Prognostic Value of Combined; Cox-2, Cyclin D1 and P21 Expression in Colorectal Cancer (CRC) Patients: An Immunohistochemical Study

Abstract

Background: Cyclooxygenase (COX) is a rate limiting enzyme in synthesis of prostanoids pathway and it has 2 isoforms (COX-1 and COX-2). It has many biological roles in inflammation and oncogenesis. Cox-2 was incriminated in performing disturbances in the cell cycle control in CRC, but its role of in CRC needs clarification of the mechanisms by which Cox-2 might affect the process of colorectal carcinogenesis. Cyclin D1 is an oncogene that regulates G1 phase progression to S phase of the cell cycle. Its stimulatory role on cell cycle is antagonized by Cyclin D1-dependent kinase (CDK) inhibitors like p21. P21 plays an essential role in cell cycle regulation; it may have a pro-apoptotic or an antiapoptotic role in cancer. P21 was found to have many roles in cancer; invasion metastases, cellular senescence and stem cells aging. The roles of combined expression of Cox-2, Cyclin D1 and P21 in CRC tissues and their role of prognosis and patients survival are not sufficiently clarified. Aim of the Study: To evaluate tissue expression of Cox-2, Cyclin D1 and P21 in CRC and to correlate such expression with pathological parameters, clinical and prognostic data of the patients. Methods: Cox-2, Cyclin D1 and P21 are evaluated in colon cancer tissues. Correlations between their level of expressions pathological parameters, clinical and prognostic data of patients were analyzed. Results: Cox-2, Cyclin D1 over-expression was associated with higher grade, higher incidence of occurrence of lymph node & distant metastasis and advanced stage (P = 0.000). Cox-2 was related to higher tumor recurrence rate (P = 0.04) and decreased overall patients survival rate (p = 0.002). (r correlation coefficient = +0.987). Conclusion: Cox-2 and Cyclin D1 are markers of poor prognosis colon cancer patients.

AMP‐kinase inhibitor dorsomorphin reduces the proliferation and migration behavior of colorectal cancer cells by targeting the AKT/mTOR pathway

“…A large number of malignancies have shown overexpression of cyclin D1 such as breast, bladder, lung, pancreatic, and specifically colorectal cancer . Moreover there is growing body of data showing that the association of Cyclin D1 with CRC prognosis . Our data indicated that dorsomorphin decreased the levels of p‐AKT, p‐70s6k, and cyclin D1.…”

Interactions of Colorectal Cancer, Dietary Fats, and Polymorphisms of Arachidonate Lipoxygenase and Cyclooxygenase Genes: A Literature Review

“…Prostaglandins are upregulated in colorectal cancer, and it was reported that genetic polymorphisms in both COX1 and COX2 are associated with CRC ( 27 , 37 ). COX2 is involved in cell cycle control, and increased expression of COX-2 in CRC patients compared to normal controls indicates its possible role in the progression of CRC ( 40 ). COX2 influences cancer progression by increasing prostaglandin production, preventing tumor cell apoptosis, cell proliferation, and tumor angiogenesis ( 41 ).…”

Molecular and genetic features of colorectal carcinoma: pathomorphological demonstration of clinical cases and literature review

“…Окрiм згаданого вище, у контекстi p21 особливий iнтерес привертає дволанцюгова активна РНК (p21-saRNA-322), здатна, не задiюючи р53, активувати експресiєю р21 для iндукцiї завершення клiтинного циклу, що може незабаром стати однiєю iз терапевтичних альтернатив лiкування CRC [29]. Згiдно даних дослiджень, висока експресiя р21 корелює iз меншим розмiром пухлини, низьким ступенем злоякiсностi, вiдсутнiстю метастазiв у реґiонарнi лiмфатичнi вузли та вiдсутнiстю або ранньою стадiєю дистантних метастазiв [30], що робить р21 потенцiйним предитором кращого прогнозу при CRC. При цьому у iншому дослiдженнi нi прямого, нi зворотного зв'язку р21 iз стадiєю, ступенем диференцiювання, залученням у пухлинний процес лiмфатичних вузлiв та прогнозом для хворого не виявлено [31].…”