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Hormone receptor status is determined primarily to identify breast cancer patients who may benefit from hormonal therapy. The current clinical practice for the testing using either Allred score or H-score is still based on laborious manual counting and estimation of the amount and intensity of positively stained cancer cells in immunohistochemistry (IHC)-stained slides. This work integrates cell detection and classification workflow for breast carcinoma estrogen receptor (ER)-IHC-stained images and presents an automated evaluation system. The system first detects all cells within the specific regions and classifies them into negatively, weakly, moderately, and strongly stained, followed by Allred scoring for ER status evaluation. The generated Allred score relies heavily on accurate cell detection and classification and is compared against pathologists’ manual estimation. Experiments on 40 whole-slide images show 82.5% agreement on hormonal treatment recommendation, which we believe could be further improved with an advanced learning model and enhancement to address the cases with 0% ER status. This promising system can automate the exhaustive exercise to provide fast and reliable assistance to pathologists and medical personnel. The system has the potential to improve the overall standards of prognostic reporting for cancer patients, benefiting pathologists, patients, and also the public at large.

BackgroundDespite the efficacy of immunotherapy, only a small percentage of patients achieves a long-term benefit in terms of overall survival. The aim of this study was to define an immune profile predicting the response to immune checkpoint inhibitors (ICIs).MethodsPatients with advanced solid tumors, who underwent ICI treatment were enrolled in this prospective study. Blood samples were collected at the baseline. Thirteen soluble immune checkpoints, 3 soluble adhesion molecules, 5 chemokines and 11 cytokines were analyzed. The results were associated with oncological outcomes.ResultsRegardless of tumor type, patients with values of sTIM3, IFNα, IFNγ, IL1β, IL1α, IL12p70, MIP1β, IL13, sCD28, sGITR, sPDL1, IL10 and TNFα below the median had longer overall survival (pConclusionThe combined evaluation of soluble molecules, rather than a single circulating factor, may be more suitable to represent the fitness of the immune system status in each patient and could allow to identify two different prognostic and predictive outcome profiles.

Previous studies have reported that dogs with neoplasms had elevated D-dimer levels. However, few studies have addressed whether D-dimer could be an indicator of tumor burden. The clinical significance of paired analysis of pre- and post-operation of D-dimer levels in dogs has rarely been described. The present study investigated the values of D-dimer levels and their correlated hemostatic alterations in dogs with surgically removable benign and malignant tumors. This study analyzed 30 clinically healthy and 30 tumor-bearing dogs and evaluated the hemostatic functions including D-dimer, thromboelastography G (TEG G), fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time, and platelet count. The median level of pre-treatment D-dimer was 0.8 µg/mL (range: 0.1–6.3 µg/mL), whereas the control dogs exhibited a median value of 0.1 µg/mL (range: 0.1–0.1 µg/mL, p < 0.0001). After tumorectomy, the median levels of D-dimer (p < 0.0001), fibrinogen (p < 0.0001), TEG G value (p < 0.01), and aPTT (p < 0.05) were significantly lower than those of the pre-treatment samples. However, further studies are needed to clarify the values of other hemostatic evaluations. The study revealed the clinical significance of D-dimer and its correlated hemostatic parameters by paired analysis in dogs with tumors. Though more cases are needed for solid confirmation, these values could be potential tumor biomarkers for dogs.

The electrical characteristic of cancer cells is neglected among tumor biomarkers. The development of nanoprobes with opposing charges for monitoring the unique electrophysiological characteristics of cancer cells. Micro-nano size adsorption binding necessitates consideration of the nanoprobe’s specific surface area. On the basis of the electrophysiological characteristics of circulating tumor cells (CTCs), clinical application and performance assessment are determined. To demonstrate that cancer cells have a unique pattern of electrophysiological patterns compared to normal cells, fluorescent nanoprobes with opposing charges were developed and fabricated. Graphene oxide (GO) was used to transform three-dimensional (3D) nanoprobes into two-dimensional (2D) nanoprobes. Compare 2D and 3D electrophysiological magnetic nanoprobes (MNP) in clinical samples and evaluate the adaptability and development of CTCs detection based on cell electrophysiology. Positively charged nanoprobes rapidly bind to negatively charged cancer cells based on electrostatic interactions. Compared to MNPs(+) without GO, the GO/MNPs(+) nanoprobe is more efficient and uses less material to trap cancer cells. CTCs can be distinguished from normal cells that are fully unaffected by nanoprobes by microscopic cytomorphological inspection, enabling the tracking of the number and pathological abnormalities of CTCs in the same patient at various chemotherapy phases to determine the efficacy of treatment. The platform for recognizing CTCs on the basis of electrophysiological characteristics compensates for the absence of epithelial biomarker capture and size difference capture in clinical performance. Under the influence of electrostatic attraction, the binding surface area continues to influence the targeting of cancer cells by nanoprobes. The specific recognition and detection of nanoprobes based on cell electrophysiological patterns has enormous potential in the clinical diagnosis and therapeutic monitoring of cancer.

