• R01 CA203810 NCI NIH HHS
• R01 CA278100 NCI NIH HHS

• FFPE tissue
• SLC8A1
• TMT
• TXNDC17
• colorectal cancer
• quantitative proteomics

• Aged
• Animals
• Female
• Humans
• Male
• Middle Aged
• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Adenoma/pathology
• Adenoma/metabolism
• Biomarkers, Tumor/metabolism
• Cell Line, Tumor
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Gene Expression Regulation, Neoplastic
• Paraffin Embedding
• Proteomics/methods
• Thioredoxins/metabolism
• Sodium-Calcium Exchanger/metabolism

• Biomarkers
• Fungicides
• Proteomics
• RNA-Seq
• Transcriptomics
• Zebrafish Embryo

• Animals
• Zebrafish/metabolism
• Transcriptome
• Fungicides, Industrial/toxicity
• Proteomics
• Gene Expression Profiling
• Perciformes/genetics
• Alanine/analogs & derivatives
• Dioxolanes
• Triazoles

• adenoma
• carcinoma
• colon
• microenvironment
• proteomics
• stroma

• cns cancer
• cell signalling

To date, the cause of inflammatory bowel disease (IBD) remains a mystery. A balance between cell proliferation and apoptosis maintains intestinal tissue homeostasis. Dissociation-induced myosin-actin contraction results in stem cell apoptosis. This study aiming to evaluate the influence of the myosin heavy chain 9 (MYH9) gene single nucleotide polymorphisms (SNPs) on inflammatory bowel disease.

and methods: The study carried on eighty patients with IBD and seventy controls. All participants subjected to history taking, thorough physical examination, colonoscopy and laboratory investigations. Genotyping performed for rs4821480 and rs3752462 by SNP assay real-time PCR methods.

On analyzing rs3752462 CT and TT genotypes were significantly more frequent in IBD patients as compared to controls with 4.6 fold increase in the risk of IBD. While on analyzing rs4821480, The TG and GG genotypes have significant increased distribution among the IBD patients as compared to the controls with 5.3 fold increase in the risk of IBD and higher prevalence of GG genotype in patients with low hemoglobin level and higher BMI.

The rs3752462 T allele and rs4821480 G allele of MYH9 are associated with more susceptibility to IBD.

• IBD
• MYH9
• SNP

• actin cytoskeleton
• invasion
• matrix adhesion
• metastasis
• migration
• motor proteins
• tumor growth
• vesicle trafficking

• R01 CA237304 NCI NIH HHS
• R01 DK108278 NIDDK NIH HHS
• R01 DK126702 NIDDK NIH HHS
• R01 DK108278 and R01 DK126702 A.I.I. U01 CA214300 and R01 CA237304 to EH NIH HHS

• colon cancer
• immune cells
• microenvironment
• prognosis stratification
• tumor stroma

• Mechanism
• Platelet
• Thrombocytopenia
• Thrombosis
• Treatment

Steroidogenic enzymes are crucial in prostate cancer (PCa) progression. 17β-Hydroxysteroid dehydrogenase type 4 (HSD17B4), encoded by HSD17B4, lacks catalytic capacity in androgen metabolism. Now the detailed role and molecular mechanism of PCa development are largely unknown. Here we showed that the expression of HSD17B4 was increased in PCa tissues compared to paired paratumor tissues. HSD17B4 knockdown in PCa cells significantly suppressed its proliferation, migration and invasion, while overexpressing HSD17B4 had opposite effects. Mechanistically, we found that the protein level of HSD17B4 was regulated by its acetylation at lysine 669(K669). Dihydroxytestosterone (DHT) treatment increased HSD17B4 acetylation and then promoted its degradation via chaperone-mediated autophagy (CMA). SIRT3 directly interacted with HSD17B4 to inhibit its acetylation and enhance its stability. In addition, we identified CREBBP as a regulator of the K669 acetylation and degradation of HSD17B4, affecting PC cell proliferation, migration and invasion. Notably, in PCa tissues and paired paratumor tissues, the level of HSD17B4 was negatively correlated with its K669 acetylation. Taken together, this study identified a novel role of HSD17B4 in PCa progression and suggested that HSD17B4 and its upstream regulators may be potential therapeutic targets for PCa intervention.

