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

Abstract

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.

Association of CCND1 overexpression with KRAS and PTEN alterations in specific subtypes of non-small cell lung carcinoma and its influence on patients’ outcome

“…Different studies have shown that wild type PTEN prevented the increase in nuclear localization of cyclin D1 and induced G1 cell cycle arrest [36][37][38]8]. This is in accordance with the results obtained on human colorectal and breast carcinoma samples which revealed that depletion of PTEN significantly correlated with increased cyclin D1 expression [39,40]. However, other studies on breast, ovarian, and invasive ductal carcinoma samples did not report such association between PTEN and cyclin D1 [41][42][43].…”

TLE4 promotes colorectal cancer progression through activation of JNK/c-Jun signaling pathway

“…Recently, it was reported that TLE4 could repress P27Kip1 with Cux1 during kidney development [ 23 ]. P27Kip1 is associated with the progression and outcomes of diverse malignancies including CRC [ 24 – 30 ] and can be directly regulated by JNK/c-Jun at transcriptional level and posttranslational levels [ 31 – 33 ]. The oncogene c-Jun is frequently activated in various cancers to promote cell proliferation and tumor growth [ 34 , 35 ].…”

A clinical study on the expression of PTEN in renal cell carcinoma in children

“…PTEN can regulate the expression of cyclin-dependent protein kinase (CDK). Overexpression of PTEN can dephosphorylate substrate retinoblastoma protein (pRb), and moreover combine with transcription factor E2F to significantly reduce cell proliferative potential (23). Some studies have shown that (17,24) PTEN/PI3K/AKT cell signaling pathway can activate kinase system, and then regulates expression of multiple cytokines such as VEGF and hypoxia inducible factor 1α (HIF-1α), so as to participate in tumorigenesis.…”