Sperm-associated antigen 6 (SPAG6) is a newly identified cancer-testis antigen that has been revealed to contribute to the occurrence and development of various types of human cancer, such as ovarian, bladder, breast and lung cancer. However, to the best of our knowledge, the expression levels of SPAG6 in breakpoint cluster region (BCR)/ABL1-negative myeloproliferative neoplasms (MPNs) have not been investigated previously. Using reverse transcription-quantitative PCR and different tissue staining techniques, the present study revealed that SPAG6 was expressed by MPN cells, both at the mRNA and protein levels, and that nucleated erythroid precursors and megakaryocytes expressed the highest levels of SPAG6. In addition, SPAG6, which is known as a microtubule-associated protein, was found to exhibit nucleic, cytoplasmic or both cytoplasmic and nucleic subcellular localization patterns within the same patient or cell type; however, it did not always co-localize with β-tubulin. Furthermore, SPAG6 expression was revealed to be associated with fewer splenomegaly [P=0.015 for polycythemia vera (PV) and essential thrombocythemia (ET); and P=0.012 for primary myelofibrosis (PMF)] and myelofibrosis events (P=0.014 for PV and ET; and P=0.004 for PMF). In patients with PMF, upregulated expression levels of SPAG6 were also found to be associated with lower white blood cell counts (P=0.042) and lactate dehydrogenase levels (P=0.012), and higher hemoglobin levels (P=0.031) and platelet counts (P=0.025). In addition, the receiver operating characteristic curve analysis indicated that SPAG6 may be a potential biomarker for distinguishing MPN cases from healthy individuals. In conclusion, to the best of our knowledge, the present study is the first to report that aberrant SPAG6 expression may affect the disease phenotype and serve as a tumor biomarker in BCR/ABL1-negative MPNs.

Simple Summary Triple negative breast cancer lacks targeted therapies and has poor prognosis; chemotherapy is currently the main treatment modality. Growing evidence has shown that breast cancer stem cells are associated with tumor initiation and metastasis and may play a critical role in chemoresistance. Multiple targets against breast cancer stem cells are now under investigation. Recent advances in the role of breast cancer stem cells in triple negative breast cancer and the identification of cancer stem cell biomarkers have paved the way for the development of new targeted therapies. The discovery of potential molecular signaling pathways targeting breast cancer stem cells to overcome chemoresistance and prevent metastasis will improve the overall survival of patients with triple negative breast cancer. Abstract Triple negative breast cancer (TNBC) remains an aggressive disease due to the lack of targeted therapies and low rate of response to chemotherapy that is currently the main treatment modality for TNBC. Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors and recognized as drivers of tumorigenesis. TNBC tumors are characterized as being enriched for BCSCs. Studies have demonstrated the role of BCSCs as the source of metastatic disease and chemoresistance in TNBC. Multiple targets against BCSCs are now under investigation, with the considerations of either selectively targeting BCSCs or co-targeting BCSCs and non-BCSCs (majority of tumor cells). This review article provides a comprehensive overview of recent advances in the role of BCSCs in TNBC and the identification of cancer stem cell biomarkers, paving the way for the development of new targeted therapies. The review also highlights the resultant discovery of cancer stem cell targets in TNBC and the ongoing clinical trials treating chemoresistant breast cancer. We aim to provide insights into better understanding the mutational landscape of BCSCs and exploring potential molecular signaling pathways targeting BCSCs to overcome chemoresistance and prevent metastasis in TNBC, ultimately to improve the overall survival of patients with this devastating disease.

Dysregulated surface glycoproteins play an important role in tumor cell proliferation and progression. Abnormal glycosylation of these glycoproteins may activate tumor signal transduction and lead to tumor development. The tumor microenvironment alters its molecular composition, some of which regulate protein glycosylation biosynthesis. The glycosylation of saliva proteins in lung cancer patients is different from healthy controls, in which the glycans of cancer patients are highly sialylated and hyperfucosylated. Most studies have shown that O-glycans from cancer are truncated O-glycans, while N-glycans contain fucoses and sialic acids. Because glycosylation analysis is challenging, there are few reports on how glycosylation of saliva proteins is related to the occurrence or progression of lung cancer. In this review, we discussed glycoenzymes involved in protein glycosylation, their changes in tumor microenvironment, potential tumor biomarkers present in body fluids, and abnormal glycosylation of saliva or lung glycoproteins. We further explored the effect of glycosylation changes on tumor signal transduction, and emphasized the role of receptor tyrosine kinases in tumorigenesis and metastasis., Graphical abstract Aberrant glycosylation occurs in tumorigenesis and metastasis. Glycoenzymes are regulated differentially in the tumor microenvironment, leading to shorter O-glycans, hypersialylation, or hyperfucosylation.Image 1, Highlights • Fucosylation and sialylation define the malignancy of lung cancer. • Dysregulated fucosyltransferases can affect fucosylation of saliva glycoproteins. • Receptor tyrosine kinases and oncogenic drivers are related to glycosylation in tumorigenesis and metastasis.

The concentration of circulating heat shock protein 70 (Hsp70) was measured in liquid biopsies of canine tumor patients as a potential biomarker. Compared with rodent tumor models, spontaneously occurring tumors in pet dogs reflect the clinical situation of human patients better, as dogs cohabitate with their owners in the same environment, reach a much older age than rodents, can provide blood samples much more frequently, and receive up-to-date medical care and, similar to humans, their tumors show a high genetic heterogeneity. Due to the species-specific sequence homology of human and canine Hsp70, two human enzyme-linked immunosorbent assay (ELISA) systems (R&D and lipHsp70) were used to measure canine Hsp70 concentrations in serum and plasma. In general, higher Hsp70 concentrations were found in serum compared with plasma samples of dogs, and the lipHsp70 ELISA detected higher peak concentrations of Hsp70 in a broader range than the R&D ELISA. Compared with a tumor-free control group, serum Hsp70 concentrations were higher in tumor-bearing dogs, irrespective of breed, age, body weight, and gender. A sub-classification of the different tumors according to their cytological characteristics revealed significantly elevated Hsp70 serum concentrations in dogs with round cell tumors (p

