Expression of Cell Cycle Regulators P21 and P27 as Predictors of Disease Outcome in Colorectal Carcinoma

Al-Maghrabi, Jaudah; Al-Ahwal, Mahmoud; Buhmeida, Abdelbaset; Syrjänen, Karí; Sibyani, Abdulrahman; Emam, Eman; Ghanim, Ayman; Al-Qahtani, Mohmmad

doi:10.1007/s12029-011-9292-y

Cited by 26 publications

(18 citation statements)

References 35 publications

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“…It is known that p27 expression is lower in a series of human cancers, including CRC and breast and lung cancer (20,31,32). In the present study, 32.79% of tumors showed lower or depleted p27 expression, in agreement with the report of Al-Maghrabi et al (18). The present study found that there were no significant correlations between the loss of p27 expression and gender, age and depth of invasion.…”

Section: Discussionsupporting

confidence: 93%

“…This observation is in agreement with the study by Shapira et al (33), who reported low p27 levels associated with poorly-differentiated tumors, but not with age, gender and clinical stage in CRC. However, Al-Maghrabi et al (18) showed that p27 expression was only associated with depth of invasion and not with tumor grade, lymph metastasis and clinical stage in CRC. Although p27 may be significantly associated with tumor invasiveness characteristics, including grade, depth of invasion and clinical stage, the prognostic value of p27 remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Although p27 may be significantly associated with tumor invasiveness characteristics, including grade, depth of invasion and clinical stage, the prognostic value of p27 remains controversial. Al-Maghrabi et al (18) reported that colorectal tumors with increased p27 expression showed a higher recurrence rate and shorter disease-free patient survival time than those with lower level or completely depleted p27 expression. However, in the present study, it was observed that patients with p27 expression had longer survival times than those with no p27 expression, which was consistent with the study by Bertagnolli et al (26), which described that loss of p27 as associated with reduced survival in colon cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study (17) showed that the decreased expression of p27 was associated with a poor prognosis in CRC. Al-Maghrabi et al (18) showed that p27 positive expression was associated with a high recurrence rate, in conflict with the findings by Zlobec et al (19). …”

Section: Introductionmentioning

confidence: 88%

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Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post-operative stage II and III colorectal cancer

Liang

et al. 2014

Oncology Letters

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Prognostic markers for colorectal cancer (CRC) have not yet been fully investigated. Phosphatase and tensin homolog (PTEN), p27 and Cyclin D1 play significant roles in tumorigenesis and cell cycle regulation, and therefore require evaluation for their prognostic value in this disease. The aim of the present study was to assess the prognostic value of the single and combined expression of PTEN, p27 and Cyclin D1 in CRC patients. Protein expression levels of PTEN, p27 and Cyclin D1 were examined by immunohistochemistry from 61 patients with CRC in either stage II or III. In the CRC tissues, the frequencies of PTEN(−), p27(−) and Cyclin D1(+) expression were 42.62% (26/61), 32.79% (20/61) and 45.90% (28/61), respectively. Depletion of PTEN and p27 was more common with respect to stage III, low grade and lymph node metastasis compared with stage II, moderate grade and no lymph node metastasis (P<0.05). Cyclin D1-positive expression was frequently detected in CRC of stage III, with lymph node metastasis and deeper invasion (P<0.05). The depletion of PTEN was significantly correlated with the loss of p27 (P<0.001) and with the increased expression of Cyclin D1 (P<0.001). PTEN(−) and/or p27(−) expression was significantly correlated with Cyclin D1(+) expression (P<0.05). Combined PTEN(−)/p27(−)/Cyclin D1(+) expression was correlated with a significant decrease in overall survival time (P<0.05). Combined p27(−) and Cyclin D1(+) expression indicated a worse overall survival time than other combined expression patterns. These findings indicate that the single expression of PTEN(−), p27(−) and Cyclin D1(+) and the combined detection of p27(−) and Cyclin D1(+) may be used as prognostic markers for overall survival time in CRC.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

See 2 more Smart Citations

Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post-operative stage II and III colorectal cancer

Liang

et al. 2014

Oncology Letters

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“…The degree of p21 immunoreactivity is assumed to reflect the degree of expression of the normal p21 gene and serves as a useful tool for assessing its function (Goan et al, 2005). Its expression has been reported to be increased in cutaneous squamous cell carcinoma (Stoyanova et al, 2012), non-small-cell lung carcinoma (Groeger et al, 2000), head and neck cancer (Kapranos et al, 2001), and hepatocellular carcinoma (Zhang et al, 2009) but decreased in colorectal carcinoma (Al-Maghrabi et al, 2012) and ovarian carcinoma (Yan et al, 2004). Its expression has been reported to be increased in cutaneous squamous cell carcinoma (Stoyanova et al, 2012), non-small-cell lung carcinoma (Groeger et al, 2000), head and neck cancer (Kapranos et al, 2001), and hepatocellular carcinoma (Zhang et al, 2009) but decreased in colorectal carcinoma (Al-Maghrabi et al, 2012) and ovarian carcinoma (Yan et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Expression of cell-cycle regulators p53, p27, and p21 in mucoepidermoid and adenoid cystic carcinomas of the minor salivary glands

