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Decreased Expression of the Polarity Regulatory PAR Complex Predicts Poor Prognosis of the Patients with Colorectal Adenocarcinoma.

ABSTRACT: Partitioning defective (Par) proteins regulate cell polarity and differentiation. Par3, Par6?, and protein kinase C? (PKC?), which are PAR complex members, have been shown to be associated with oncogenesis and progression. Herein, we report the expression pattern and clinical relevance of Par3, Par6?, and PKC? in colorectal adenocarcinoma (CRAC). A total of 393 primary CRACs, 41 primary-metastatic CRAC pairs, 41 adenomas with low-grade dysplasia, and 41 nontumor colorectal tissue samples were examined by immunohistochemistry and Western blot assays for Par3, Par6?, and PKC? protein expressions. The association Par3, Par6?, and PKC? expressions and clinicopathologic factors, including patient survival, was evaluated. Primary CRACs and adenomas demonstrated higher levels of Par3, Par6?, and PKC? than in nontumor colorectal epithelia. The expressions of Par3, Par6?, and PKC? were higher in primary CRACs as compared to adenomas or in metastatic CRACs. Among primary CRACs, decreased Par3 expression was found to correlate with a high proliferation rate and poor histologic differentiation, decreased PKC? expression was correlated with pathologic TNM stage (I-II vs III-IV) and lymph node metastasis, and decreased Par6? and PKC? expressions were correlated with shortened overall survivals. In metastatic CRACs, decreased PKC? expression was correlated with a shortened metastasis-free survival. While increased Par3, Par6?, and PKC? expressions were implicated in tumorigenesis, decreased expressions of Par3, Par6?, and PKC? were found to be associated with worse clinicopathologic factors in CRAC. In particular, the results of our study suggest that PKC? down-expression is an independent poor prognostic and metastatic factor for CRAC.

SUBMITTER: Yeo MK

PROVIDER: S-EPMC6002354 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Decreased Expression of the Polarity Regulatory PAR Complex Predicts Poor Prognosis of the Patients with Colorectal Adenocarcinoma.

Yeo Min-Kyung MK Kim Jin-Man JM Suh Kwang-Sun KS Kim Seok-Hyung SH Lee Ok-Jun OJ Kim Kyung-Hee KH

Translational oncology 20171218 1

Partitioning defective (Par) proteins regulate cell polarity and differentiation. Par3, Par6β, and protein kinase Cζ (PKCζ), which are PAR complex members, have been shown to be associated with oncogenesis and progression. Herein, we report the expression pattern and clinical relevance of Par3, Par6β, and PKCζ in colorectal adenocarcinoma (CRAC). A total of 393 primary CRACs, 41 primary-metastatic CRAC pairs, 41 adenomas with low-grade dysplasia, and 41 nontumor colorectal tissue samples were ex ...[more]

PMID: 29220829

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Project description:BackgroundInterleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD).MethodsIn this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).ResultsThrough the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients.ConclusionsIn summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.

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Decreased Expression of the Polarity Regulatory PAR Complex Predicts Poor Prognosis of the Patients with Colorectal Adenocarcinoma.

Publications

Decreased Expression of the Polarity Regulatory PAR Complex Predicts Poor Prognosis of the Patients with Colorectal Adenocarcinoma.

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