Objectives To identify the SPINK1 or SPINK1‐based model as a more reliable biomarker for the diagnosis of hepatocellular carcinoma (HCC). Methods Serum samples and related laboratory parameters were collected from 540 subjects (119 healthy donors, 113 patients with chronic hepatitis B, 122 patients with liver cirrhosis, and 186 patients with HCC). SPINK1 was determined by ELISA assay. Differences in each variable were compared by one‐way ANOVA or Kruskal‐Wallis test. ROC (receiver operating characteristic) curve analysis was conducted to compare the diagnostic efficiency of alpha‐fetoprotein (AFP), SPINK1, and a SPINK1‐based combine model constructed by binary Logistic regression. Results In detecting HCC using the other three groups as control, ROC curve analysis revealed that SPINK1 alone reached AUC of 0.899 (0.866–0.933), with the sensitivity of 0.812 of and specificity of 0.953. The combined model increased the AUC to 0.945 (0.926–0.964) with the sensitivity and specificity of 0.860 and 0.910, respectively. For AFP, significantly lower AUC (p, Candidate biomarkers were obtained from differentially expressed genes derived from 3 GEO datasets, following evaluation of the subcellular location; SPINK1, a extracellularly located protein, was selected for validation in clinical samples. The serum concentration of SPINK1 was determined by ELISA assay and compared between HCC and Non‐HCC groups, or HCC subgroups. The variables with significant differences were then included for construction of diagnostic model by binary logistic regression. Performance of each variable alone or in combination was analyzed by ROC curves.

Neuroblastoma (NB) is a neuroectodermal embryonic cancer that originates from primordial neural crest cells, and amongst pediatric cancers with high mortality rates. NB is categorized into high-, intermediate-, and low-risk cases. A significant proportion of high-risk patients who achieve remission have a minimal residual disease (MRD) that causes relapse. Whilst there exists a myriad of advanced treatment options for NB, it is still characterized by a high relapse rate, resulting in a reduced chance of survival. Disialoganglioside (GD2) is a lipo-ganglioside containing a fatty acid derivative of sphingosine that is coupled to a monosaccharide and a sialic acid. Amongst pediatric solid tumors, NB tumor cells are known to express GD2; hence, it represents a unique antigen for subclinical NB MRD detection and analysis with implications in determining a response for treatment. This article discusses NB MRD expression and analytical assays for GD2 detection and quantification as well as computational approaches for GD2 characterization based on high-throughput image processing and genomic data analysis.

Early detection and discovery of new therapeutic targets are urgently needed to improve the breast cancer treatment outcome. Here we conducted an official clinical trial with cross-validation to corroborate human plasma Hsp90α as a novel breast cancer biomarker. Importantly, similar results were noticed in detecting early-stage breast cancer patients. Additionally, levels of plasma Hsp90α in breast cancer patients were gradually elevated as their clinical stages of regional lymph nodes advanced. In orthotopic breast cancer mouse models, administrating with recombinant Hsp90α protein increased both the primary tumor lymphatic vessel density and sentinel lymph node metastasis by 2 and 10 times, respectively. What is more, Hsp90α neutralizing antibody treatment approximately reduced 70% of lymphatic vessel density and 90% of sentinel lymph node metastasis. In the in vitro study, we demonstrated the role of extracellular Hsp90α (eHsp90α) as a pro-lymphangiogenic factor, which significantly enhanced migration and tube formation abilities of lymphatic endothelial cells (LECs). Mechanistically, eHsp90α signaled to the AKT pathway through low-density lipoprotein receptor-related protein 1 (LRP1) to upregulate the expression and secretion of CXCL8 in the lymphangiogenic process. Collectively, this study proves that plasma Hsp90α serves as an auxiliary diagnosis biomarker and eHsp90α as a molecular mediator promoting lymphangiogenesis in breast cancer.

Triple negative breast cancer presents higher mortality and poorer survival rates than other breast cancer (BC) types, due to the proneness to brain metastases formation, which are usually diagnosed at advanced stages. Therefore, the discovery of BC brain metastases (BCBM) biomarkers appears pivotal for a timely intervention. With this work, we aimed to disclose microRNAs (miRNAs) and extracellular vesicles (EVs) in the circulation as biomarkers of BCBM formation. Using a BCBM animal model, we analyzed EVs in plasma by nanoparticle tracking analysis and ascertained their blood-brain barrier (BBB) origin by flow cytometry. We further evaluated circulating miRNAs by RT-qPCR and their brain expression by in situ hybridization. In parallel, a cellular model of BCBM formation, combining triple negative BC cells and BBB endothelial cells, was used to differentiate the origin of biomarkers. Established metastases were associated with an increased content of circulating EVs, particularly of BBB origin. Interestingly, deregulated miRNAs in the circulation were observed prior to BCBM detection, and their brain origin was suggested by matching alterations in brain parenchyma. In vitro studies indicated that miR-194-5p and miR-205-5p are expressed and released by BC cells, endothelial cells and during their interaction. These results highlight miRNAs and EVs as biomarkers of BCBM in early and advanced stages, respectively.

Background MicroRNAs have been reported to participate in tumorigenesis, treatment resistance, and tumor metastasis. Novel microRNAs need to be identified and investigated to guide the clinical prognosis or therapy for breast cancer. Method The copy number variations (CNVs) of MIR3613 from Cancer Genome Atlas (TCGA) or Cancer Cell Line Encyclopedia (CCLE) were analyzed, and its correlation with breast cancer subtypes or prognosis was investigated. The expression level of miR-3613-3p in tumor tissues or serum of breast cancer patients was detected using in situ hybridization and qPCR. Gain-of-function studies were performed to determine the regulatory role of miR-3613-3p on proliferation, apoptosis, and tumor sphere formation of human breast cancer cells MDA-MB-231 or MCF-7. The effects of miR-3613-3p on tumor growth or metastasis in an immunocompromised mouse model of MDA-MB-231-luciferase were explored by intratumor injection of miR-3613-3p analogue. The target genes, interactive lncRNAs, and related signaling pathways of miR-3613-3p were identified by bioinformatic prediction and 3′-UTR assays. Results We found that MIR3613 was frequently deleted in breast cancer genome and its deletion was correlated with the molecular typing, and an unfavorable prognosis in estrogen receptor-positive patients. MiR-3613-3p level was also dramatically lower in tumor tissues or serum of breast cancer patients. Gain-of-function studies revealed that miR-3613-3p could suppress proliferation and sphere formation and promote apoptosis in vitro and impeded tumor growth and metastasis in vivo. Additionally, miR-3613-3p might regulate cell cycle by targeting SMS, PAFAH1B2, or PDK3 to restrain tumor progression. Conclusion Our findings indicate a suppressive role of miR-3613-3p in breast cancer progression, which may provide an innovative marker or treatment for breast cancer patients.

