Markers For Tumor Diagnosis Research Articles

Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers.

Cancer incidence and mortality are increasing globally, leading to its rising status as a leading cause of death. The Go-Ichi-Ni-San (GINS) complex plays a crucial role in DNA replication and the cell cycle. The GINS complex consists of four subunits encoded by the GINS1, GINS2, GINS3, and GINS4 genes. Recent findings have shown that GINS2 expression is upregulated in many diseases, particularly tumors. For example, increased GINS2 expression has been found in cervical cancer, gastric adenocarcinoma, glioma, non-small cell lung cancer, and pancreatic cancer. It correlates with the clinicopathological characteristics of the tumors. In addition, high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration, inhibiting tumor cell apoptosis, and blocking the cell cycle. This review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor development. GINS2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.

Expression of selected microRNAs in pancreatic ductal adenocarcinoma: is there a relation to tumor morphology, progression and patient's outcome?

Pancreatic ductal adenocarcinoma (PDAC) remains a disease with extremely poor prognosis and limited effective available treatment. Differential expression of miRNAs isolated from tumor tissue has been proposed as a marker for tumor diagnosis, progression, and prognosis. Nevertheless, the prognostic value of miRNAs expression in PDACs for patient outcome still remains unclear. Expression of 7 selected miRNAs, isolated from FFPE samples of 54 PDAC patients, was quantified using RT-qPCR. The relationship of miRNA expression levels with tumor histology, clinicopathological characteristics, patient overall survival (OS), and progress-free survival (PFS), was subsequently evaluated. Overexpression of miR-21, miR-155, and miR-210 was observed in PDACs (up to 72.62, 232.36, and 181.38-fold, respectively), in comparison with non-neoplastic tissues. On the other hand, miR-96 and miR-217 were significantly downregulated in PDACs (up to one hundred times). No differences were, however, noticed between cancer and normal tissues for the expression levels of miR-148a and miR-196a. On the other hand, expression levels of all 7 miRNAs failed to demonstrate a significant correlation with parameters of tumor progression, such as tumor stage, grade, nodal involvement, perineural, and vascular invasion. The positive correlation of miR-210 levels was, however, observed with patient age (ρ=0.35). Additionally, miR-148a and miR-217 expressions have shown a positive association with tubular tumor growth pattern (ρ=0.39; ρ=0.28). The negative correlation of miR-148a values was also demonstrated with dissociative growth pattern and nuclear atypia (ρ=-0.30; ρ=-0.27). Finally, no statistically significant correlation could be demonstrated with the expression levels of all 7 tested miRNAs and PDAC patient survival; neither for OS nor for PFS (p>0.05). Our data have confirmed abnormal miRNAs expression in PDACs in comparison with adjacent non-neoplastic tissue. On the other hand, no correlation was discovered between miRNA expression and parameters of tumor progression. We have found a significant association between histologic tumor growth patterns and miRNA expression, making this work the first study, which analyses this aspect of PDAC. Finally, in our group of patients, no relationship of miRNA levels and patient prognosis could be demonstrated. Therefore, further investigation is required to evaluate the predictive and prognostic potential of miRNAs in a clinical setting.

LncRNA MALAT1 negatively regulates MDSCs in patients with lung cancer.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive functions and contribute to the formation of the tumor microenvironment. Long non-coding (Lnc) RNAs are highly important factors associated with tumors and may be used as markers for tumor diagnosis, which is valuable for targeted therapy. LncRNA MALAT1 is expressed in various tissues and plays a critical role in cell proliferation, including tumorigenesis and metastasis. However, the role of MALAT1 in MDSCs is unclear. In this study, we observed an increased proportion of MDSCs and elevated levels of the related molecule arginase-1 (ARG-1) in peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients. The proportion of CD8+ cytotoxic T lymphocyte (CTL) was significantly decreased in PBMCs from lung cancer patients. Moreover, the proportion of CTL cells was negatively correlated with the proportion of MDSCs. Furthermore, MALAT1 levels were decreased in PBMCs from lung cancer patients. The relative expression of MALAT1 was moderate negatively correlated with the proportion of MDSCs. In vitro results indicate that the knockdown of MALAT1 significantly increased the proportion of MDSCs. Our data provide the first evidence that lncRNA MALAT1 negatively regulates MDSCs and is decreased in PBMCs from lung cancer patients.

