The dual-crosslinked prospective values of RAI14 for the diagnosis and chemosurveillance in triple negative breast cancer.

OBJECTIVE: The exploration of non-invasive biomarkers for assessing tumor response is critical to optimize treatment decisions. In this study, we aimed at determining the potential role of RAI14 in the early diagnosis and evaluation of chemotherapy efficacy in triple-negative breast cancer (TNBC). METHODS: We recruited 116 patients newly diagnosed with breast cancer, 30 patients with benign breast disease and 30 healthy controls. In addition, 57 TNBC patients were collected in serum at different time points (C0, C2 and C4) for chemotherapy monitoring. The expression of serum RAI14 and CA15-3 were quantified by Elisa and electrochemiluminescence assay, respectively. Then we compared the performances of markers with the chemotherapy efficacy assessed by imaging. RESULTS: RAI14 is significantly overexpressed in TNBC and is linked to adverse clinicopathological features such as tumor burden, CA15-3 levels and the ER, PR, and HER2 status of the patients. ROC curve analysis showed that RAI14 improves the diagnostic performance for CA15-3(AUCRAI14 = 0.934 vs. AUCCA15-3 = 0.836), especially embodied in early-stage breast cancer diagnosis and patients with CA15-3 negativity. Furthermore, RAI14 behaves well in reproducing treatment response which was consistent with clinical Imaging assessment. CONCLUSIONS: Recent studies showed that RAI14 has a complementary effect to CA15-3 and a test combining the two parameters can improve the detection rate of early triple-negative breast cancer. At the same time, RAI14 plays a more important role in chemotherapy monitoring than CA15-3 as the change in its concentration is in line with the tumor volume variation. Taken together, RAI14 is a reliable novel marker in the early diagnosis and chemotherapy monitoring of triple-negative breast cancer.

High Expression of RAI14 in Triple-Negative Breast Cancer Participates in Immune Recruitment and Implies Poor Prognosis Through Bioinformatics Analyses.

Objective: The purpose of current research is to explore the function of retinoic acid-induced protein 14 (RAI14), being a reciprocal protein of carboxypeptidase N1 (CPN1), and as a biomarker for prognosis and immunoregulatory effects in breast cancers. Methods: Interacting proteins of CPN1 were characterized by co-immunoprecipitation (CO-IP) and mass spectrometry. We evaluated RAI14 expression and related clinical prognosis based on bioinformatics methods. The level of relevance between RAI14 and infiltrating immune cells biomarkers was investigated by using TIMER and certificated by immunohistochemical staining and cytology experiments. Results: RAI14 is an interacting protein of CPN1. Higher RAI14 expression in TNBC was significantly correlated with poor prognosis in TNBC, especially (RFS: HR = 1.32, p = 0.015; DFS: HR = 1.18, p = 0.035). The estrogen receptor (ER), P53 status, and histological types and triple-negative status were observed and correlated with RAI14 expression. Moreover, the level of RAI14 was positive in relation with the expression of CD163 (M2 macrophages marker, r = 0.393, p = 1.89e-06) and PD-1 (T-cell exhaustion marker, r = 0.626, p = 4.82e-03), indicating RAI14 levels were mainly related to M2 macrophages and T-cell exhaustion infiltration in TNBC. Furthermore, CPN1 overexpression was accompanied by RAI14 and PD-L1 upregulation, and a correlation was found among them. Conclusions: RAI14 is a potential downstream molecule of CPN1, which may be a potential prognostic biomarker and identification of an immunosuppressive tumor microenvironment in TNBC.

Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer.

BACKGROUND: The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. METHODS: The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. RESULTS: By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3. CONCLUSIONS: CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.

Hepatitis B Virus X Protein Modulates Chemokine CCL15 Upregulation in Hepatocellular Carcinoma.

