PMID- 26998092 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220317 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 11 IP - 3 DP - 2016 Mar TI - Analysis of the expression of SDF-1 splicing variants in human colorectal cancer and normal mucosa tissues. PG - 1873-1878 AB - C-X-C motif chemokine ligand 12 (CXCL12), also termed stromal cell-derived factor-1 (SDF-1) is a small protein 8-14 kDa in length that is expressed as six isoforms, consisting of SDF-1alpha, SDF-1beta, SDF-1gamma, SDF-1delta, SDF-1epsilon and SDF-1theta. All six isoforms are encoded by the single CXCL12 gene on chromosome 10. This gene regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. The potential role of the novel CXCL12 splice variants as components of the CXCR4 axis in cancer development is not fully understood. The present study aimed to analyze the expression profile of the various SDF-1 isoforms and SDF-1 polymorphisms, and the association with the clinicopathological features and overall survival of patients with colorectal cancer (CRC). SDF-1 polymorphism analysis was performed using restriction fragment length polymorphism (RFLP) analysis in 73 histologically confirmed human CRC tissue samples at various stages of disease. The expression pattern of the SDF-1 isoforms was analyzed by reverse transcription-polymerase chain reaction in 40 histologically confirmed human CRC tissue samples obtained at various stages of disease, as well as in matched adjacent normal mucosa samples. The presence of the CXCL12 gene polymorphism rs1801157 demonstrated an association with local progression of the primary tumor, as indicated by the T stage. The frequency of the GG genotype was slightly increased in patients with stage 3 and 4 tumors (78.0%) compared with the incidence of the GA/AA genotype (69.5%; P=0.067). The expression of SDF-1beta was associated with the presence of metastases (P=0.0656) and the expression of SDF-1gamma was significantly associated with tumor size (P=0.0423). The present study is the first to analyze the association between the expression profile of the chemokine CXCL12 splice variants in human CRC tissues and their clinical relevance. The present results reveal that the CXCL12 G801A polymorphism is a low-penetrance risk factor for the development of CRC, and was associated with the T stage. All six isoforms of SDF-1 were expressed in CRC tissues. The expression of SDF-1beta was found to be associated with metastases and SDF-1gamma appears to be a possible tumor marker for local tumor progression. FAU - Allami, Risala Hussain AU - Allami RH AD - First Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Graf, Claudine AU - Graf C AD - Third Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Martchenko, Ksenia AU - Martchenko K AD - Department of Internal Medicine, Marienhospital Darmstadt, D-64285 Darmstadt, Germany. FAU - Voss, Beatrice AU - Voss B AD - Third Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Becker, Marc AU - Becker M AD - First Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Berger, Martin R AU - Berger MR AD - Research Group Toxicology and Chemotherapy, German Cancer Research Center, D-69117 Heidelberg, Germany. FAU - Galle, Peter R AU - Galle PR AD - First Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Theobald, Matthias AU - Theobald M AD - Third Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Wehler, Thomas C AU - Wehler TC AD - Third Department of Internal Medicine, Johannes Gutenberg University Hospital of Mainz, D-55130 Mainz, Germany. FAU - Schimanski, Carl C AU - Schimanski CC AD - Department of Internal Medicine, Marienhospital Darmstadt, D-64285 Darmstadt, Germany. LA - eng PT - Journal Article DEP - 20160125 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC4774538 OTO - NOTNLM OT - C-X-C motif chemokine ligand 12 OT - colorectal cancer OT - isoforms OT - stromal cell derived factor 1 splice variants EDAT- 2016/03/22 06:00 MHDA- 2016/03/22 06:01 PMCR- 2016/01/25 CRDT- 2016/03/22 06:00 PHST- 2014/05/28 00:00 [received] PHST- 2015/06/22 00:00 [accepted] PHST- 2016/03/22 06:00 [entrez] PHST- 2016/03/22 06:00 [pubmed] PHST- 2016/03/22 06:01 [medline] PHST- 2016/01/25 00:00 [pmc-release] AID - OL-0-0-4139 [pii] AID - 10.3892/ol.2016.4139 [doi] PST - ppublish SO - Oncol Lett. 2016 Mar;11(3):1873-1878. doi: 10.3892/ol.2016.4139. Epub 2016 Jan 25.