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.

Pancreatic cancer (PaCa) is an insidious and highly metastatic malignancy, with a 5-year survival rate of less than 5%. So far, the pathogenesis and progression mechanisms of PaCa have been poorly characterized. Exosomes correspond to a class of extracellular nanovesicles, produced by a broad range of human somatic and cancerous cells. These particular nanovesicles are mainly composed by proteins, genetic substances and lipids, which mediate signal transduction and material transport. A large number of studies have indicated that exosomes may play decisive roles in the occurrence and metastatic progression of PaCa. This article summarizes the specific functions of exosomes and their underlying molecular mechanisms in mediating the initiation and metastatic capability of PaCa.

Pancreatic ductal adenocarcinoma (PDAC) is becoming increasingly more common. Treatment for PDAC is dependent not only on stage at diagnosis, but complex anatomical relationships. Recently, the therapeutic approach to this disease has shifted from upfront surgery for technically resectable lesions to a neoadjuvant therapy first approach. Selecting an appropriate regimen and determining treatment response is crucial for optimal oncologic outcome, especially since radiographic imaging has proven unreliable in this setting. Tumor biomarkers have the potential to play a key role in treatment planning, treatment monitoring, and surveillance as an adjunct laboratory test. In this review, we will discuss common chemotherapeutic options, mechanisms of resistance, and potential biomarkers for PDAC. The aim of this paper is to present currently available biomarkers for PDAC and to discuss how these markers may be affected by neoadjuvant chemotherapy treatment. Understanding current chemotherapy regiments and mechanism of resistance can help us understand which markers may be most affected and why; therefore, determining to what ability we can use them as a marker for treatment progression, prognosis, or potential relapse.

Background Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells. Methods We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments. Results Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73–66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments. Conclusions The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.

We report on the detection of an angiogenic molecule Vascular Endothelial Growth Factor (VEGF) in different biological matrices by means of a new integrated biosensing platform exploiting the properties of Bloch surface waves. The new platform takes advantage of a tandem configuration, in which both label-free and enhanced fluorescence detection are implemented. Specifically designed one dimensional photonic crystals were deposited directly on disposable and low cost plastic biochips. A direct sandwich immunoassay was used to detect VEGF in buffer, cell culture supernatant and human plasma at low concentration (ng/mL). The platform enabled the detection of VEGF in all three matrices with high resolution, fast turnaround time (30 min) and in close agreement with the results of enzyme linked immunosorbent assays.

// Ke Wang 1 , Yansen Bai 2 , Shi Chen 1 , Jiao Huang 1 , Jing Yuan 2 , Weihong Chen 2 , Ping Yao 3 , Xiaoping Miao 1 , Youjie Wang 4 , Yuan Liang 5 , Xiaomin Zhang 2 , Meian He 2 , Handong Yang 6 , Qingyi Wei 7 , Huan Guo 2 and Sheng Wei 1 1 Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, Hubei, China 2 Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 3 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 4 Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 5 Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 6 Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China 7 Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA Correspondence to: Sheng Wei, email: ws2008cn@gmail.com Keywords: tumor biomarker, single nucleotide polymorphisms, genetic correction, digestive cancer, prediction efficiency Received: July 03, 2017 Accepted: September 24, 2017 Published: December 13, 2017 ABSTRACT Although serum tumor biomarkers alpha-fetoprotein (AFP), carbohydrate antigen 19–9 (CA19–9) and carcinoembryonic antigen (CEA) have been used in digestive cancer risk prediction, the prediction efficiency remains unsatisfactory. The aim of this study was to evaluate whether genetic correction could improve the efficiency of these biomarkers for prediction of digestive cancer risk. We conducted a prospective analysis in 9,808 healthy individuals based on a cohort study in the elderly Chinese population. The genotypes of reported single nucleotide polymorphisms (SNPs) associated with serum AFP, CA19–9 and CEA were used to estimate the genetic corrected levels of these markers. Unconditional logistic regression analysis was performed to evaluate the risk of digestive cancer. The Harrell’s C-statistic was used to evaluate the discriminative ability of the raw levels and genetic corrected levels of biomarkers on digestive cancer risk. Up to October 2013, a total of 172 individuals were newly diagnosed with digestive cancer. With the genetic correction, higher odds ratios (ORs) for digestive cancer risk were found for the genetic corrected levels of tumor biomarkers compared with their raw serum levels (1.57 vs. 1.65 for AFP; 1.19 vs. 1.21 for CA19–9; 1.09 vs. 1.10 for CEA, respectively). The same results were observed in the Harrell’s C-statistic analyses. Genetic correction improved the prediction efficiency of tumor biomarkers on the digestive cancer risk in an elderly Chinese population. Our findings provide evidence for further studies of genetic effects on tumor biomarker to improve the predictive efficiency on cancer risk.