BACKGROUND: Hepatitis B virus X protein (HBx) is an indispensable progression factor in Hepatocellular Carcinoma (HCC). CCL15 could be a peculiar proteomic biomarker of HCC with tumorigenesis and tumor invasion. OBJECTIVE: The aim of the study was to explore the relationship between HBx and CCL15 expression in HCC. METHODS: HBV-positive HCC pathological tissue samples and corresponding adjacent non-tumor liver tissues were collected. The expression of HBx and CCL15 was analyzed by immunohistochemistry, real-time Polymerase Chain Reaction (PCR), and western blot analysis in tissues or in vitro. RESULTS: The levels of CCL15 mRNA and protein expression in HCC samples were observably higher than those of adjacent non-tumor liver tissues. The CCL15 was significantly associated with the expression of HBx in HBV-positive HCC samples. The up-regulation of HBx induced CCL15 expression in vitro. The high expression score of CCL15 was significant associated with the poor prognosis of HCC patients. CONCLUSION: The CCL15 expression was observably associated with HBx in HCC patients. The CCL15 may be considered as an indicator in the clinical management of HBV-associated HCC.

Serum Carboxypeptidase N1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer.

BACKGROUND: The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3. METHODS: Seventy samples of breast cancer with lymph node metastasis, seventy-three samples of nonmetastatic breast cancer and twenty-five samples of healthy human serum were collected. Serum CA15-3 concentration was determined by Roche Elecsys, and serum CPN1 concentration was determined by ELISA. RESULTS: In breast cancer patients, serum CPN1 concentration was positively correlated with tumour size, clinical stage and CA15-3 concentration (r = 0.376, P<0.0001). ROC curve analysis showed that the optimal critical concentration of CPN1 for breast cancer diagnosis was 32.8pg/ml. The optimal critical concentration of CPN1 in the diagnosis of metastatic breast cancer was 66.121pg/ml. CPN1 has a greater diagnostic ability for breast cancer (AUCCA15-3=0.702 vs. AUCCPN1=0.886, P<0.0001) and metastatic breast cancer (AUCCA15-3=0.629 vs. AUCCPN1=0.887, P<0.0001) than CA15-3, and the combined detection of CA15-3 and CPN1 can improve the diagnostic efficiency for breast cancer (AUCCA15-3+CPN1=0.916) and for distinguishing between metastatic and non-metastatic breast cancer (AUCCA15-3+CPN1=0.895). CONCLUSION: CPN1 can be used as a new tumour marker to diagnose and evaluate the invasion and metastasis of breast cancer. The combined detection of CPN1 and CA15-3 is more accurate and has a certain value in clinical application.

Hypoxia-Induced TGFBI as a Serum Biomarker for Laboratory Diagnosis and Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: To explore novel biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC), from the perspective of tumor hypoxia. METHODS: We screened 29 differentially expressed and hypoxia-upregulated genes from the Oncomine database. A total of 12 secretory proteins that interact with hypoxia-inducible factor 1 (HIF-1A) were selected by STRING (protein-protein interaction networks). After excluding enzymes and collagens, insulin-like growth factor-binding protein 3 (IGFBP3), glycoprotein NBM (GPNMB), transforming growth factor-ß-induced (TGFBI), and biglycan (BGN) were detected by sandwich enzyme-linked immunosorbent assay (ELISA) in patients with cancer and healthy control individuals. RESULTS: The serum level of TGFBI was significantly elevated in patients with PDAC, compared with healthy controls; the assay could discriminate among cases of PDAC in different clinical stages. The amount of TGFBI was significantly decreased after treatment. The combination of TGFBI and cancer antigen (CA) 19-9 was more accurate than TGFBI or CA 19-9 alone as diagnostic markers. Also, TGFBI might be used as a prognostic marker according to the PROGgeneV2 Pan Cancer Prognostics Database. CONCLUSIONS: Serum TGFBI, combined with CA 19-9, offers higher diagnostic value than other methods for patients with PDAC. Also, TGFBI might be used as a prognostic marker.

