Prognostic Importance of Cell Cycle Regulators Cyclin D1 (CCND1) and Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B/p27) in Sporadic Gastric Cancers

Abstract

Background. Gastric cancer is known for a notable variety in the course of the disease. Clinical factors, such as tumor stage, grade, and localization, are key in patient survival. It is expected that molecular factors such as somatic mutations and gene amplifications are also underlying tumor biological behavior and may serve as factors for prognosis estimation. Aim. The purpose of this study was to examine gene amplifications from a panel of genes to uncover potential prognostic marker candidates. Methods. A panel of gene amplifications including 71 genes was tested by multiplex ligation-dependent probe amplification (MLPA) technique in 76 gastric cancer samples from a Caucasian population. The correlation of gene amplification status with patient survival was determined by the Kaplan-Meier method. Results. The amplification of two cell cycle regulators, CCND1 and CDKN1B, was identified to have a negative prognostic role. The medial survival of patients with gastric cancer displaying amplification compared to patients without amplification was 192 versus 725 days for CCND1 (P = 0.0012) and 165 versus 611 days for CDKN1B (P = 0.0098). Conclusion. Gene amplifications of CCND1 and CDKN1B are potential candidates to serve as prognostic markers for the stratification of patients based on the estimate of survival in the management of gastric cancer patients.

ALX1-related Frontonasal Dysplasia Results From Defective Neural Crest Cell Development and Migration

“…To determine if ALX1 function is required for cell cycle progression, we investigated expression of Cyclin D1 (CCND1), required for the cell cycle G1/S transition, and Cyclin A2 (CCNA2), required for the DNA synthesis during the S-phase, were investigated. Both cyclins are expressed throughout the active cell cycle, from the G1/S transition to the G2/M transition (Minarikova, Benesova et al, 2016, Pagano, Pepperkok et al, 1992. Expression levels of CCND1 and CCNA2 were compared between control and ALX1 165F/165F NCC at passages 2 and 3 post-differentiation.…”

ALX 1‐ related frontonasal dysplasia results from defective neural crest cell development and migration

“…To determine whether ALX1 function is required for cell cycle progression, we investigated expression of Cyclin D1 (CCND1), required for the cell cycle G1/S transition, and Cyclin A2 (CCNA2), required for the DNA synthesis during the S-phase. Both cyclins are expressed throughout the active cell cycle, from the G1/S transition to the G2/M transition (Pagano et al, 1992;Minarikova et al, 2016). Expression levels of CCND1 and CCNA2 were compared between control and ALX1 165F/165F NCC at passages 2 and 3 post-differentiation.…”

Molecular profiling of colorectal cancer in a genetically admixed Hispanic population

“…For CRC, it has been reported that the absence or reduction of CDKN1B expression is associated with a poor prognosis 35 . In contrast, CDKN1B gene amplification is associated with poor prognosis for gastric carcinomas 36 . High CDKN1B expression predicts sensitivity to hormone therapies and chemotherapy in luminal breast cancer patients, while its downregulation predicts resistance to radiotherapy and anti‐ERBB2 therapies 37 .…”