As such, the final model accounts for age at diagnosis, gender, race, and stage as you possibly can predictors for KLF4 status (Table 4)

As such, the final model accounts for age at diagnosis, gender, race, and stage as you possibly can predictors for KLF4 status (Table 4). odds of KLF4 expression in higher stages of tumors. In both univariate and multivariate analyses, KLF4 was a significant predictor of survival and recurrence. == Conclusions == KLF4 expression is usually significantly down-regulated in colon cancer and loss of KLF4 is an impartial predictor of survival and recurrence. == Impact == These findings suggest that KLF4 may serve as a prognostic biomarker for colon cancer. Keywords:KLF4, Colon Cancer, Tissue microarray, Survival, Recurrence == INTRODUCTION == Despite substantial advances in the early diagnosis and treatment of colorectal cancer, it remains a disease with both high morbidity and mortality. Approximately 150,000 new cases of colon cancer were diagnosed last year in the United States, making it the fourth most common cancer diagnosed in men and women (1). It is also the second most common cause of cancer-related death despite a recent reduction in mortality due to increased testing and improvements in treatment for late-stage cancer (2). Studies have recognized mutations in tumor CHPG sodium salt suppressor genes and oncogenes that result in dysregulation of numerous pathways leading to colorectal carcinogenesis (3,4). Nonetheless, future research in colorectal cancer depends on the ability to conduct research relative to potential applications of available data, translate the mechanistic data into the clinical arena, and evaluate markers impartial of established clinicopathologic predictors of the disease. Biomarker research in colorectal cancer is becoming increasingly popular for a variety of clinical and research applications. Precise biomarkers may be useful as a surrogate endpoint in preliminary studies, for the stratification of patients in clinical trials, and in the refinement of disease prognosis. The argument surrounding the role of chemotherapuetics in American Joint Committee on Cancer (AJCC) stage II colon cancer provides an example of such an software. Within the past decade, a number of new systemic treatments for colon cancer, including oral fluropyrimidines, oxaliplatin, and irinotecan, have been shown to improve overall and disease-free survival in stage III cancer patients (5). Unlike patients with third stage cancer, current recommendations by the American Society of Clinical Oncology (ASCO) do not promote the program use of chemotherapeutics in stage II cancer (6). Though no clinical trial has confirmed overall benefit of adjuvant therapy in stage II, it is hypothesized that up to twenty percent of patients with a risk of recurrence similar to that of stage III disease, would have benefited from chemotherapuetics (5). Currently, the ASCO suggests that patients with inadequately sampled nodes, T4 lesions, CHPG sodium salt perforation, or poorly differentiated histology, should at least be considered for such treatment at the discretion of the treating physician and patient (6). However, no studies have evaluated the benefit of such a recommendation or whether the suggested criteria correctly predict recurrence risk. Biomarkers may prove especially useful in further stratifying stage II patients into those who have a high risk of recurrence and those who do notthe former group being more likely to benefit from chemotherapuetics. Several biomarkers such as S-phase fractions and vascular endothelial growth factor expression have been evaluated in this regard (7,8). Krppel-like factors (KLFs) are a family of evolutionarily conserved mammalian zinc finger transcription factors named for their homology with Krppel, aDrosophilia melanogasterprotein (9). KLFs are involved in a diverse array of fundamental biological processes including proliferation, differentiation, development, and apoptosis (1012). Among the KLF family, the Krppel-like factor 4 (KLF4; also called gut-enriched Krppel-like factor or GKLF) was one of the first recognized (13,14). In addition to regulating many important physiologic processes, CHPG sodium salt KLF4 has been shown to play a role in pathological conditions such as cancer and inflammation (1520). More recently, KLF4 was shown to play a crucial role in the reprogramming of somatic cells into induced pluripotent stem cells (2125). Expression of KLF4 is usually enriched in epithelial tissues including the gut (13,14). In the intestine, KLF4 is usually highly expressed in the postmitotic, terminally differentiated epithelial cells at the luminal surface (26,27).In vitro, KLF4 inhibits proliferation by blocking cell cycle progression at the G1/S boundary (28). In addition, KLF4 mediates the cell cycle checkpoint functions of the tumor suppressor p53 following DNA damage (2931). Moreover, loss of expression of KLF4 due to several reasons including loss of heterozygosity, promoter Rabbit Polyclonal to AIBP hypermethylation, and CHPG sodium salt loss-of-function mutations has been documented in a small set of colorectal cancer specimens (32). This tumor suppressive effect of KLF4 is usually supported byin vivoevidence in which mice heterozygous forKlf4manifest CHPG sodium salt increased tumor burden when bred to theApcMinmice that are genetically predisposed to intestinal adenoma formation (17). From a mechanistic perspective, KLF4 inhibits Wnt signaling, a key pathway in colorectal carcinogenesis, by inhibiting the activity of -catenin, a mediator of.