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Precision medicine is becoming the goal of translational research on colorectal cancer. Accurate molecular subtyping contributes to better guidance of clinical practice. The current TNM staging system of colorectal cancer is inadequate in terms of guiding clinical practice, such as the underestimation of prognosis of with stage II( and III( colorectal cancer TNM staging, and identification of high-risk and low-risk patients with stage II( colorectal cancer. Researchers from Europe and US have proposed a number of molecular subtypings with clinicopathological phenotypes and molecular phenotypes, which has certain practical significance and is beneficial to the choice of treatment regimen and targeted drugs. But the current results of subtyping research require further validations by clinical large scale multi-center trials. Based on precision medicine, molecular subtyping gradually reveals its clinical significance and is optimized through combining genomics with various clinical phenotypes, indicating its guidance for clinical practice, which is the inevitable course of precision medicine accomplishment. In recent years, there have been many new advances in colorectal cancer liver metastasis treatment. The prognosis of colorectal cancer patients undergoing resection of liver metastasis lesion is similar to those with stage III(. Early recurrence within 6 months after translational treatment and resection occurred in about one third of the patients with initially unresectable liver metastasis, and the overall survival was poor. Thus, an evaluation system should be established in order to avoid the strong therapy and strive for better quality of life in some patients. Individualized treatment for colorectal cancer is emphasized increasingly. Body fluid (peripheral blood and urine) marker detection is a recent research hotspot, including serum protein(polypeptide), plasma miRNA, circulating tumor cells and circulating nucleic acid.
Subject(s)
Humans , Biomarkers, Tumor , Blood , Urine , Colorectal Neoplasms , Diagnosis , Pathology , Therapeutics , Liver Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Precision Medicine , Prognosis , Quality of Life , Translational Research, BiomedicalABSTRACT
Objective To identify the differential inflammation factors in nephroblastoma tissue using proteomics technology and analyze its relationship with clinical stage,pathological phenotype,lymph node metastasis,vascular invasion.Methods From Jan 2010 to Dec 2014,nephroblastoma tumor tissues from 40 patients were obtained.Meanwhile,the 35 tissue near proximal kidney and 25 tissues distal kidney were also obtained.The classification of clinical stage included Ⅰ stage in 6 cases,Ⅱ stage in 12 cases,Ⅲ stage in 13 cases and Ⅳ stage in 9 cases.Other characters contained good prognosis type in 37 case,poor prognosis type in 3 cases,lymphatic metastasis in 17 cases,no sign of lymphatic metastasis in 23 cases,vascular invasion in 9 cases and non-vascular invasion in 31 cases.The SELDI-TOF-MS was used for screening differential protein peaks among three groups.Then,SPE and TRICINE-SDS-PAGE were used to separate and purificate the protein,which showed high peaks expression in tumor tissue,respectively.After in-gel digestion,we received the identification of targeted proteins according to sequence information through Nano-LC-MS/MS.Finally we compared differential expression of inflammatory peaks in different groups of clinical stage,pathological type,lymph node metastasis and vascular invasion.Results All the peaks high expression in tumor tissue,m/z12138 and m/z 13462 are identified as MIF and NAP-2.Expression of two protein peaks in tumor tissue(1437.8 + 997.3,1730.4 + 1147.8) is higher than those in proximal tissue (952.6 + 591.2,1031.1 + 1120.8) and in distal tissue(315.4 + 296.5,114.7 + 118.9),which showed the significant difference (P ＜ 0.001).According to the clinic stage classification,the expression of those protein were 678.8 + 189.0,746.2 + 238.7 in stage Ⅰ,664.0 + 202.0,1180.7 + 404.9 in stage Ⅱ,1524.7+407.9,2160.4 + 1252.3 in stage Ⅲ and 2850.2 + 861.2,2498.4 + 1290.5 in stage Ⅳ.Based on the other characters,expression of those protein were the 1271.7 + 809.2,1553.3 + 991.4 in good prognosis type,3487.2 + 166.2,3915.1 +507.3 in poor prognosis type,2207.1 +961.7,2569.5 + 1285.2 in lymph node metastasis,869.2 + 474.6,1110.2 + 433.6 in non-lymph node metastasis,2850.2 + 861.2,2498.4 +1290.5 in vascular invasion and 1027.8 + 521.3,1507.5 + 1019.9 in non-vascular invasion.All the comparison results have significant statistical difference (P ＜ 0.001).Conclusion MIF and NAP-2significantly increase in nephroblastoma tumor tissue.Meanwhile,there was obvious relationship between those protein with clinical stage,pathological type,lymph node metastasis and vascular invasion.
