High clusterin (CLU) mRNA expression levels in tumors of colorectal cancer patients predict a poor prognostic outcome

• Published in: Clinical biochemistry Vol. 75; pp. 62 - 69
• Main Authors: Artemaki, Pinelopi I., Sklirou, Aimilia D., Kontos, Christos K., Liosi, Aikaterini-Anna, Gianniou, Despoina D., Papadopoulos, Iordanis N., Trougakos, Ioannis P., Scorilas, Andreas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Clusterin - genetics; Clusterin - metabolism; Colon cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - pathology; Female; Humans; Male; Middle Aged; Molecular tumor markers; Overall survival; Prognosis; Prognostic biomarkers; Relapse; RNA, Messenger - metabolism; Prognostic biomarkers; Relapse; Molecular tumor markers; Colon cancer; Prognosis; Overall survival
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2019.10.008

•Patients with CLU mRNA-positive colorectal tumors are more prone to relapse.•CLU mRNA levels are enhanced as colorectal tumors progress from TNM stage I to IV.•High CLU mRNA levels in CRC can act as an independent biomarker of tumor recurrence.•CLU mRNA-positive patients are more likely to succumb to CRC. Clusterin (CLU) is a multifunctional intra-/extra-cellular molecular chaperone with indications of serving as a promising prognostic biomarker for colorectal cancer (CRC). Several studies have examined the potential prognostic value of the CLU protein in CRC; however, our research follows an alternative approach, focusing on the CLU mRNA expression. Total RNA from 172 cancerous tissue specimens and 39 paired non-cancerous ones was isolated and 2 μg of this were subjected to reverse transcription with an oligo-dT primer. The single stranded DNA, which was synthesized, was amplified with an in-house developed highly sensitive and precise qPCR method, using specific pair of primers for the CLU molecule. Finally, an extensive biostatistical analysis took place for the assessment of the results. Patients with tumors expressing high CLU mRNA levels had a higher probability for poor outcome (relapse and death), comparing to those with CLU mRNA-negative tumors. This association between CLU mRNA expression status and both disease-free survival (DFS) and overall survival (OS) is evident in Cox regression analysis and is also depicted in the Kaplan-Meier survival curves. Consistently, the aforementioned associations and the CLU mRNA expression levels are significantly enhanced as CRC tumors progress from TNM stage I to IV, further supporting the functional implication of CLU in tumorigenesis. High CLU mRNA levels in CRC tumors can act as a new adverse prognostic biomarker of DFS and OS for CRC, independent of clinicopathological and biological features of the patient.