• 17β-Hydroxysteroid dehydrogenase type 4 (HSD17B4)
• acetylation
• chaperone-mediated autophagy
• prostate cancer
• steroidogenic enzymes

Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment.

YWHAZ (also named 14-3-3ζ) is a central hub protein for many signal transduction pathways and plays a significant role in tumor progression. Accumulating evidences have demonstrated that YWHAZ is frequently up-regulated in multiple types of cancers and acts as an oncogene in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion. Moreover, YWHAZ was reported to be regulated by microRNAs (miRNAs) or long non-coding RNAs and exerted its malignant functions by targeting downstream molecules like protein kinase, apoptosis proteins, and metastasis-related molecules. Additionally, YWHAZ may be a potential biomarker of diagnosis, prognosis and chemoresistance in several cancers. Targeting YWHAZ by siRNA, shRNA or miRNA was reported to have great help in suppressing malignant properties of cancer cells. In this review, we perform literature and bioinformatics analysis to reveal the oncogenic role and molecular mechanism of YWHAZ in cancer, and discuss the potential clinical applications of YWHAZ concerning diagnosis, prognosis, and therapy in malignant tumors.

• YWHAZ
• biomarker
• cancer
• function
• molecular mechanism

• S100A9
• Tenascin-c
• colorectal cancer
• serum biomarker

MYH9 was first discovered due to thrombocytopenia caused by MYH9 mutation-related abnormalities. In recent years, researchers have increasingly found that MYH9 plays an important role in cancer as a cytokine involved in cytoskeletal reorganization, cellular pseudopodia formation, and migration. MYH9 is closely related to the progress and poor prognosis of most solid tumors, and it is now accepted that MYH9 is a suppressor gene and plays an important role on the re-Rho pathway. Recent research has been limited to the study of tissues. However, it would be more direct and informative to be able to use hematology to assess tumor prognosis and changes in MYH9 levels and NMMHC-IIA. This article summarizes recent research on MYH9 and provides a reference for future clinical research.

Laser capture microdissection (LCM) allows the capture of cell types or well-defined structures in tissue. We compared in a semi-quantitative way the proteomes from an equivalent of 8,000 tumor cells from patients with squamous cell cervical cancer (SCC, n = 22) with healthy epithelial and stromal cells obtained from normal cervical tissue (n = 13). Proteins were enzymatically digested into peptides which were measured by high-resolution mass spectrometry and analyzed by “all-or-nothing” analysis, Bonferroni, and Benjamini-Hochberg correction for multiple testing. By comparing LCM cell type preparations, 31 proteins were exclusively found in early stage cervical cancer (n = 11) when compared with healthy epithelium and stroma, based on criteria that address specificity in a restrictive “all-or-nothing” way. By Bonferroni correction for multiple testing, 30 proteins were significantly up-regulated between early stage cervical cancer and healthy control, including six members of the MCM protein family. MCM proteins are involved in DNA repair and expected to be participating in the early stage of cancer. After a less stringent Benjamini-Hochberg correction for multiple testing, we found that the abundances of 319 proteins were significantly different between early stage cervical cancer and healthy controls. Four proteins were confirmed in digests of whole tissue lysates by Parallel Reaction Monitoring (PRM). Ingenuity Pathway Analysis using correction for multiple testing by permutation resulted in two networks that were differentially regulated in early stage cervical cancer compared with healthy tissue. From these networks, we learned that specific tumor mechanisms become effective during the early stage of cervical cancer.

• LCM
• PRM
• biomarker
• cervical cancer
• proteomics

• Muc2
• colon
• dietary fats
• goblet cells
• proteome

• Animals
• Body Weight
• Colon/chemistry
• Colon/immunology
• Cytokines/analysis
• Fish Oils/administration & dosage
• Glycosylation
• Male
• Molecular Chaperones/physiology
• Mucin-2/analysis
• Mucin-2/metabolism
• Rats
• Rats, Sprague-Dawley
• Toll-Like Receptors/analysis