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Objective To explore the diagnostic model and clinical application value of serum proteomic fingerprint in inflammatory bowel disease (IBD) .Methods Serum proteome profiles of 72 IBD patients (54 Crohn′s disease (CD) and 18 ulcerative colitis (UC) and 44 healthy controls were analyzed by the weak cation exchange (WCX) beads combined matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF‐MS ) technique . Among three groups , every two groups were compared .Wilcoxon rank sum test was used to screen out the peaks of difference expressed protein (P<0 .05) .Genetic algorithm combining with support vector machine (SVM ) was utilized to select the best diagnostic model .The predictive effects of this model was evaluated by leave one out method (LOO ) . Results The 10 most discriminating protein peaks were screened out between CD group and healthy control group , between UC group and healthy control group , between CD group and UC group . A diagnostic model established with four protein peaks ,the mass‐to‐charge ratio (M /Z ) of them was 3 275 .29 ,4 963 .91 ,4 980 .53 and 5 336 .90 ,could better distinguish CD and healthy controls .The specificity was 97 .7% ,and the sensitivity was 92 .6% in CD diagnosis .A diagnostic model established with four protein peaks ,the M /Z of them was 2 272 .41 ,2 660 .42 ,3 029 .77 and 5 002 .78 ,could better distinguish UC and healthy controls .The specificity was 100 .0% ,and the sensitivity was 94 .4% .A specificity was 50 .0% and sensitivity was 88 .9% in CD diagnosis with the diagnostic model of six protein peaks and the M /Z of them was 2 082 .63 ,2 210 .64 ,4 039 .02 ,4 298 .30 ,4 978 .03 ,5 002 .22 .Conclusion The diagnostic model of serum difference expressed protein in CD and UC is established by MALDI‐TOF‐MS technique and genetic algorithm combining with SVM ,which has high diagnostic value in IBD .
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Objective To identify novel biomarkers from urinary protein profiles for the early diagnosis of nephritis in patients with Henoch-Sch(o)nlein purpura by surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS) technique.Methods Urine samples were collected from 60 untreated patients with Henoch-Schonlein purpura,including 30 patients with nephritis and 30 without.SELDI-TOF-MS technique was used to characterize the protein profile in these urine samples,and the Zhejiang University Cancer Institute-Protein Chip Data Analysis System (ZUCI-PDAS) to identify urine protein markers and construct diagnostic model for nephritis in patients with Henoch-Schonlein purpura.Results Totally,154mass peaks were identified with high quality,and two proteins at a mass-to-charge ratio (m/z) of 2454.971 and 2439.686 showed significantly differential expression between the two groups of patients (P ＜ 0.05).Seven biomarkers were used to establish a diagnostic model.As estimated by the leave-one-out cross-validation,the diagnostic model distinguished patients with nephritis from those without with a specificity of 71％ and sensitivity of 84％.Conclusions The developed diagnostic model based on SELDI-TOF-MS technique and bioinformatics is somewhat specific and sensitive for the prediction of nephritis in patients with Henoch-Schonlein purpura.
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AIM: To detect the serum proteomic patterns in patients of breast cancer by the method of SELDI-TOF-MS and CM10 ProteinChip, and to screen the biomarker candidates, build and validate the diagnostic models, and evaluate its clinical value in surveillance and follow-up after operation. METHODS: The SELDI-TOF-MS technology and CM10 ProteinChip were used to detect the proteomic patterns of serum from 63 breast cancer patients and 40 healthy women. The biomarker candidates were screened and the diagnostic models were constructed by ZJU-PDAS software. Meanwhile, the model was blind-validated in another 23 patients and 20 healthy women. At the same time, 16 serum samples were detected to evaluate its value in surveillance and follow-up after operation. RESULTS: The best model was composed by two protein peaks (BC1/3.9 kD and BC2/5.6 kD) with its sensitivity and specificity of 87.30% (55/63) and 95.00% (38/40), respectively. The sensitivity and specificity in the blind-validation of new cases were 95.65% (22/23) and 85.00% (17/20), respectively. The diagnostic efficacies were the same to the patients of different stages (P>0.05). The expression of BC1 increased while BC2 decreased after operation. The expression of BC2 in the patients with recurrence or metastasis was higher than that in the tumor-free survivors (P<0.05). CONCLUSION: This method shows its potential in detection, surveillance and follow-up after operation. The method is also useful for screening the novel and better biomarkers in breast cancer.