Background To investigate the association between serum carbohydrate antigen 125 (CA125) and the presence as well as severity of diabetes retinopathy (DR) in Chinese adult patients with type 2 diabetes. Methods A hospital-based cross-sectional study was conducted from February 2012 to November 2018. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. Vision-threatening DR (VTDR) was diagnosed if subjects had severe non-proliferative DR (NPDR), proliferative DR (PDR), or clinically significant macular edema (CSME). Multivariate logistic regression models were applied to explore the associations. Results Among the 2696 participants, the overall prevalence of DR was 25.1%, of which the prevalence of mild NPDR, moderate NPDR, and VTDR was 10.8%, 4.5%, and 9.9%, respectively. Serum CA125 level was significantly higher in participants with DR and increased with the severity of DR (P = 0.013). After accounting for age, gender, smoking, drinking, duration of diabetes, anti-diabetic agents use, systolic blood pressure, pulse pressure, weight, hemoglobin A1c and fasting plasma glucose levels, CA125 level was significantly associated with subjects in any-severity DR (odds ratio [OR] 1.006 [95% confidence interval CI: 1.002–1.010], P = 0.006) and VTDR (1.008 [1.003–1.013], P = 0.001). When CA125 was treated as categorized variables, the prevalence of VTDR might increase as improving CA125 quartiles (P value for trend = 0.017). Conclusion In this study, serum CA125 level was associated with the presence and severity of DR in Chinese patients with type 2 diabetes. Further prospective studies should be warranted to validate the feasible role of CA125 as well as other biomarkers.

Previous studies have demonstrated that members of the brain-expressed X-linked (BEX) family participate in a wide range of biological functions in normal and tumor tissues. However, their role and clinical significance in lung adenocarcinoma (LUAD) remains unclear. The present study investigated The Cancer Genome Atlas data and revealed that the BEX family was downregulated in LUAD tissues compared with adjacent non-cancerous tissues. Additionally, analysis of LUAD cohorts from the Oncomine database revealed similar results. Furthermore, the expression of BEX members was significantly decreased in several LUAD cell lines compared with normal lung epithelial cells in vitro. The aforementioned data mining and in vitro results suggested that the BEX family may be involved in the development of LUAD. Furthermore, receiver operating characteristic curve analysis revealed that BEX members exhibited high sensitivity and specificity for the diagnosis of patients with LUAD. The low expression levels of BEX1, BEX4 and BEX5 were associated with certain pathologic features, particularly in advanced LUAD. Survival analysis demonstrated that BEX members, particularly BEX4, were involved in the prognosis of patients with LUAD at early and late clinical stages. The results obtained in the current study suggested that BEX members may serve as potential tumor biomarkers for the diagnosis and prognosis of patients with LUAD.

Objective To analyze the utility of carbohydrate antigen (CA)125 and human epididymis protein 4 (HE4) to detect malignancy in women with ovarian endometriosis, when ovarian cancer is suspected and ultrasonography results are inconclusive. Methods Women who underwent surgery between 2015 and 2019 for ovarian endometriosis or for adnexal masses, with a final diagnosis of ovarian carcinoma (clear cell and endometrioid) were included in this retrospective study. The women were divided into three groups: ovarian endometriosis (OE), ovarian carcinoma without endometriosis (OC), and ovarian carcinoma with endometriosis (OC + E). Adnexal masses were assessed preoperatively by transvaginal ultrasonography according to the International Ovarian Tumor Analysis (IOTA) simple rules, and CA125 and HE4 blood levels were obtained. Results Of 208 women, 45 had malignancy, 16 in the OC + E group and 29 in the OC group. According to transvaginal ultrasonography, 13 were classified as undetermined risk of malignancy: OC group: 3, OE group: 3, and OC + E group: 7. When we compared the tumor biomarkers, significant differences in HE4 but not in CA125 levels were found between the groups. Conclusions When ovarian malignancy is suspected in patients with ovarian endometriosis, HE4 is a more useful tumor biomarker to diagnose OC when ultrasonography results are inconclusive.

Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation reaction of nicotinamide, using S-adenosyl-L-methionine as the methyl donor. Enzyme overexpression has been described in many non-neoplastic diseases, as well as in a wide range of solid malignancies. This review aims to report and discuss evidence available in scientific literature, dealing with NNMT expression and the potential involvement in main urologic neoplasms, namely, renal, bladder and prostate cancers. Data illustrated in the cited studies clearly demonstrated NNMT upregulation (pathological vs. normal tissue) in association with these aforementioned tumors. In addition to this, enzyme levels were also found to correlate with key prognostic parameters and patient survival. Interestingly, NNMT overexpression also emerged in peripheral body fluids, such as blood and urine, thus leading to candidate the enzyme as promising biomarker for the early and non-invasive detection of these cancers. Examined results undoubtedly showed NNMT as having the capacity to promote cell proliferation, migration and invasiveness, as well as its potential participation in fundamental events highlighting cancer progression, metastasis and resistance to chemo- and radiotherapy. In the light of this evidence, it is reasonable to attribute to NNMT a promising role as a potential biomarker for the diagnosis and prognosis of urologic neoplasms, as well as a molecular target for effective anti-cancer treatment.

