S100P is a novel marker to identify intraductal papillary mucinous neoplasms
ABSTRACT Intraductal papillary mucinous neoplasms of the pancreas are subclassified based on morphological features, and different immunohistochemical profiles have been identified in association with the subtypes. We previously reported that S100P was an early developmental marker of pancreatic carcinogenesis and that there was higher S100P expression in intraductal papillary mucinous neoplasms than in normal pancreatic ductal epithelium. However, there have been no reports on novel diagnostic markers to distinguish intraductal papillary mucinous neoplasm from nonneoplastic lesions. Surgical specimens of intraductal papillary mucinous neoplasm obtained from 105 patients were investigated using immunohistochemistry. S100P expression was not detected in normal pancreatic ductal epithelium but was detected in all intraductal papillary mucinous neoplasm cells (100%) with diffuse nuclear or nuclear/cytoplasmic staining. MUC5AC was also expressed in most of the intraductal papillary mucinous neoplasms (102/105; 97%). Furthermore, S100P was clearly expressed in the invasive component of intraductal papillary mucinous neoplasms (32/32; 100%), including perineural and lymphatic and minimal invasion. On the other hand, MUC5AC was expressed in only 23 cases of 32 invasive components (P < .01). These data suggest that the S100P antibody may be a useful marker for detecting all types of intraductal papillary mucinous neoplasms.
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ABSTRACT: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a five year survival rate of less than 5%. Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. Though many serum markers have been reported to be elevated in patients with PC, so far, most of these markers have not been implemented into clinical routine due to low sensitivity or specificity. In this study, we have identified genes that are significantly upregulated in PC, through a meta-analysis of large number of microarray datasets. We demonstrate that the biological functions ascribed to these genes are clearly associated with PC and metastasis, and that that these genes exhibit a strong link to pathways involved with inflammation and the immune response. This investigation has yielded new targets for cancer genes, and potential biomarkers for pancreatic cancer. The candidate list of cancer genes includes protein kinase genes, new members of gene families currently associated with PC, as well as genes not previously linked to PC. In this study, we are also able to move towards developing a signature for hypomethylated genes, which could be useful for early detection of PC. We also show that the significantly upregulated 800+ genes in our analysis can serve as an enriched pool for tissue and serum protein biomarkers in pancreatic cancer.PLoS ONE 04/2014; 9(4):e93046. DOI:10.1371/journal.pone.0093046 · 3.53 Impact Factor
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ABSTRACT: The occurrence and development of pancreatic cancer is a complex process convoluted by multi-pathogenies, multi-stages and multi-factors. S100 proteins are members of the S100 family that regulate multiple cellular pathways related to pancreatic cancer progression and metastasis. S100 proteins have a broad range of intracellular and extracellular functions, including the regulation of protein phosphorylation and enzyme activity, calcium homeostasis and the regulation of cytoskeletal components and transcriptional factors. S100 proteins interact with receptor for advanced glycation end-products (RAGE), p53 and p21, which play a role in the degradation of the extracellular matrix (ECM) and metastasis, and also interact with cytoskeletal proteins and the plasma membrane in pancreatic cancer progression and metastasis. S100A11 and S100P are significant tumor markers for pancreatic cancer and unfavorable predictors for the prognosis of patients who have undergone surgical resection. Recently, S100A2 has been suggested to be a negative prognostic biomarker in pancreatic cancer, and the expression of S100A6 may be an independent prognostic impact factor. The expression of S100A4 and S100P is associated with drug resistance, differentiation, metastasis and clinical outcome. This review summarizes the role and significance of the S100 family signaling network and related proteins in pancreatic cancer.International Journal of Molecular Medicine 01/2014; 33(4). DOI:10.3892/ijmm.2014.1633 · 1.88 Impact Factor
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ABSTRACT: S100P is a member of the S100 family of calcium-binding proteins, and it participates in pathophysiological events, such as tumor growth and invasion. Based on the striking similarities between trophoblast cells and tumor cells with regard to proliferative and invasive properties, we raised the question of whether and how S100P expresses in trophoblast cells during development. This study aimed to investigate the expression pattern of S100P in the human placenta during pregnancy development. In this experimental study, we collected 16 first-trimester placental tissues, 10 second-trimester placental tissues, and 12 term placentas. The mRNA expression levels of S100P were detected by reverse-transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR, the protein expression levels were detected by western blot, and the localization of S100P was measured by immunohistochemical staining. The values obtained from PCR and western blot analysis were expressed as the mean ± SD. Levene's test was used to test equal variances, and one-way analysis of variance (ANOVA) was used to evaluate differences between groups. Protein and mRNA expression of S100P could be detected in placenta during pregnancy, with minor higher levels in first-trimester (p>0.05). Immunohistochemical staining revealed that S100P protein was strongly expressed in syncytiotrophoblasts, and moderate expression was detected in villous cytotrophoblasts and cytotrophoblast columns. The S100P protein was localized to both cytoplasm and nuclei in syncytiotrophoblasts, while it only existed in the cytoplasm of cytotrophoblasts. S100P was strongly detected in human placenta during pregnancy. The specific expression and distribution of S100P in human placenta throughout gestation suggested that S100P function might vary with its location in the placenta.International journal of fertility & sterility 02/2015; 8(4):445-52. · 0.47 Impact Factor