OBJECTIVE: To detect the serum level of chemokine CXC motif chemokine 10 (CXCL-10) and Krebs von den lungen-6 (KL-6) in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD), and to analyze their correlation with RA-ILD, as well as the significance in RA-ILD. METHODS: A total of 169 RA patients were enrolled in the study. According to imaging findings of with and without ILD in high-resolution computed tomography scans of chest, the subjects were divided into RA-ILD group and RA-non-ILD group. According to the inclusion and exclusion criteria, 80 patients in each of the two groups were finally selected. Two groups were matched according to the 1 ∶ 1 ratio using propensity score matching (PSM). The serum CXCL-10 and KL-6 levels were detected by enzyme-linked immunosorbent assay. The clinical features, laboratory data and medications between the two groups were compared after PSM and the correlation between serum levels and clinical parameters were analyzed. Binary Logistic regression was used to analyze the risk factors of ILD in the RA patients, and the predictive value of CXCL-10 and KL-6 in RA-ILD was evaluated. RESULTS: In this study, 49 patients with RA-ILD and 49 patients with RA-non-ILD were selected by PSM. The levels of CXCL-10 and KL-6 in the RA-ILD group [64.36 (34.01, 110.18) ng/L, 360.70 (236.35, 715.05) U/mL] were significantly higher than those in the RA-non-ILD group [29.80 (16.89, 40.55) ng/L, 210.69 (159.98, 255.50) U/mL] (all P < 0.001). The results of correlation analysis showed that the level of serum CXCL-10 was positively correlated with the Warrick score on chest CT (r=0.378, P=0.007) and negatively correlated with the percentage of forced vital capacity to the predicted value (FVC%, r=-0.338, P=0.018). And the level of KL-6 was positively correlated with rheumatoid factor (RF, r=0.296, P=0.039) and negatively correlated with FVC% (r=-0.436, P=0.002) and the percentage of diffusion capacity for carbon monoxide to the predicted value (DLCO%, r=-0.426, P=0.002). Both univariate and multivariate Logistic regression analysis showed that CXCL-10 and KL-6 were positively correlated with ILD, the values of OR were 1.035 and 1.023 in CXCL-10 and those were 1.004 and 1.005 in KL-6 respectively (P < 0.05). The ROC curves were plotted with CXCL-10 and KL-6. The area under the curve (AUC) was 0.770 and 0.752 respectively. The AUC of combined detection increased to 0.800. CONCLUSION Serum levels of CXCL-10 and KL-6 are significantly elevated in patients with RA-ILD and correlated with the severity of ILD. The combined estimate of them helps to improve the effectiveness of diagnosis.
Humans ; Lung Diseases, Interstitial/etiology* ; Arthritis, Rheumatoid/complications* ; Chemokine CXCL10/blood* ; Mucin-1/blood* ; Female ; Male ; Tomography, X-Ray Computed ; Risk Factors ; Middle Aged

Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report a case of asymptomatic gastric PAMT that was pathologically confirmed after surgical resection. The tumor had a multinodular plexiform growth pattern, bland-looking spindle cells, and an Alcian blue-positive myxoid stromal matrix rich in small blood vessels. Immunohistochemistry analysis revealed that the tumor cells of the PAMT were positive for smooth muscle actin (SMA) and negative for c-kit, CD34, S-100 protein, epithelial membrane antigen (EMA), and desmin. PAMT should be differentiated from other submucosal tumors of the stomach by immunohistochemical findings. Considering the benign features of this tumor, observation without resection may be an option for the treatment of PAMT if the tumor is asymptomatic.
Actins ; Blood Vessels ; Desmin ; Gastrointestinal Tract ; Immunohistochemistry ; Mucin-1 ; Muscle, Smooth ; Myofibroblasts* ; S100 Proteins ; Stomach*