Background Prostate cancer is the sixth leading cause of cancer-related deaths in Japan. We aimed to elucidate the clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan (BBJ) project. Methods Four thousand, seven hundred and ninety-three patients diagnosed with prostate cancer in the BBJ project were included. Clinical and histopathological data, including causes of death, were analyzed. Relative survival (RS) rates of prostate cancer were calculated. Results Four thousand, one hundred and seventy-one prostate cancer patients with available histological data had adenocarcinoma. The mean age of the patients was 72.5 years. The proportion of patients who were non-smokers, non-drinkers, had a normal body mass index, did not exercise, had a normal prostate-specific antigen level, and had a family history of prostate cancer were 30.7%, 28.0%, 66.6%, 58.1%, 67.6%, and 6.5%, respectively. The proportion of patients with Stage II, III, and IV disease were 24.4%, 7.3%, and 4.4%, respectively. After limiting to patients with a time from the initial diagnosis of prostate cancer to entry into the study cohort of ≤90 days (n = 869), the 5- and 10-year RS rates were 96.3% and 100.5%, respectively, although we were unable to consider management strategies due to a plenty of data missing. Conclusions We provide an overview of patients with prostate cancer in the BBJ project. Our findings, coupled with those from various high throughput “omics” technologies, will contribute to the implementation of prevention interventions and medical management of prostate cancer patients., Highlights • Prostate cancer represents the second leading cause of cancer incidence worldwide. • We aimed to provide an overview of patients with prostate cancer. • Based on prostate cancer histology, 99.3% had adenocarcinoma. • The 5- and 10-year relative survival rates were 96.3% and 100.5%. • Future studies will help develop preventive programs for prostate cancer.

The role of microRNAs (miRs) as possible biomarkers and therapy targets has been extensively investigated in a number of types of cancer. However, the aberrant expression of miRs in laryngeal squamous cell carcinoma (LSCC), particularly during the progression of the disease, is poorly understood. In the present study, the role of miRs as possible novel early pre-diagnostic biomarkers of LSCC was investigated. TaqMan probe stem-loop quantitative polymerase chain reaction was utilized to accurately measure the amount of miR-148a and miR-375 in clinical samples of mild dysplasia, moderate dysplasia, severe dysplasia, cancer in situ, laryngeal cancer and normal epithelial controls. The application of miR-148a and miR-375 as potential predictive biomarkers for early diagnosis of LSCC was analyzed. The results of the present study suggested that miR-148a and miR-375 were significantly upregulated in LSCC tissues, and increased expression of miR-375 was associated with a more aggressive phenotype of LSCC. Additional investigation revealed that miR-148a and miR-375 increased during different dysplasia stages of LSCC carcinogenesis, and high-level expression of miR-148a or miR-375 in patients with laryngeal dysplasia may predict subsequent malignant transformation. miR-148a and miR-375 were significantly upregulated during LSCC carcinogenesis and may serve as possible predictive biomarkers for early diagnosis of LSCC.

Objective: To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix. Materials and Methods: A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25–64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. Results: Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0–163.1), sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5, 95% CI 1.75–6.99) and lower sensitivity (27.8%). Conclusion: The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.

Glioblastoma (GBM) is the most common primary central nervous system tumor and one of the most lethal cancers worldwide, with morbidity of 5.26 per 100,000 population per year. These tumors are often associated with poor prognosis and terrible quality of life. Extracellular vesicles (EVs) are membrane-bound nanoparticles secreted by cells and contain lipid, protein, DNA, mRNA, miRNA and other bioactive substances. EVs perform biological functions by binding or horizontal transfer of bioactive substances to target cell receptors. In recent years, EVs have been considered as possible targets for GBM therapy. A great many types of research demonstrated that EVs played a vital role in the GBM microenvironment, development, progression, angiogenesis, invasion, and even the diagnosis of GBM. Nevertheless, the exact molecular mechanisms and roles of EVs in these processes are unclear. It can provide the basis for GBM treatment in the future that clarifying the regulatory mechanism and related signal pathways of EVs derived from GBM and their clinical value in GBM diagnosis and treatment. In this paper, the research progress and clinical application prospects of GBM-derived EVs are reviewed and discussed.

Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops.

Compared with linear RNA, circular RNAs (circRNAs) form a covalently closed circular continuous loop and are highly conserved, stable and tissue-specific. In recent years, circRNAs received considerable attention in the diagnosis, classification, treatment and prognosis of hematological tumors. circRNAs function as microRNA sponges and competitive endogenous RNAs that play an essential role in the translation, regulation and interaction of proteins. The present review discussed the fundamental properties and functions of circRNAs and the latest advancements in the context of circRNAs in the clinical research of hematological malignancies, namely acute and chronic myeloid leukemia, and chronic lymphocytic leukemia. circRNAs show potential in the diagnosis and prognosis of various diseases and can be used as therapeutic targets and biomarkers for disease.

Purpose Gap junctions are specialized membrane structures that form channels between adjacent cells allowing cell communication. Gap junctions and specifically Connexin 43 (Cx43) are down-regulated in cancer; however, there are contrasting reports on how this effects breast cancer patient survival. This paper is the first large-scale tissue microarray analysis of Cx43 expression in breast cancer patients with an associated clinical long-term follow-up. Methods Using a validated TMA of 1118 primary breast cancers, coupled to a comprehensive database of clinicopathological variables, the expression levels and subcellular localisation of Cx43 was assessed by immunohistochemistry. Its impact in terms of survival, distant metastasis-free survival, and clinicopathological variables was determined. Results Patients whose tumors expressed high levels of Cx43 had significantly better survival (p

