BACKGROUNDMultiple myeloma (MM) is a malignant tumor, which takes the second place in malignant blood disease. The clinical symptoms are complicated that make more difficult to diagnose and therapy. Lots of researches focus on the proteins about MM in order to solve those problems. We used proteomic methods to find potential biomarkers in MM patients.

METHODSWe applied the peptide ligand library beads (PLLBs) to deplete high abundance proteins in serum for finding potential pathogenic factors and biomarkers of MM. Using 1D-Gel-liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 789 and 849 unique serum proteins in MM patients and in healthy controls, respectively.

RESULTSTwenty-two proteins were found differentially expressed between the two groups including serum amyloid A protein, vitamin D-binding protein isoform-1 precursor, plasma kallikrein, and apolipoprotein A-I. Changes of integrin alpha-11 and isoform-1 of multimerin-1 were validated with Western blotting. The linkage of the differentially expressed proteins and the pathogenesis pathways of MM were discussed.

CONCLUSIONSPLLB combined with 1D-gel-LC-MS/MS analysis is an efficient method to identify differentially expressed proteins in serum from patients with MM.

Biomarkers ; blood ; Biomarkers, Tumor ; blood ; Humans ; Multiple Myeloma ; blood ; Peptide Library ; Proteomics ; methods ; Tandem Mass Spectrometry

Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.
Autoantibodies ; blood ; immunology ; Biomarkers, Tumor ; blood ; immunology ; Humans ; Immunotherapy ; Neoplasms ; blood ; therapy ; Tumor Microenvironment

BACKGROUND: We evaluated the performance of Modular Analytics (Roche Diagnostics, Basel, Switzerland) which is combined with automated chemiluminescent immunoassay analyzer and automated chemical analyzer

in order to assess its utility for the improvement of efficiency of routine immuno-chemistry workstation. METHODS: Within- and between-day precision, linearity, and recovery rates were evaluated for 21 items (T3, T4, TSH, E2, LH, Testosterone, FSH, prolactin, AFP, CEA, CA125, CA19-9, total PSA, CRP, ASO, RF, Ig G, Ig M, Ig A, C3C, and C4). Commercialized controls(Roche Diagnostics, Basel, Switzerland) and patient sera for test specimens were used. Centaur(Bayer Diagnostic Division, New York, USA) and LX 2200(Eiken Chemical Co., Tokyo, Japan) were used as the control analyzers to evaluate the correlation. RESULTS: Within-day Coefficients of variation(CVs) was below 5% for all the analytes and between-day CVs was below 5.0% except ASO(8.01%). The linearity was excellent(r2>0.999; slope, 0.98-1.02; p<0.001). Recovery rates for all analytes were in the range of 95% to 103%. The correlation coefficients between modular and Centaur was exceeded 0.971, and between modular

and LX2200 exceeded 0.910, except RF(r=0.834). (P<0.05) CONCLUSION: The recently developed Modular Analytics proved to be highly precise and linear for quantitative analysis of hormones, tumor markers, and serum proteins in routine immuno-chemistry workstation. Correlations with Centaur and LX 2200 were thought to be good.
Blood Proteins ; Humans ; Immunoassay ; Prolactin ; Testosterone ; Biomarkers, Tumor

Preoperative radiotherapy represents the standard treatment for patients with locally advanced rectal cancer. Unfortunately, the response of individual tumors to multimodal treatment is heterogeneous and ranges from complete response to complete resistance. This poses a particular problem for patients with a prior resistant tumors because they may be exposed to irradiation, treatment regimens that are both expensive and at times toxic, without benefit. Accordingly, there is a strong need to establish molecular biomarkers that predict the response. Such biomarkers may guide clinicians in choosing the best possible treatment for each individual patient. It is vital to differentiate the molecular biomarkers to deal with the problem. This review summarized the advances in the biomarkers for response to preoperative radiotherapy for rectal cancer.
Biomarkers, Tumor ; blood ; Combined Modality Therapy ; Humans ; Rectal Neoplasms ; radiotherapy

OBJECTIVETo observe the dynamic levels of serum Golgi protein 73(GP73) in patients prior to and after the onset of liver cancer, and to explore the related factors.

METHODSFrom 2007 to 2012, a periodical screening program was carried out in a group of high risk population with positive Hepatitis B surface antigens (HBsAg) , twice a year. Their serum specimens from every screening time point were kept in Qidong Biobank until liver cancer was diagnosed. Thirty-nine patients with liver cancer were recruited for the study, each of them at least had three times of specimens collected as well as B ultrasound scan (BUS) exam results at onset of disease and within 30 months before diagnosed, amongst 6 time points. In total, there were 162 specimens collected to test GP73 by double-antibody sandwich enzyme-linked immuno-sorbent assay (ELISA). Statistical analyses of time series and differences among groups were performed by stata software 10.

RESULTSThe average value of 39 patient's GP73 at the time point of liver cancer onset was (126.77 ± 73.73) µg/L, while the values at the other five time points prior to the onset were (128.32 ± 81.18) , (129.97 ± 83.62) , (127.38 ± 80.10) , (135.52 ± 97.88) and (138.24 ± 93.58) µg/L, respectively, with no significant difference (F = 0.07, P = 0.997). No obvious changing trends of GP73 were observed among the 39 liver cancer cases at the 6 time points. All 162 samples were divided into two groups: without hepatic cirrhosis (63 samples) and with cirrhosis (99 samples) according to findings of B-ultrasonic wave; whose average GP73 values were separately (97.16 ± 51.39) and (151.20 ± 91.68) µg/L. The difference showed statistical significance (F = 18.22, P < 0.01). Furthermore, if we grouped the samples by the average value of GP73 at 130.19 µg/L, then there were only 1/14 of the subjects without hepatic cirrhosis having higher GP73 values, but 12 of the 25 subjects with hepatic cirrhosis having higher GP73 values. The difference showed statistical significance (P = 0.013). The results of Linear regression model also showed that there was no correlation between GP73 and time series (t = 0.75, P = 0.455), but significant correlation between GP73 and hepatic cirrhosis (t = 4.30, P < 0.01).

