title: S100P, a calcium-binding protein, is preferentially associated with the growth of polypoid tumors in colorectal cancer.
abstract: Colorectal cancer (CRC) is a genetically heterogeneous disease with distinct morphological patterns. It has been shown that polypoid and ulcerative CRC displays different genetic alterations. In the present study, we aimed to investigate genes with differential expression patterns between ulcerative and polypoid CRC. cDNA microarray analysis was performed to compare the gene expression profiles in samples of ulcerative and polypoid CRC with paired normal mucosa samples. Potential candidate genes were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemistry. The epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray analysis identified 11 upregulated and 14 downregulated genes which were differentially expressed in samples from both tumor types compared to the matched normal mucosa samples. Among these, S100P was the only upregulated gene preferentially associated with polypoid CRC (P=0.032). The samples of polypoid CRC displayed significantly higher S100P protein and mRNA expression levels than the samples of ulcerative CRC (P<0.05, respectively). Using semi-quantitative immunohistochemical analyses, S100P overexpression was found to be preferentially associated with polypoid CRC (24/30 vs. 14/40, P<0.001). The relative methylation level determined by MSP did not differ significantly between the samples of polypoid and ulcerative CRC (43.36 vs. 49.10%, P=0.168), indicating that promoter hypomethylation was not directly related to the upregulation of S100P mRNA. Our results demonstrate that the upregulation of S100P mRNA and protein expression is a predominant characteristic in polypoid CRC, whereas ulcerative CRC presents with a wide range of expression levels, indicating that S100P overexpression is not a key determinant in conferring invasion properties. The clinicopathological significance of S100P in CRC requires further investigation in well-controlled studies.
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Jy-Ming
authors.initials: JM
authors.lastname: Chiang
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Reping
authors.initials: R
authors.lastname: Tan
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Jen-Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Jinn-Shium
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Pao-Shiu
authors.initials: PS
authors.lastname: Hsieh
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Chung Rong
authors.initials: CR
authors.lastname: Changchien
authors.affiliation: College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Jim-Ray
authors.initials: JR
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D059467:Transcriptome; D047368:Tumor Burden
chemical_list: D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human