Abstract PR02: Diagnostic and prognostic utility of urinary creatine riboside for early stage non-small cell lung cancer
Authors: Oike Takahiro , Kanke Yasuyuki , Parker Amelia , Haznadar Majda , Krausz Kristopher W. , Bowman Elise D. , Robles Ana I. , Gonzalez Frank J. , Harris Curtis C. 
Published: February 2019

Abstract
Lung cancer is the leading cause of cancer-related death worldwide. With the advent of low-dose computed tomography screening, it is expected that the number of lung cancers diagnosed at an early stage will rise sharply. The recommended treatment for stage I non-small cell lung cancer (NSCLC) patients is tumor resection, which may be followed by chemotherapy in patients with pathologically high-risk, margin-negative stage IB tumors. Still, up to 30% surgically treated stage I patients experience recurrence leading to death. Therefore, biomarkers that molecularly categorize stage I patients after tumor resection and stratify high-risk patients who may benefit from adjuvant chemotherapy would lead to improved clinical management. We previously conducted metabolomic profiling of urines collected from 469 NSCLC patients and 536 population controls using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS) and found that creatine riboside, a novel metabolite identified by the study, is significantly elevated in stage I and II NSCLC patients compared to controls. We also found that creatine riboside levels are 19-fold higher in tumor tissues compared to adjacent normal lung tissues (P&lt;0.00001) in 48 NSCLC cases. We further discerned that creatine riboside levels in tumor tissues correlate significantly with those in urine (P&lt;0.0001, R2=0.87 by Spearman’s rank order test). These data indicate that creatine riboside may be a product of deregulated tumor metabolism that is detectable in urine, making urinary creatine riboside a potentially useful liquid biopsy biomarker for surveillance after surgery in early stage NCSLC patients. To further evaluate the utility of creatine riboside as a liquid biopsy biomarker, urines from 34 stage I and II NSCLC patients from Lung Cancer Biospecimen Resource Network (LCBRN), collected at the time of diagnosis and 6, 12, 18 and 24 months after surgery, were evaluated in the current study. The urinary levels of creatine riboside were quantitated using UPLC-MS/MS and were analyzed for association with cancer-specific survival and disease-free survival. As a result, in non-recurrent cases (n=23), creatine riboside levels showed a significant decreasing trend over 24 months after surgery (P=0.03). These data further support previous evidence that creatine riboside is a product of deregulated tumor metabolism that can be detected in urine. In addition, Kaplan Meier survival estimates demonstrated that high creatine riboside levels at the time of diagnosis correlated significantly with worse cancer-specific survival and disease-free survival (P=0.005 and P=0.003, respectively). In summary, urinary creatine riboside may have potential as a liquid biopsy biomarker for early stage NSCLC that aids surveillance after surgery as well as to stratify patients with worse prognosis.
This abstract is also being presented as Poster A18.
Citation Format: Takahiro Oike, Yasuyuki Kanke, Amelia Parker, Majda Haznadar, Kristopher W. Krausz, Elise D. Bowman, Ana I. Robles, Frank J. Gonzalez, Curtis C. Harris. Diagnostic and prognostic utility of urinary creatine riboside for early stage non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr PR02.