RRC ID 71577
著者 Yamakawa K, Koyanagi-Aoi M, Uehara K, Masuda A, Yanagimoto H, Toyama H, Fukumoto T, Kodama Y, Aoi T.
タイトル Increased expression of SPRR1A is associated with a poor prognosis in pancreatic ductal adenocarcinoma.
ジャーナル PLoS One
Abstract OBJECTIVES:Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC.
METHODS:We examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro.
RESULTS:Among the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression.
CONCLUSION:Increased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC.
巻・号 17(5)
ページ e0266620
公開日 2022-1-1
DOI 10.1371/journal.pone.0266620
PII PONE-D-21-35289
PMID 35617311
PMC PMC9135243
MeSH Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism Carcinoma, Pancreatic Ductal* / pathology Carcinoma, Squamous Cell* / genetics Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Pancreatic Neoplasms* / pathology Prognosis
IF 2.74
リソース情報
ヒト・動物細胞 PK-1(RCB1972) PK-8(RCB2700) KLM-1(RCB2138) PANC-1(RCB2095) MIA Paca2(RCB2094)