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Objective To evaluate the potential differences in serum proteomic profiles between patients with esophageal squamous cell carcinoma(ESCC)and precancerous lesions in order to establish proteomic pattern model for diagnosis of ESCC and precancerous lesions in high risk area,and to investigate its value in screening ESCC.Methods The serum and endoscopic biopsy samples were obtained from 38 normal controls,63 patients with atypical hyperplasia(class Ⅰ 26 cases,class Ⅱ 26 cases,class Ⅲ 11 cases)and 36 patients with advanced esophageal carcinoma.The serum proteomic patterns were examined using surface enhanced laser desorption/ionization time of flight mass spectrometry(SELDI-TOF-MS)and CM10 protein chip.The data was analyzed and disease diagnostic models were established using support vector machine(SVM).The diagnostic model was evaluated and validated by leave one cross validation.Results ①The diagnostic model could differentiate advanced esophageal carcinoma from normal controls with a specificity of 89.47%and a sensitivity of 83.33%.②The results delivered 92.31%,80.77% and 90.91%specificity,and 80.56%,83.33%and 94.44%sensitivity for discrimination of atypical hyperplasia Ⅰ,Ⅱand Ⅲ,respectively,using diagnostic models.③Four(4291,5644,5664,8775)m/z peaks observed repeatedly using diagnostic models.Conclusions The SELDI-TOF-MS and SVM provide a new approach for discrimination of ESCC and precancerous lesions in high risk area.Four(4291,5644,5664,8775)m/z peaks may considered as potential biomarkers which related to the ESCC and esophageal precancerous lesions.
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Objective To characterize mycosis fungoides (MF)-associated serum proteins by surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS) technique. Methods Serum samples were collected following informed consent from 15 patients with MF and 15 patients with chronic eczema or neurodermatitis. Serum protein profiles were detected by CM10 protein chip combined with SELDI-TOF-MS. The proteins differentially expressed between MF and chronic eczema or neuroder matitis were assessed by the Zhejiang University Cancer Institute - ProteinChip Data Analysis System (ZUCIPDAS). Results A total of 329 protein peaks were detected from these patients, significant difference was observed in only 30 protein peaks. The optimal diagnostic model was developed by support vector machine algorithm with two protein peaks at Mass/Charge (m/z) 3939 and 5909 respectively. The expression of protein peak at m/z 3939 was higher in chronic eczema and neurodermatitis than in MF, while that at m/z 5909 appeared to express in an opposite way. In simulation training, this model proved to be able to distinguish MF from chronic eczema and neurodermatitis with both the specifity and sensitivity being 100 percent. The leave-one-out cross-validation also revealed a specificity and sensitivity of 100 percent for this model in the comparison of MF with chronic eczema and neurodermatitis. Conclusion These results suggest that SELDITOF-MS technique combined with bioinformatics is highly specific and sensitive in the diagnosis of MF.
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Objective:To probe e ect of a Chinese compound recipe of nourishing yin and clearing heat and prednisone on nuclear protein of splenic lymphocytes in mice.Methods:MRL/LPR female lupus mice were divided into four groups respectively treated with isotonic Na chloride,traditional Chinese medicine,Western medicine and integrated Chinese and Western medicine,then nucleoproteins of splenic lymphocytes were extracted and detected by SELDI-TOF-MS method.Result:There were some proteins in control group which aggravated autoimmune course,and some proteins in Western medicine group which rivalried immunological activity;integrated Chinese and Western medicine and Western medicine showed similarly e ect on nucleoprotein of splenic lymphocytes.Conclusion:The recipe of nourishing yin and clearing heat and prednisone can treat the disease by uencing in the di erentiation of splenic lymphocytes and the expression of proteins.