Long noncoding RNAs (lncRNA) are reported to be potential cancer biomarkers. This study aims to find new lncRNA biomarker relevant to lung adenocarcinoma. Gene expression profile and clinical data of lung adenocarcinoma and lung squamous cell carcinoma patients were downloaded from the UCSC Xena database. These data were analyzed to identify potential lncRNA prognostic biomarkers, and the candidate lncRNAs were analyzed and verified with association analysis, meta-analysis, survival analysis, gene ontology analysis, gene set enrichment analysis, and other statistical methods. A group of 5 lncRNAs was identified from the 1965 differentially expressed (fold-change >2) genes. Four of these 5 lncRNAs were expressed at a lower level in lung adenocarcinoma tissues and the other one at a higher level (P < .0001). A risk score model was constructed using a linear combination of the expression levels of these lncRNAs. High-risk patients showed poorer overall survival (hazard ratio [HR] = 2.14; 95% confidence interval [CI], 1.67-3.06, P < .0001), disease-free survival (HR = 1.84; 95% CI, 1.26-2.35, P = .0007), and recurrence-free survival (HR = 1.51; 95% CI, 1.02-2.40, P = .04). The 5-fold cross-validation and subsequent meta-analysis further verified that patients in the low-risk group had better survival (95% CI, 0.74-1.79, Z = 4.72, P < .00001). Furthermore, both univariate and multivariate Cox regression analyses revealed that the prognostic value of these 5 lncRNAs was independent of other clinical prognostic factors. Further analysis indicated that these 5 lncRNAs might be associated with tumor metastasis. Taken together, our study suggests new prognostic lncRNA biomarkers for lung adenocarcinoma.

Colorectal cancer (CRC) is the third most common cancer disease. Here we examined Nampt expression in patients with CRC and the effect of Nampt on cell viability in CRC cells. Nampt protein was overexpressed in colorectal adenoma as well as colorectal carcinoma. The immunoreactive staining of Nampt was negative in the adjacent normal colorectal tissue, weak in colorectal adenoma, and strong in colorectal carcinoma, which may represent tumor progression. Further evaluation of clinical data showed that Nampt expression was not correlated with the clinicopathological characteristics of CRC. Additionally, our in vitro studies demonstrated that Nampt promotes CRC cell viability, whereas the Nampt inhibitor FK866 suppressed CRC cell viability, which was in concordance with the previous studies in other cancer cells. Treatment with Nampt-siRNA reduced the Nampt protein expression resulting in the inhibition of the cell viability of HCT116 and Caco2. Thus, the involvement of Nampt in cell growth indicates that Nampt may play an important role in colorectal tumorigenesis. As a consequence, our results suggest that Nampt may be considered as a progression marker of colorectal tumor and a potentially therapeutic target for the treatment of CRC.

Galectin-3 is a member of the galectin family, which are β‑galactoside‑binding lectins with ≥1 evolutionary conserved carbohydrate‑recognition domain. It binds proteins in a carbohydrate‑dependent and ‑independent manner. Galectin‑3 is predominantly located in the cytoplasm; however, it shuttles into the nucleus and is secreted onto the cell surface and into biological fluids including serum and urine. It serves important functions in numerous biological activities including cell growth, apoptosis, pre‑mRNA splicing, differentiation, transformation, angiogenesis, inflammation, fibrosis and host defense. Numerous previous studies have indicated that galectin‑3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer. With emerging evidence to support the function and application of galectin‑3, the current review aims to summarize the latest literature regarding the biomarker characteristics and potential therapeutic application of galectin‑3 in associated diseases.

Identifying metastasis remains a challenge for death control and tailored therapy for nasopharyngeal carcinoma (NPC). Here, we addressed this by designing a nomogram-based Cox proportional regression model through integrating a panel of tumor biomarkers. A total of 147 locally patients with advanced NPC, derived from a randomized phase III clinical trial, were enrolled. We constructed the model by selecting the variables from 31 tumor biomarkers, including 6 pathological signaling pathway molecules and 3 Epstein-Barr virus-related serological variables. Through the least absolute shrinkage and selection operator (LASSO) Cox proportional regression analysis, a nomogram was designed to refine the metastasis risk of each NPC individuals. Using the LASSO Cox regression model, we constructed a 9 biomarkers-based prognostic nomogram: Beclin 1, Aurora-A, Cyclin D1, Ki-67, P27, Bcl-2, MMP-9, 14-3-3σ, and VCA-IgA. The time-dependence receiver operating characteristic analysis at 1, 3, and 5 years showed an appealing prognostic accuracy with the area under the curve of 0.830, 0.827, and 0.817, respectively. In the validation subset, the concordance index of this nomogram reached to 0.64 to identify the individual metastasis pattern. Supporting by this nomogram algorithm, the individual metastasis risk might be refined personally and potentially guiding the treatment decisions and target therapy against the related signaling pathways for patients with locally advanced NPC.

// Bing Chen 1, * , Xiao Zeng 1, * , Yu He 1 , Xixi Wang 1 , Ziwei Liang 1 , Jingjing Liu 1 , Peng Zhang 2 , Hongxia Zhu 1, 3 , Ningzhi Xu 1, 3 , Shufang Liang 1 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China 2 Department of Urinary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, P. R. China 3 Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100034, P. R. China * These authors contributed equaly to this work Correspondence to: Shufang Liang, email: zizi2006@scu.edu.cn Keywords: stanniocalcin 2, colorectal cancer, epithelial-mesenchymal transition, tumor biomarker Received: March 26, 2016 Accepted: September 13, 2016 Published: September 20, 2016 ABSTRACT The STC2 protein involves in carcinogenesis and progression of many cancers. It remains unclear how STC2 regulates the epithelial-mesenchymal transition (EMT) process and colorectal cancer (CRC) development. Here we systematically investigated STC2-activated early occurrence of EMT and CRC cell migration in vitro , clinical associations of STC2 with CRC development and patient survival. The secretion and expression level of STC2 were both greatly increased in EMT cells and CRC cells compared with the normal epithelial NCM460 cells. And the conditioned media from EMT cells stimulated epithelia and colon cancer cells to obtain EMT characteristics. STC2 overexpression promoted CRC cell growth and cell migration in vitro , and STC2 enhanced tumor growth in a mouse CRC-xenograft model. Corresponding to EMT marker expression changes, several critical signaling pathway molecules including pERK, pAKT, PI3K and Ras were remarkably increased either in NCM460 cells transfected with STC2 plasmids or in cells induced with exogenous STC2 protein. However blocking AKT-ERK signaling pathways attenuated STC2-activated EMT process. Furthermore the elevated STC2 expressions were also confirmed in 77 clinical tumor tissues and sera from CRC patients, and the increased STC2 in tumor tissues and sera correlated with tumor pathologic stage and poor survival for CRC patients. In conclusion, STC2 promotes CRC tumorigenesis and EMT progression through activating ERK/MEK and PI3K/AKT signaling pathways. STC2 protein is also a potential tumor biomarker for CRC diagnosis and prognosis.