Talaat¹

2013

Egyptian Journal of Pathology

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Expression of cell-cycle regulators p53, p27, and p21 in mucoepidermoid and adenoid cystic carcinomas of the minor salivary glands Iman M. TalaatBackground The orderly progression of cells through different phases of the cell cycle is orchestrated by various molecules and proteins. p53 plays a crucial role in stress response and tumor suppression. It is a unique cellular processor that integrates signals from various pathways in order to coordinate cell proliferation, differentiation, and apoptosis. p21 WAF1/CIP1 and p27 have key positions in cellcycle regulations, leading to arrest of cell proliferation. They enable a repair process of DNA damage. In several human tumors, a loss of these proteins is associated with poor clinical outcome. Despite recent progress in molecular medicine, there is still a paucity of data on the involvement of cell-cycle regulatory proteins in the pathogenesis of salivary gland tumors.Aim The present work was performed to assess the immunohistochemical expression of p53, p27, and p21 in 15 patients with mucoepidermoid carcinomas (MECs) and adenoid cystic carcinomas (ACCs) of the minor salivary glands and their possible correlation with histopathologic grading.Results The present study included eight patients with ACC and seven patients with MEC. Most of the ACC patients (62.5%) showed positive reaction for p53, whereas only 25% were immunoreactive to p21. Among the seven examined MEC patients, the overall expression of p53 was detected only in those with high-grade tumors. With respect to p21, a moderate reaction was detected in a patient with low-grade MEC. In contrast, immunoreactivity to the p27 protein was detected only in low-grade tumors.Conclusion The cell-cycle regulatory protein p53 was highly expressed in high-grade neoplasms, whereas the reverse was noticed in the case of p27. These findings have a strong prognostic impact. p21 overexpression may be a useful prognostic marker when evaluated in conjunction with p53 status.

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Metformin and thymoquinone co‐treatment enhance 5‐fluorouracil cytotoxicity by suppressing the PI3K/mTOR/HIF1α pathway and increasing oxidative stress in colon cancer cells

et al. 2023

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This study investigated the chemotherapeutic effects of 5‐fluorouracil (5‐FU), metformin (Met), and/or thymoquinone (TQ) single/dual/triple therapies in the HT29, SW480 and SW620 colon cancer (CRC) cell lines. Cell cycle/apoptosis were measured by flow cytometry. The gene and protein expression of apoptosis (PCNA/survivin/BAX/Cytochrome‐C/Caspase‐3) and cell cycle (CCND1/CCND3/p21/p27) molecules, the PI3K/mTOR/HIF1α oncogenic pathway, and glycolysis regulatory enzymes were measured by quantitative‐PCR and Western blot. Markers of oxidative stress were also measured by colorimetric assays. Although all treatments induced anti‐cancer effects related to cell cycle arrest and apoptosis, the triple therapy showed the highest pro‐apoptotic actions that coincided with the lowest expression of CCND1/CCND3/PCNA/survivin and the maximal increases in p21/p27/BAX/Cytochrome‐C/Caspase‐3 in all cell lines. The triple therapy also revealed the best suppression of the PI3K/mTOR/HIF1α pathway by increasing its endogenous inhibitors (PTEN/AMPKα) in all cell lines. Moreover, the lowest expression of lactate dehydrogenase and pyruvate dehydrogenase kinase‐1 with the highest expression of pyruvate dehydrogenase were seen with the triple therapy, which also showed the highest increases in oxidative stress markers (ROS/RNS/MDA/protein carbonyl groups) alongside the lowest antioxidant levels (GSH/CAT) in all cell lines. In conclusion, this is the first study to reveal enhanced anti‐cancer effects for metformin/thymoquinone in CRC that were superior to all monotherapies and the other dual therapies. However, the triple therapy approach showed the best tumoricidal actions related to cell cycle arrest and apoptosis in all cell lines, possibly by enhancing oxidative glycolysis and augmenting oxidative stress through stronger modulation of the PI3K/mTOR/HIF1α oncogenic network.

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Expression of Cell Cycle Regulators P21 and P27 as Predictors of Disease Outcome in Colorectal Carcinoma

Cited by 26 publications

References 35 publications

Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post-operative stage II and III colorectal cancer

Concomitant depletion of PTEN and p27 and overexpression of cyclin D1 may predict a worse prognosis for patients with post-operative stage II and III colorectal cancer

Expression of cell-cycle regulators p53, p27, and p21 in mucoepidermoid and adenoid cystic carcinomas of the minor salivary glands

Metformin and thymoquinone co‐treatment enhance 5‐fluorouracil cytotoxicity by suppressing the PI3K/mTOR/HIF1α pathway and increasing oxidative stress in colon cancer cells

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