Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 21:13:603-611.
doi: 10.2147/RRU.S326249. eCollection 2021.

Expression of L-Type Amino Acid Transporter 1 is a Predictive Biomarker of Intravesical Recurrence in Patients with Non-Muscle Invasive Bladder Cancer

Harutake Sawazaki  1   2 , Yuichi Arai  3 , Yuji Ito  4 , Kimiya Sato  5 , Hitoshi Tsuda  5 , Takashi Yamaga  2 , Hiroyuki Sakurai  2
Affiliations

Expression of L-Type Amino Acid Transporter 1 is a Predictive Biomarker of Intravesical Recurrence in Patients with Non-Muscle Invasive Bladder Cancer

Harutake Sawazaki et al. Res Rep Urol. .

Abstract

Purpose: L-type amino acid transporter 1 (LAT1), a Na+-independent amino acid transporter, is highly expressed in various cancer types. We evaluated the prognostic value of LAT1 expression in non-muscle-invasive bladder cancer (NMIBC).

Patients and methods: We retrospectively reviewed 119 consecutive patients who underwent initial transurethral resection of bladder tumor. Of these, 75 patients with NMIBC were included in this study. Patients were classified into two groups according to the proportion of LAT1-positive cells, as determined by immunohistochemistry. Associations between LAT1 expression and clinicopathological factors were analyzed. Cox multivariate analyses were performed to identify independent predictors of intravesical recurrence (IVR). The LAT1 integrated risk model was compared with the European Organization for Research and Treatment of Cancer (EORTC) risk model to evaluate the predictive ability for IVR based on the c-index.

Results: The median follow-up was 37 months. Twenty-eight patients (37.3%) had IVR. LAT1 expression was not correlated with any other clinicopathological factors. Patients with high LAT1 expression had a worse IVR-free survival than that of patients with low LAT1 expression (P = 0.038). Cox multivariate analyses indicated that tumor multiplicity and high LAT1 expression were independent predictors of IVR. The LAT1 integrated risk model had a significantly improved performance over the EORTC model for assessing recurrence risk (c-index: 0.695, improvement: 0.091, P = 0.001). When patients were stratified into three groups according to the score calculated by the LAT1 integrated risk model, the 2-year IVR-free survival rates were 93.3% in patients with 0 points, 66.9% for those with 2 points, and 37.5% for those with 4 points.

Conclusion: High LAT1 expression was an independent predictor of IVR in patients with NMIBC. The LAT1 integrated risk model had good predictability for IVR.

Keywords: L-type amino acid transporter 1; intravesical recurrence; non-muscle-invasive bladder cancer; transurethral resection of bladder tumor.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Immunohistochemical staining of LAT1 in bladder urothelial carcinoma. Based on the staining degree, LAT1 expression was classified into three levels. (A) Score 1, where ≤10% of the tumor area is stained. (B) Score 2, where 11–50% of the tumor area is stained. (C) Score 3, where ≥51% of the tumor area is stained. Original magnification, ×200.
Figure 2
Figure 2
(A) Kaplan–Meier survival curves for groups with NMIBC with various LAT1 expression scores. (B) Kaplan–Meier curves stratified by LAT1 expression status (low or high).
Figure 3
Figure 3
Predictive performance of the EORTC risk scoring model and LAT1 integrated risk model for intravesical recurrence (IVR) in patients with NMIBC based on AUC values.
Figure 4
Figure 4
Kaplan–Meier curves for intravesical recurrence (IVR)-free survival of patients with 0, 2, and 4 total points.
See this image and copyright information in PMC

References

    1. Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71(1):96–108. doi:10.1016/j.eururo.2016.06.010 - DOI - PubMed
    1. Babjuk M, Burger M, Comperat EM, et al. European association of urology guidelines on non-muscle invasive bladder cancer (TaT1 and carcinoma in situ) - 2019 update. Eur Urol. 2019;76(5):639–657. doi:10.1016/j.eururo.2019.08.016 - DOI - PubMed
    1. Kamat AM, Hahn NM, Efstathiou JA, et al. Bladder cancer. Lancet. 2016;388(10061):2796–2810. doi:10.1016/S0140-6736(16)30512-8 - DOI - PubMed
    1. Fukuokaya W, Kimura T, Miki J, et al. Red cell distribution width predicts time to recurrence in patients with primary non-muscle-invasive bladder cancer and improves the accuracy of the EORTC scoring system. Urol Oncol. 2020;38(7):638.e15–638.e23. doi:10.1016/j.urolonc.2020.01.016 - DOI - PubMed
    1. Juracek J, Stanik M, Vesela P, et al. Tumor expression of miR-34a-3p is an independent predictor of recurrence in non-muscle-invasive bladder cancer and promising additional factor to improve predictive value of EORTC nomogram. Urol Oncol. 2019;37:184.e1–184.e7. doi:10.1016/j.urolonc.2018.10.014 - DOI - PubMed