STAT1 as a potential prognosis marker for poor outcomes of early stage colorectal cancer with microsatellite instability Journal Article
| Authors: | Tanaka, A.; Zhou, Y.; Ogawa, M.; Shia, J.; Klimstra, D. S.; Wang, J. Y.; Roehrl, M. H. |
| Article Title: | STAT1 as a potential prognosis marker for poor outcomes of early stage colorectal cancer with microsatellite instability |
| Abstract: | Proteomic analyses indicate that STAT1 protein (signal transducer and activator of transcription 1 or transcription factor ISGF-3 components p91/p84) is upregulated in some colorectal cancers. This study examined 736 colorectal cancer patients for the expression of STAT1 protein in tissue specimens, including 614 early stage patients and 122 advanced stage patients. Tissue microarrays were constructed, and STAT1 expression was examined by immunohistochemistry and scored semi-quantitatively. Among all cases, 9% of cases displayed high levels of cytoplasmic expression of STAT1 and 15% of cases had positive nuclear expression. Based on statistical analyses of a cohort of 559 early stage patients with survival data and no neoadjuvant therapy, we found that high levels of cytoplasmic expression of STAT1 correlated with shorter survival time in early stage colorectal cancer, particularly of the microsatellite instability (MSI) subtype. Additional analysis of a 244-case cohort of colorectal cancers from the Cancer Genome Atlas found that STAT1 gene expression correlated positively with PD-L1 (CD274) and PD-1 (PDCD1) but had no correlation with KRAS or BRAF mutation status. STAT1 expression showed no clear correlation with any of the 4 clinical diagnostic markers of mismatch repair, MLH1, MSH2, MSH6, and PMS2, suggesting its potential as an independent outcome marker for MSI cancers. Our findings suggest that STAT1 may be used as a potential prognostic protein marker for stratifying the outcome risk of early stage MSI colorectal cancer. © 2020 Tanaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; protein expression; aged; major clinical study; advanced cancer; cancer patient; cancer staging; colorectal cancer; stat1 protein; gene expression; cohort analysis; cancer genetics; survival time; statistical analysis; early cancer; quantitative analysis; mismatch repair; microsatellite instability; scoring system; cytoplasm; cell nucleus; tissue microarray; oncogene k ras; protein msh6; b raf kinase; mismatch repair protein pms2; programmed death 1 ligand 1; programmed death 1 receptor; clinical outcome; cancer prognosis; human; male; female; article; mutl protein homolog 1; dna mismatch repair protein msh2 |
| Journal Title: | PLoS ONE |
| Volume: | 15 |
| Issue: | 4 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2020-04-10 |
| Start Page: | e0229252 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0229252 |
| PUBMED: | 32275681 |
| PROVIDER: | scopus |
| PMCID: | PMC7147729 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2020 -- Source: Scopus |
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