RRM1 predicts clinical outcome of high-and intermediate-risk non-muscle-invasive bladder cancer patients treated with intravesical gemcitabine monotherapy

Abstract

Background The expression level of ribonucleotide reductase subunit M1 (RRM1) is closely related to the effect of gemcitabine-based therapy in advanced bladder cancer. However, the value of RRM1 expression in predicting progression-free survival in non-muscle-invasive bladder cancer (NMIBC) patients treated with intravesical gemcitabine chemotherapy has not been elucidated. Methods This study randomly assigned 162 patients to either the RRM1-known group or the unknown group. We collected cancer tissues from 81 patients to evaluate the mRNA expression of RRM1 by using liquid chip technology. All patients were diagnosed and then treated with intravesical gemcitabine monotherapy immediately after transurethral resection of the bladder tumour (TURBT). Results RRM1 expression was high in 21% (17/81) of patients. The RRM1 mRNA level was not correlated with sex, age, weight, performance status, or CUA/EAU risk ( p > 0.05). Progression-free survival (PFS) was significantly longer for patients with low RRM1 expression than for patients with high and unknown RRM1 expression ( p = 0.009). Additionally, the 1- and 2-year relapse rates also differed according to RRM1 expression level. The 1-year relapse rates for RRM1-low, RRM1-high and RRM1-unknown patients were 0, 17.7 and 6.2% ( p = 0.009), while the 2-year relapse rates for these groups were 3.1, 29.4, and 11.1% ( p = 0.005), respectively. Conclusions This preliminary study showed that low RRM1 expression was associated with longer progression-free survival and lower 1-year/2-year relapse rates in NMIBC patients treated with intravesical gemcitabine monotherapy, despite the need for further verification with large sample sizes and considering more mixed factors and biases.

Prognostic and predictive role of a metabolic rate‐limiting enzyme signature in hepatocellular carcinoma

“…RRM1 could regulate metabolization and activity of mitotane 23 . Previous research has demonstrated that higher RRM1 expression is discovered to associated with shorter overall survival in non‐small cell lung cancer (NSCLC), 24 non‐muscle‐invasive bladder cancer (NMIBC) 25 and multiple myeloma patients 26 . UCK2 could convert uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP), promoting metastasis of HCC cells via the STAT3/MMP2/MMP9 signal axis 27 .…”

Polymorphisms in the CYP2A6 and ABCC4 genes are associated with a protective effect on chronic myeloid leukemia in the Brazilian Amazon population

“…Over the years, these polymorphisms have been associated with different cancers and other complex diseases. The RRM1 gene, for example, has been related to a high degree of sensitivity to oncological chemotherapy (Yang et al, 2019 ; Zhao et al, 2012 ) and has been identified as a predictive factor in gemcitabine therapy in oncology patients (Jordheim et al, 2011 ). The ABCG2 gene has also been associated with resistance to chemotherapy in the treatment of many types of cancer (Amawi et al, 2019 ; Robey et al, 2018 ).…”

Intravesical gemcitabine as bladder‐preserving treatment for BCG unresponsive non‐muscle‐invasive bladder cancer. Results from a single‐arm, open‐label study

“…Furthermore, we did not use any stratification of risk by using biomarkers or molecular characterization 28 . Yang et al investigated the predictive role of Ribonucleotide reductase subunit M1 (RRM1) mRNA in patients who received gemcitabine 29 . A total of 1000 mg of gemcitabine was diluted in 40 mL of saline solution, and patients received weekly instillations for eight consecutive weeks and once a month for 1 year.…”