Clinical value of ROMA index in diagnosis of ovarian cancer: meta-analysis.

OBJECTIVES: The role of retrospective analysis has evolved greatly in cancer research. We undertook this network meta-analysis to evaluate retrospectively the diagnostic value of ROMA in ovarian cancer. MATERIALS AND METHODS: We systematically retrieved 56 relevant articles published about ROMA index from 2009-2018 and about ovarian cancer from China National Knowledge Infrastructure (CNKI), PubMed and EMBASE. Data were comprehensively analyzed by Rev-Man 5.3 and MetaDisc 12.4 software. RESULTS: Data of 5,954 cases were retrieved from 23 literatures. Among them, 2,117 cases were in the ovarian cancer group and 3,837 cases in the control group. The pooled estimates for the ROMA index were sensitivity: 0.90 (95% CI: 0.88-0.93), specificity: 0.91 (95% CI: 0.89-0.94), positive predictive: 0.90 (95% CI: 0.88-0.95), negative predictive: 0.93 (95% CI: 0.91-0.95), and area under ROC curve: 0.96, compared to 0.71 (95% CI: 0.56-0.82), 0.87 (95% CI: 0.80-0.92), 0.82 (95% CI: 0.78-0.86), 0.92 (95% CI: 0.90-0.94), and 0.88 of HE4, respectively. CONCLUSIONS: This meta-analysis confirms that the risk of ovarian malignancy algorithm can facilitate the diagnosis of ovarian cancer to some extent.

Prediction of Lymph Node Metastases in Gastric Cancer by Serum APE1 Expression.

Aims: To investigate the functional role of serum Human apurinic/apyrimidinic endonuclease 1 (APE1) in prediction of lymph node metastasis in gastric cancer patients. Materials and methods: Serum samples were pre-operational collected from 86 patients with gastric cancer from Tianjin Medical University Cancer Institute and Hospital from March 2016 to August 2016. The serum of APE1 was measured by ELISA development kit and other CA242, CA724, CA199 and CEA levels by electrochemiluminescence assay. Results: The total of 86 patients with gastric cancer was classified into two groups (lymph node positive and negative groups). Using ELISA assay, we found out that the concentration of serum APE1 was higher in lymph node positive group than that of lymph node negative group. The receiver operating characteristic (ROC) curve was performed to analyze, indicating that area under the ROC curve of serum APE1 were better than those of each regular markers (CEA+CA199+CA242+CA724) or combination of these markers. Additionally, the APE1 overexpression was uncovered in tissue of gastric cancer patients with lymph nodes metastases, which is correlation with results of serum APE1. Conclusion: Serum APE1 was identified as a valuable marker for prediction of lymph node metastases in patients with gastric cancer.

Role of Carboxypeptidase N Invasion and Migration in Breast Cancer.

BACKGROUND: Carboxypeptidase N (CPN) is highly expressed in breast cancer and plays an important role in cleaving specific polypeptide fragments within the tumor microenvironment, so here we studied the important role of its invasion and migration in breast cancer. METHODS: MDA-MB-231, MDA-MB-468, and MCF-7 cells were selected for cell culture. We used real-time polymerase chain reaction (PCR) and western blotting to determine CPN gene and protein expression. If CPN was obviously expressed, we designed and synthesized a molecular sequence using an RNA interference approach to remove the CPN and observed its proliferation, migration, and invasion within tumor cells. RESULTS: Real-time PCR and western blotting show the following CPN expression: minimal in MDA-MB-468 cells but obvious in MDA-MB-231 and MCF7 cells. MDA-MB-231 breast cancer cell lines were selected for the control group and CPN was knocked out for the experimental group. Compared to the control group, the experimental group had significantly less migration and invasion. CONCLUSION: CPN may play an important biological function in breast cancer and will provide a new target for the effective diagnosis and treatment of breast cancer.