title: Gene expression profile in the activation of subperitoneal fibroblasts reflects prognosis of patients with colon cancer.
abstract: Tumors can create a heterogenetic tumor microenvironment. We recently identified the pathologically unique cancer microenvironment formed by peritoneal invasion (CMPI), and revealed that subperitoneal fibroblasts (SPFs) within peritoneal tissue play a crucial role in tumor progression through their interaction with cancer cells. Therefore, the genes in SPFs altered by cancer stimulation may include some biologically important factors associated with patient prognosis. In this study, we aimed to identify new biomarkers using genes specifically upregulated in SPFs by cancer-cell-conditioned medium (CCCM) stimulation (SPFs CCCM response genes; SCR genes) in colon cancer (CC). We constructed two frameworks using SCR gene data: a publicly released microarray dataset, and validation cases with freshly frozen CC samples to identify genes related to short recurrence-free survival (RFS). In the first framework, we selected differentially expressed genes between the high and low SCR gene expression groups. In the second framework, genes significantly related to short RFS were selected by univariate analysis using all SCR genes, and multivariate analysis was performed to select robust genes associated with short RFS. We identified CTGF, CALD1, INHBA and TAGLN in the first framework, and PDLIM5, MAGI1, SPTBN1 and TAGLN in the second framework. Among these seven genes, high expression of three genes (CALD1, TAGLN and SPTBN1) showed a poor prognosis in our validation cases. In a public microarray dataset, SCR gene expression was associated with the expression of ECM component, EMT, and M2-macrophage associated genes, which was concordant with the pathological features of CMPI. Thus, we successfully identified new prognostic factors.
authors.affiliation: Division of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.|Department of Surgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yokota
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Division of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishizawa
authors.affiliation: Division of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Division of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Division of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Saito
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D030561:Databases, Nucleic Acid; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D015203:Reproducibility of Results; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics
keywords: colon cancer; elastic lamina invasion; subperitoneal fibroblast; tumor microenvironment