BACKGROUND: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. METHODS: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). CONCLUSIONS: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.
Adult ; Aged ; Area Under Curve ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*diagnosis/genetics/pathology ; Case-Control Studies ; Female ; Humans ; Macrophage Colony-Stimulating Factor/*blood ; Matrix Metalloproteinase 9/*blood ; Middle Aged ; Mucin-1/blood ; Neoplasm Staging ; Poland ; ROC Curve ; Sensitivity and Specificity ; Tissue Inhibitor of Metalloproteinase-1/*blood

PURPOSE: We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis. MATERIALS AND METHODS: Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1. RESULTS: The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients. CONCLUSION: This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC.
Antibodies ; Biomarkers ; Blood Cells ; Carcinoma, Hepatocellular ; Cell Line ; Cholangiocarcinoma ; Epithelial Cells ; Erythrocytes ; Glypicans ; Humans ; Immunohistochemistry ; Keratins ; Liver Neoplasms* ; Liver* ; Methods* ; Mucin-1 ; Neoplastic Cells, Circulating* ; Portal Vein ; Tissue Donors

OBJECTIVETo investigate the expression of long non-coding RNA HOTAIR in the plasma of breast cancer patients and its value in the diagnosis of breast cancer.

METHODSHOTAIR levels were measured in 24 tumor tissues and 70 plasma samples from breast cancer patients using quantitative real-time PCR. The correlations of plasma HOTAIR level with the clinicopathological features of the patients were analyzed. A multivariate logistic regression model was established to analyze the value of plasma HOTAIR in comparison with plasma CA153 and CEA levels for breast cancer diagnosis. We further detected HOTAIR levels in the plasma and breast cancer tissues of 24 patients before and after operation and investigated their correlation.

RESULTSBreast cancer patients had increased expressions of HOTAIR in the tumor tissues and plasma, and plasma HOTAIR level was significantly correlated with estrogen receptor (ER) level (P=0.004) and lymph node metastasis (P=0.010). Receiver operating characteristic (ROC) curve and the multivariable logistic regression model showed that the area under ROC curve (AUC) of plasma HOTAIR was 0.82 (P<0.001) for breast cancer diagnosis with a diagnostic sensitivity and a specificity of 73.3% and 93.3%, respectively. The diagnostic power and specificity of plasma HOTAIR was much higher than those of CA153 (AUC=0.66, P=0.030) and CEA (AUC=0.52, P=0.001), and the combination of the 3 markers further enhanced the diagnostic power (AUC=0.84) and specificity (96.7%). Plasma HOTAIR level was significantly reduced in the patients after the operation (P<0.0001) and showed a moderate correlation with its expression in tumor tissues (r=0.62, P<0.0001).

CONCLUSIONPlasma HOTAIR may serve as a potential biomarker for breast cancer diagnosis.

Biomarkers, Tumor ; blood ; Breast Neoplasms ; blood ; diagnosis ; Carcinoembryonic Antigen ; blood ; Female ; Humans ; Logistic Models ; Lymphatic Metastasis ; Mucin-1 ; blood ; Prognosis ; RNA, Long Noncoding ; blood ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Receptors, Estrogen ; metabolism ; Sensitivity and Specificity

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; blood ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; Female ; Humans ; Male ; Middle Aged ; Mucin-1 ; blood ; Neoplasms ; blood ; complications ; diagnosis ; Prostate-Specific Antigen ; blood ; Retrospective Studies ; Sensitivity and Specificity ; Serpins ; blood ; Venous Thrombosis ; blood ; complications ; Young Adult ; alpha-Fetoproteins ; metabolism

OBJECTIVETo study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).

METHODSelf-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP.

RESULTThe contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05).

CONCLUSIONThere were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.