Tumor microenvironment is crucial to tumor development and metastasis. Little is known about the roles of stromal proteins in colorectal carcinogenesis. In this study, we used a combination of laser capture microdissection (LCM), iTRAQ labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to compare stromal proteomes in different stages of colorectal cancer. A total of 1966 proteins were identified, and 222 proteins presenting a significant fold change were quantified in different stages. Differentially expressed proteins (DEPs) were subjected to cluster and pathway analyses. We confirmed the differential expression of Tenascin-C and S100A9 using immunohistochemical analysis, and found that the expression levels of S100A9 and Tenascin-C were correlated with TNM stages and metastasis. In addition, our results showed that Tenascin-C was abundantly secreted by the colon cancer cells with high metastatic potential, and highly expressed in lymph nodes with metastasis. Our studies not only shed light on the mechanism by which stromal proteins contributed to colorectal carcinogenesis, but also identified Tenascin-C as a potential stromal biomarker for colorectal cancer metastasis.

• Tenascin-C
• colorectal carcinoma
• multistage carcinogenesis
• quantitative proteomics
• stromal biomarker

The changes of protein expression that are monitored in proteomic experiments are a type of biological transformation that also involves changes in chemical composition. Accompanying the myriad molecular-level interactions that underlie any proteomic transformation, there is an overall thermodynamic potential that is sensitive to microenvironmental conditions, including local oxidation and hydration potential. Here, up- and down-expressed proteins identified in 71 comparative proteomics studies were analyzed using the average oxidation state of carbon (Z_C) and water demand per residue (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$\end{document}n¯H2O), calculated using elemental abundances and stoichiometric reactions to form proteins from basis species. Experimental lowering of oxygen availability (hypoxia) or water activity (hyperosmotic stress) generally results in decreased Z_C or \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$\end{document}n¯H2O of up-expressed compared to down-expressed proteins. This correspondence of chemical composition with experimental conditions provides evidence for attraction of the proteomes to a low-energy state. An opposite compositional change, toward higher average oxidation or hydration state, is found for proteomic transformations in colorectal and pancreatic cancer, and in two experiments for adipose-derived stem cells. Calculations of chemical affinity were used to estimate the thermodynamic potentials for proteomic transformations as a function of fugacity of O₂ and activity of H₂O, which serve as scales of oxidation and hydration potential. Diagrams summarizing the relative potential for formation of up- and down-expressed proteins have predicted equipotential lines that cluster around particular values of oxygen fugacity and water activity for similar datasets. The changes in chemical composition of proteomes are likely linked with reactions among other cellular molecules. A redox balance calculation indicates that an increase in the lipid to protein ratio in cancer cells by 20% over hypoxic cells would generate a large enough electron sink for oxidation of the cancer proteomes. The datasets and computer code used here are made available in a new R package, canprot.

• Compositional biology
• Redox balance
• Thermodynamic potential

• Biomarkers
• HUPO
• big data
• colorectal cancer
• fecal proteomics
• mass spectrometry
• microbiota
• personalised medicine

Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient’s survival.

We analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohistochemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages.

Out of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed different expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues.

We highlighted three proteins that require further investigations to better characterise their role in early CRC carcinogenesis and their potential as early CRC markers.

The online version of this article (doi:10.1186/s12014-017-9143-3) contains supplementary material, which is available to authorized users.

Colon cancer is one of the most common types of gastrointestinal cancers and the fourth cause of cancer death worldwide. To discover novel diagnostic biomarkers for colon cancer and investigate potential mechanisms of oncogenesis, quantitative proteomic approach using iTRAQ-tagging and 2D-LC-MS/MS was performed to characterize proteins alterations in colon cancer and non-neoplastic colonic mucosa (NNCM) using laser capture microdissection-harvested from the two types of tissues, respectively. As a result, 188 DEPs were identified, and the differential expression of two DEPs (DCN and HSPD1) was further verified by Western blotting and immunohistochemistry. KEGG pathway analysis disclosed that the DEPs were related to signaling pathways associated with cancer; furthermore, DCN and HSPD1 are in the relative central hub position among protein-protein interaction subnetwork of the DEPs. The results not only shed light on the mechanism by the DEPs contributed to colonic carcinogenesis, but also showed that DCN and HSPD1 are novel potential biomarkers for the diagnosis of colon cancer.