Cell plasma membrane proteins, playing a crucial role in cell malignant transformation and development, were the main targets of tumor detection and therapy. In this study, CyDye/biotin double-labeling proteomic approach was adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western blotting, and immunohistochemical staining were used to validate the differential expression of a novel identified cell surface marker R-cadherin in gastric cancer cells and tissues. Clinicopathological study and survival analysis were performed to estimate its roles in tumor progression and outcome prediction. Real-time PCR and Western blotting showed that the expression level of R-cadherin in gastric cancer were significantly lower than non-cancerous epithelial cell and tissues. Clinicopathological study indicated that R-cadherin was dominantly expressed on cell surface of normal gastric epithelium, and its expression deletion in gastric cancer tissues was associated with tumor site, differentiation, lymph node metastasis, and pTNM (chi-square test, P

Mathias K Gehrmann,1 Melanie A Kimm,2 Stefan Stangl,1 Thomas E Schmid,1 Peter B Noël,2 Ernst J Rummeny,2 Gabriele Multhoff11Department of Radiation Oncology, 2Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyAbstract: Real-time imaging of small tumors is still one of the challenges in cancer diagnosis, prognosis, and monitoring of clinical outcome. Targeting novel biomarkers that are selectively expressed on a large variety of different tumors but not normal cells has the potential to improve the imaging capacity of existing methods such as computed tomography. Herein, we present a novel technique using cmHsp70.1 monoclonal antibody-conjugated spherical gold nanoparticles for quantification of the targeted uptake of gold nanoparticles into membrane Hsp70-positive tumor cells. Upon binding, cmHsp70.1-conjugated gold nanoparticles but not nanoparticles coupled to an isotype-matched IgG1 antibody or empty nanoparticles are rapidly taken up by highly malignant Hsp70 membrane-positive mouse tumor cells. After 24hours, the cmHsp70.1-conjugated gold nanoparticles are found to be enriched in the perinuclear region. Specificity for membrane Hsp70 was shown by using an Hsp70 knockout tumor cell system. Toxic side effects of the cmHsp70.1-conjugated nanoparticles are not observed at a concentration of 1–10µg/mL. Experiments are ongoing to evaluate whether cmHsp70.1 antibody-conjugated gold nanoparticles are suitable for the detection of membrane-Hsp70-positive tumors in vivo.Keywords: heat shock protein 70, tumor biomarker, theranostics, multimodal CT, multispectral CT, k-edge

Proteinchip profiling is a powerful and innovative proteomic technology for biomarker discovery and diagnostic/prognostic assay development. Based on surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen's proteinchip system offers a single, unified, high-throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell, the study of proteomics provides mankind with a better understanding of disease and life. The remarkable findings in disease biomarkers have shed light to the early diagnosis, monitoring and predicting prognosis of various diseases, especially for cancer. In this article, the development and technology of SELDI-TOF MS are introduced. Some research progress and encouraging research results in oncoproteomics, infectious diseases, neurological diseases and diabetes mellitus using SELDI-TOF MS are also reviewed. The paper is closed by the appraisals on its pros and cons, as well as the future prospective is also expounded.

Iroquois homeobox (IRX), containing transcription factor family of homologous genes and proteins, is widely expressed in both vertebrates and invertebrates embryonic tissue expression profiles. They play a crucial role in the regionalization and patterning of tissues and organs during metazoan development. IRX1, belonging to the IRX gene family, codes for active proteins involved in the development of vertebrate nervous system and plays an important role in the development of various other organs during embryo development. It also plays a critical role in the tumor formation and is identified as both the oncogene or tumor suppressor gene in a variety of tumors. This review summarizes the recent discoveries on the genomic structure of IRX1 and the type classification in different species. More specifically, we focused on explaining the key role of IRX1 in tumorigenesis, and development of tumor and influence in biological processes of metazoans, which we hope will provide a better understanding of the mechanism of IRX1.

Purpose: To assess the relationship between the kinetics of the serum CA15-3 level and the five-year disease-free survival rate of breast cancer patients. Methods: The subjects of this study, 297 women who were diagnosed with breast cancer, were the subset of patients operated on at Kosin University Gospel Hospital from January 2008 to December 2010. We evaluated the change of serum CA15-3 levels during outpatient follow-up period. The changing patterns of serum CA15-3 level were divided into 5 categories; surge without decline, surge with incidental decline, decline without surge, decline with incidental surge, and no change. Clinicopathologic factors were evaluated for each group. Results: The number of patients in surge without decline, surge with incidental decline, decline without surge, decline with incidental surge, and no changes groups were 30 (10.1%), 85 (28.6%), 80 (26.9%), 73 (24.6%), and 29 (9.7%), respectively. The clinicopathologic characteristics were not significantly different among these groups. The log rank test found that 5-year disease-free survival rate according to the kinetics of serum CA15-3 levels were significant (P = 0.004) particularly for the surge without decline group. Conclusion: According to the findings of this study, the surge without incidental decline pattern of serum CA15-3 levels during the follow-up period is associated with poor prognosis. Significant association was found among changing patterns of serum CA15-3 levels and breast cancer recurrence rate.