The role of immune cells in human CRC is being unravelled and there is a strong interest in understanding their dynamics as to tumour promotion, immunosurveillance and immunoevasion. A better definition of immune infiltration would be important not only with respect to the ‘natural history’ of CRC, but in a clinically relevant perspective in the 21st century, with respect to its post‐surgical management, including chemotherapy responsiveness. While it is becoming established that the amount of tumour‐infiltrating lymphocytes influences the post‐surgical progression of early‐stage CRC, the relevance of this immune parameter as to chemotherapy responsiveness remains to be clarified. Despite recent experimental work supporting the notion that infiltrating immune cells may influence chemotherapy‐mediated tumour cell death, tumour‐infiltrating cells are not employed to identify patients who are more likely to benefit from adjuvant treatment. This review focuses on studies addressing the role of innate and adaptive immune cells along the occurrence and the progression of potentially curable CRC.     

Newer potential biomarkers in prostate cancer

Prostate-specific antigen (PSA) screening has led to a significant rise in the number of men diagnosed with prostate cancer and an associated increase in biopsies performed. Despite its limitations, including a positive predictive value of only 25%-40%, PSA remains the only generally accepted biomarker for prostate cancer. There is a need for better tools to not only identify men with prostate cancer, but also to recognize those with potentially lethal disease who will benefit from intervention. A great deal of work has been done worldwide to improve our knowledge of the genetics behind prostate cancer and the specificity of PSA by developing assays for different PSA isoforms. Common genetic alterations in prostate cancer patients have been identified, including CpG hypermethylation of GSPT1 and TMPRSS2:ERG gene fusion. Serum and urine detection of RNA biomarkers (eg, PCA3) and prostate cancer tissue protein antibodies (eg, EPCA) are being evaluated for detection and prognostic tools. This article reviews some of the promising developments in biomarkers.     

A proteomic profile of washing fluid from the colorectal tract to search for potential biomarkers of colon cancer

Washing fluid (WF) from the colon rectal tract after surgical resection might represent a first step in obtaining a mixture of proteins derived from the secretion of tumoral epithelial cells potentially involved in the pathological progression of tissue. In this study, we performed a proteomic analysis of colorectal WF to search for potential biomarkers of colon cancer. The outcome of this approach might open the possibility of using WF to screen for the precancerous and early stages of colorectal cancer (CRC). Samples of WFs were obtained during surgery from 35 patients submitted to colon resection for suspicious adenocarcinoma or carcinoma, while the respective controls were obtained by washing the healthy sections. WFs were immediately centrifuged, concentrated and trichloroacetic acid (TCA) was added to obtain protein pellets. After two-dimensional gel electrophoresis (2DE), the protein patterns of malignant samples were compared with respective normal samples. Forty-one protein spots were found to be differentially expressed exhibiting ≥2 fold-change of mean value spot intensities. After mass spectrometry, these protein spots collapsed into 38 different proteins. Interestingly, 19 of the differentially expressed proteins identified in the study corresponded to those suggested as being potential biomarkers of CRC. In accordance with the literature, these proteins showed the same direction of change (up or down for all proteins). Our results suggest that WF has the potential of being a method for the exploration of clinical samples for biomarker and drug target discovery.     

Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy

Introduction

Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication.

Objectives

We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration?≥?15 years.

Methods

A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics.

Results

For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC?=?0.739) and the ratio (AUC?=?0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses.

Conclusion

Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.

     

Proteins are potent biomarkers to detect colon cancer progression

Colon cancer is the most common type of cancer and major cause of death worldwide. The detection of colon cancer is difficult in early stages. However, the secretory proteins have been used as ideal biomarker for the detection of colon cancer progress in cancer patients. Serum/tissue protein expression could help general practitioners to identify colon cancer at earlier stages. By this way, we use the biomarkers to evaluate the anticancer drugs and their response to therapy in cancer models. Recently, the biomarker discovery is important in cancer biology and disease management. Also, many measurable specific molecular components have been studied in colon cancer therapeutics. The biomolecules are mainly DNA, RNA, metabolites, enzymes, mRNA, aptamers and proteins. Thus, in this review we demonstrate the important protein biomarker in colon cancer development and molecular identification of protein biomarker discovery.