Syndecan 1: A Useful Marker for Differential Diagnosis in Pseudocarcinomatous Hyperplasia and Squamous Cell Carcinoma

Some proteins have been used as immunohistochemical markers for tumor diagnosis. Such is the case of syndecan-1, one of the four transmembrane heparin sulfate proteoglycans which are mainly present on the cellular surface. Syndecan-1 is the principal syndecan on the epithelial cells of adult tissue, involved in numerous processes such as cellular growth, differentiation, adhesion, and migration among others.

Research advances of survivin in lung cancer

Survivin is a member of inhibitor of apoptosis protein(IAP) family which is highly expressed in a large number of malignancies, has functions of inhibiting apoptosis, enhancing proliferation and promoting angiogenesis. Studies show survivin will be a marker for tumor diagnosis and a target for anti- cancer therapies. Key words: Lung neoplasms; Apoptosis; Prognosis

P5. Evidence of Pdcd 4 as a novel marker for tumor diagnosis and progression in resected colorectal carcinomas

P5. Evidence of Pdcd 4 as a novel marker for tumor diagnosis and progression in resected colorectal carcinomas

Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2A

University of Michigan Ann Arbor, MI 48109 arul@umich.edu Drs. Wang and Chinnaiyan report being listed as inventors on a patent on the findings of this study filed by the University of Michigan. Koziol JA, Zhang JY, Casiano CA, et al. Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res 2003;9:5120-6. McIntosh MW, Pepe MS. Combining several screening tests: optimality of the risk score. Biometrics 2002;58:657-64. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng per milliliter. N Engl J Med 2004;350:2239-46. [Erratum, N Engl J Med 2004;351:1470.] Brass N, Heckel D, Sahin U, Pfreundschuh M, Sybrecht GW, Meese E. Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma. Hum Mol Genet 1997;6:33-9. 1.

Morphometry of nucleoli and expression of nucleolin analyzed by laser scanning cytometry in mitogenically stimulated lymphocytes

Various attributes of nucleoli, including abundance of the nucleolar product (rRNA), correlate with cell-proliferative status and are useful markers for tumor diagnosis and prognosis. However, there is a paucity of methods that can quantitatively probe nucleolus. The aim of the present study was to utilize the morphometric capacity of the laser scanning cytometer (LSC) to analyze nucleoli and measure expression of the nucleolar protein nucleolin (NCL) in individual cells and correlate it with their state of proliferation. Human lymphocytes were mitogenically stimulated, and at different time points their nucleoli were detected immunocytochemically using NCL Ab. The frequency of nucleoli per nucleus, their area, and the level of expression of NCL, separately in the nuclear and nucleolar compartments, were estimated in relation to the G(0) to G(1) transition and the cell cycle progression. During the first 24 h of stimulation, when the cells underwent G(0) to G(1) transition, their RNA content was increased nearly 8-fold, the level of NCL per nucleus also increased 8-fold, the NCL per nucleolus increased 12-fold, nucleolear area increased 3-fold, and NCL/nucleolar area increased nearly 4-fold. During the subsequent 24-48 h of stimulation, when cells were progressing through S, G(2), and M and reentering the next cycle, the number of nucleoli per nucleus was increased and a massive translocation of NCL from nucleoli to nucleoplasm was observed; its overall level per nucleus, however, still remained high, at 6-fold above of that of G(0) cells. While high expression of NCL in the nucleolar compartment correlates with the rate of rRNA accumulation in the cell and is a sensitive marker of the G(0) to G(1) transition, the cells progressing through the remainder of the cycle are better distinguished from G(0) cells by high overall level of NCL within the nucleus. Such an analysis, when applied to tumors, may be helpful in obtaining the quantitative parameters related to the kinetic status of the tumor-cell population and tumor prognosis. The capability of LSC to measure the protein translocation between nucleolus and nucleoplasm can be used to study the function and regulatory mechanisms of other proteins that reside in these compartments.