CONCLUSIONNo significant changes of the dynamic levels of GP73 could be found among the liver cancer patients within 30 months prior to the onset of disease. GP73 values of the patients with liver cancer may depend on their background of hepatic diseases; and hepatic cirrhosis might be one of the main influencing factors or confounding factors.

Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; Humans ; Liver Neoplasms ; blood ; Membrane Proteins ; blood ; Retrospective Studies

OBJECTIVETo screen tumor biomarkers in the plasma close related with hypopharyngeal carcinoma.

METHODSPooled plasma from 6 patients with hypopharyngeal carcinoma and 6 healthy individuals were collected. After removal of high-abundance plasma proteins, two-dimensional gel electrophoresis (2-DE) was performed to isolate the total proteins, and the protein spots with more than 2-fold differential expressions were detected by 2D analysis software followed by identification by MALDI-TOF/TOF mass spectrometer. Western blotting was performed to validate the expression level of α2-HS-glycoprotein.

RESULTSA total of 11 differentially expressed protein spots were selected, including 5 upregulated proteins and 6 downregulated proteins. MALDI-TOF/TOF identified the upregulated proteins in hypopharyngeal carcinoma patients as alpha-2-HS-glycoprotein and haptoglobin and downregulated ones as Ig kappa chain C region and apolipoprotein A-I. Western blotting demonstrated that α-2-HS- glycoprotein expression level was consistent with that detected by 2-DE.

CONCLUSIONPatients with hypopharyngeal carcinoma show different plasma protein profiles from healthy individuals. These differentially expressed proteins may serve as potential specific tumor biomarkers for hypopharyngeal carcinoma.

Biomarkers, Tumor ; blood ; Blood Proteins ; metabolism ; Humans ; Hypopharyngeal Neoplasms ; blood ; Male ; Middle Aged ; Proteomics ; methods

Colorectal cancer (CRC) is the most common cancer in digestive system, with the highest mortality rate. Its pathogenesis, diagnosis and treatment have been studied extensively. With the deepening of the investigations, more and more studies show that miRNA is closely related with the carcinogenesis, diagnosis and treatment of CRC. The abnormal expression of blood miRNA is expected to become the biomarkers for early diagnosis of CRC and prognostic evaluation, and it may provide a new strategy for clinical treatment.
Biomarkers, Tumor ; blood ; Carcinogenesis ; Colorectal Neoplasms ; blood ; Early Detection of Cancer ; Humans ; MicroRNAs ; blood ; Prognosis

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.
Autoimmune Diseases/blood* ; Biomarkers, Tumor/blood* ; Cardiovascular Diseases/blood* ; Humans ; Liquid Biopsy ; Neoplasms/blood* ; RNA, Circular/blood* ; RNA, Neoplasm/blood*

P53 gene mutations and the abnormal P53 protein can introduce the production to P53 antibody. A large number of studies showed that serum levels of P53 antibody had the correlation with the prognosis of patients with different cancers, the lymph node invasion and metastasis of colorectal cancer, and its recurrence after the curative resection. And it is possible for its application in predicting the early recurrence and metastasis in colorectal cancer after the curative resection.However, there are still a lot of work needed to be done before its use in the clinical settings.
Antibodies ; blood ; Biomarkers, Tumor ; blood ; Colorectal Neoplasms ; blood ; Follow-Up Studies ; Humans ; Lymph Nodes ; Prognosis ; Tumor Suppressor Protein p53 ; immunology

OBJECTIVE: To investigate the relationship between tumor-associated carbohydrate antigen sTn and endometrial carcinoma, and to evaluate the diagnostic value of 2 test methods. METHODS: A total of 200 patients were enrolled, including 100 subjects with endometrial carcinoma, 42 healthy nonpregnant women, 15 pregnant women without complications, and 43 patients with benign gynecologic diseases. The serum sTn-antigen concentrations were determined by 2 test methods (3P9 combined with 4A6, and B72.3 combined with CC49). RESULTS: There was a significant difference in the value and the positive rate of sTn in the serum between the subjects and the contrasts (P<0.05). The sTn level in the pregnant women was high. The sTn level in the serum and its positive rate in endometrial carcinoma became higher with the clinical stage. 3P9 combined with 4A6 was better than B72.3 combined with CC49 in the detection of sTn in the serum as to sensitivity, specificity, positive-prediction, negative-prediction, and accuracy. CONCLUSION The sTn antigen may become a new serological marker for the diagnosis of endometrial carcinoma, but pregnant women should be excluded. 3P9 combined with 4A6 is better than B72.3 combined with CC49 in the detection of sTn in the serum.
Antibodies, Neoplasm ; blood ; Antigens, Tumor-Associated, Carbohydrate ; immunology ; Biomarkers, Tumor ; blood ; Case-Control Studies ; Endometrial Neoplasms ; blood ; diagnosis ; Female ; Humans