Adolescent ; Biomarkers ; blood ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lung ; metabolism ; pathology ; Male ; Mucin-1 ; blood ; metabolism ; Pneumonia, Mycoplasma ; blood ; metabolism ; Pulmonary Surfactant-Associated Protein A ; blood ; metabolism ; Pulmonary Surfactant-Associated Protein D ; blood ; metabolism ; Severity of Illness Index

Chemotherapy plays an important role in the treatment of metastatic breast cancer. It is important to monitor chemotherapeutic efficacy, to find a simple and efficient tool to guide treatment, and to predict the efficacy of treatment in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1)-positive circulating tumor cells and MUC1 protein in the peripheral blood of patients with metastatic breast cancer and to investigate their relationship to chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34 patients with newly diagnosed metastatic breast cancer by reverse transcription-polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before chemotherapy and 70.6% after chemotherapy, without a significant difference (P=0.564); MUC1 mRNA expression before chemotherapy had no correlation with treatment effectiveness (P=0.281). The response rate of MUC1 mRNA-negative patients after first-cycle chemotherapy was significantly higher (P=0.009) and the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA-positive patients (P=0.095). MUC1 protein in peripheral blood plasma was detected by an ELISA competitive inhibition assay. The patients with decreased MUC1 protein after chemotherapy had a significantly longer PFS than those with elevated MUC1 protein (P=0.044). These results indicate that the outcomes of MUC1 mRNA-negative patients after chemotherapy are better than those of MUC1 mRNA-positive patients. In addition, patients with decreased expression of MUC1 protein have a better PFS.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Middle Aged ; Mucin-1 ; blood ; genetics ; metabolism ; Neoplastic Cells, Circulating ; metabolism ; RNA, Messenger ; metabolism ; Receptors, Progesterone ; metabolism ; Taxoids ; administration & dosage ; Thiotepa ; administration & dosage

OBJECTIVETo investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer.

METHODSA total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis.

RESULTSFirst, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival.

CONCLUSIONSHigher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

Adult ; Age Factors ; Aged ; Breast Neoplasms ; blood ; pathology ; Carcinoembryonic Antigen ; blood ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mucin-1 ; blood ; Peptides ; blood ; Preoperative Period ; Prognosis ; Receptors, Estrogen ; blood ; Retrospective Studies ; Survival Rate ; Tumor Burden ; Young Adult

OBJECTIVETo analyze the characteristics of serum proteins mass spectra in healthy controls, benign breast tumors, and CA15-3 negative or CA15-3 positive breast cancer patients by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS).

METHODSTissue samples of 113 cases of breast cancer (93 case of CA15-3 negative, 20 case of CA15-3 positive), 103 cases of benign breast tumor and 92 cases of healthy controls were examined and analyzed by SELDI and protein chip (CM10) techniques. Biomarker Pattern Software (BPS) was used to detect the protein peaks significantly different between them and establish a diagnostic pattern which was further evaluated by a blind test.

RESULTSTwelve significantly different protein peaks were found in serum samples between breast cancer patients and healthy controls. Eleven significantly different peaks were found between benign breast tumor patients and healthy controls. By combined analysis of those three different protein mass spectra, the peak 15 952 was found to be significantly different between breast cancer group and healthy controls, and the peak 7985 was significantly different among breast cancer group, benign breast tumor group and health controls. The blind test with the differential proteins for the serum samples of 93 cases of CA15-3 negative breast cancer and 36 cases of benign breast tumors showed that the sensitivity was 80.6% and specificity was 91.7%. The blind test in 20 cases of CA15-3 positive breast cancer and 36 cases of benign breast tumors showed that the sensitivity was 75.0% and specificity was 91.7%. Four significantly different protein peaks were found between the benign breast tumor patients and CA15-3 negative breast cancer patients. No significantly different protein were found between CA15-3 negative and CA15-3 positive patients.

CONCLUSIONSignificantly different protein peaks can be screened out in breast cancer, benign breast tumor patients and healthy controls by SELDI-TOF-MS analysis.

Adenoma ; blood ; diagnosis ; metabolism ; Adult ; Aged ; Biomarkers, Tumor ; blood ; Blood Proteins ; metabolism ; Breast Neoplasms ; blood ; diagnosis ; metabolism ; Carcinoma, Ductal, Breast ; blood ; diagnosis ; metabolism ; Case-Control Studies ; Female ; Fibroadenoma ; blood ; diagnosis ; metabolism ; Humans ; Middle Aged ; Mucin-1 ; metabolism ; Protein Array Analysis ; Proteomics ; methods ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization