279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry.
Tumor site (alveolus) was also associated with shorter disease-free (though not overall) survival, but the association with p27 was independent of stage and site in multivariate analysis.
Tumors with high Skp2 (>20% positive cells) expression invariably showed reduced or absent p27 and tumors with high p27 (>20% positive cells) expression rarely showed Skp2 positivity.
A high incidence of p27 alterations were observed, with reduced p27 expression measured in 16 of 21 (76%) tumors, followed by p53 alterations observed in 13 of 21 (62%) tumors.
A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro.
A significant influence on the survival of stage III patients was also found for the combinations of p21 and p27 proteins with p21+/p27- imparting the best and p21-/p27+ the worst prognosis (P = 0.04). p27 expression was significantly related to oral cancer specimens (P = 0.04) and to moderate and high tumor grade (P = 0.01). p53 expression was not significantly related to any of the examined clinicopathological characteristics.
Abnormalities identified by immunohistochemistry included p21 immunonegativity (60%, 25%, 93%), which was most frequent in TE-GBM (P = .008), strong nuclear p53 staining (29%, 29%, 41%), strong membranous staining for epidermal growth factor receptor (EGFR) (21%, 63%, 19%), which was most frequent in E-GBM (P = .03), and an increased frequency of p27 immunonegativity in gliosarcomas (15% negative, 85% focal) compared with tumors without sarcoma (38% strongly positive) (P = .009).
All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression. p21 and p27 immunoexpressions were significantly correlated with each other (P < 0.01), and the p21-expressing group had higher p27 expression scores (68% vs 22%). p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension.
Among the regulators of tumor cell proliferation and invasiveness analyzed, the downexpression of Chk2 correlated only with reduced expression of p27 and telomerase.
At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates.
Cancers occurring in the major sites of the gastrointestinal tract (esophagus, stomach, and colorectum) and liver show a similar pattern with regard to p27 protein levels. p27 emerges as a statistically significant predictor of survival and tumor behavior.
CHRT was associated with low proliferating tumours, defined by the Ki67 index (3.58:2.60-4.93), HER2 amplified tumours (4.40:1.93-10.06), low expression of the oncogene cyclin D1 (3.14:2.32-4.23) and high expression of the tumour suppressor gene p27 (3.47:2.40-5.01).
Consistent with the in vitro findings, MYC expression was found to be reduced, while p27 expression was found to be elevated, and BIM expression and cleaved PARP levels were found to be increased in trametinib-treated xenograft tumors.
Decreased tumor cell proliferation was caused, in part, by a profound block in cell cycle progression at the G1/S interface in both LS-174T and HT-29 cells exposed to either DPI or DTI; and the G1 block was produced, for LS-174T cells, by upregulation of p27 and a drug concentration-related decrease in the expression of cyclins D1, A, and E that was partially prevented by exogenous H2O2.
Decreased Cyclin D1 and increased CyclinD1/CDK inhibitors p21 and p27 levels in DPN/letrozole treated tumors were observed, suggesting that the combination treatment may inhibit tumor growth by blocking G1/S phase cell cycle progression.
Ectopic miR‑940 accelerated cervical cancer cell growth, proliferation and cell cycle arrest in vitro as well as tumor formation in vivo. p27 and PTEN were evidenced as direct targets for miR‑940 and inhibition of p27 and PTEN recovered the suppressive function of miR‑940-silenced cell towards to proliferation and tumorigenicity in cervical cancer cells.