• DCN
• HSPD1
• Proteomics analysis
• carcinogenesis.
• colon cancer
• iTRAQ

• Biomarkers
• Cancer stem cells
• Colorectal cancer

Colorectal cancer is one of the most common malignant tumors and the fourth cause of cancer-related mortality. It is not easy to be found at the early stage and therefore has a poor prognosis. Thus, new molecular biomarkers are required to improve early diagnosis and discover new effective therapeutic targets. Advances in proteomic technologies have greatly enhanced our understanding of the pathogenesis of colorectal cancer at the protein level, and improved our ability of early diagnosis and treatment. Proteomic studies of colorectal tissues, serum and cell lines have identified differentially expressed proteins, new potential diagnostic biomarkers and clinical drug targets. This article reviews the advances in proteomic study of colorectal cancer in recent years.

• Colorectal cancer
• Proteomics
• Advance

New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer. Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (Z_C) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$\end{document}n¯H2O) is computed by writing the overall formation reactions of proteins from basis species. Using results reported in proteomic studies of clinical samples, many datasets exhibit higher mean Z_C or \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$\end{document}n¯H2O of proteins in carcinoma or adenoma compared to normal tissue. In contrast, average protein compositions in bacterial genomes often have lower Z_C for bacteria enriched in fecal samples from cancer patients compared to healthy donors. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H₂O and fugacity of O₂ that reflect the compositional differences. The compositional analysis suggests that a systematic change in chemical composition is an essential feature of cancer proteomes, and the thermodynamic descriptions show that the observed proteomic transformations in host tissue could be promoted by relatively high microenvironmental oxidation and hydration states.

• Chemical components
• Colorectal cancer
• Gut microbiome
• Proteomics
• Redox potential
• Thermodynamics
• Water activity

• Centrifugal proteomic reactor
• Colorectal cancer
• Endoscopy
• Label-free proteomics
• Minute amount

AIM: To discover novel biomarkers for early diagnosis, prognosis or treatment of human colorectal cancer.

METHODS: iTRAQ 2D LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in the human colonic epithelial carcinogenic process using laser capture microdissection-purified colonic epithelial cells from normal colon, adenoma, carcinoma in situ and invasive carcinoma tissues.

RESULTS: A total of 326 DEPs were identified, and four DEPs (DMBT1, S100A9, Galectin-10, and S100A8) with progressive alteration in the carcinogenic process were further validated by immunohistochemistry. The DEPs were involved in multiple biological processes including cell cycle, cell adhesion, translation, mRNA processing, and protein synthesis. Some of the DEPs involved in cellular process such as “translation” and “mRNA splicing” were progressively up-regulated, while some DEPs involved in other processes such as “metabolism” and “cell response to stress” was progressively down-regulated. Other proteins with up- or down-regulation at certain stages of carcinogenesis may play various roles at different stages of the colorectal carcinogenic process.

CONCLUSION: These findings give insights into our understanding of the mechanisms of colorectal carcinogenesis and provide clues for further investigation of carcinogenesis and identification of biomarkers.

• Colorectal Cancer
• Proteome
• Biomarker
• Carcinogenesis

• Adenoma/chemistry
• Adenoma/pathology
• Biomarkers, Tumor/analysis
• Calcium-Binding Proteins
• Calgranulin A/analysis
• Calgranulin B/analysis
• Carcinoma/chemistry
• Carcinoma/pathology
• Carcinoma in Situ/chemistry
• Carcinoma in Situ/pathology
• Cell Transformation, Neoplastic/chemistry
• Cell Transformation, Neoplastic/pathology
• Chromatography, Liquid
• Colorectal Neoplasms/chemistry
• Colorectal Neoplasms/pathology
• Computational Biology
• DNA-Binding Proteins
• Early Detection of Cancer/methods
• Galectins/analysis
• Humans
• Immunohistochemistry
• Laser Capture Microdissection
• Predictive Value of Tests
• Proteomics/methods
• Receptors, Cell Surface/analysis
• Tandem Mass Spectrometry
• Tumor Suppressor Proteins

• LCM, Laser capture microdissection
• LC⿿MS/MS, Liquid chromatography tandem mass spectrometry
• Label-free LC⿿MS/
• Laser capture microdissection
• MS

• 2D-PAGE
• autism spectrum disorder
• early diagnosis
• nanoLC-MS/MS