Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.

Article  PubMed  Google Scholar 

Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, Sher X, Liu XQ, Lu H, Nebozhyn M et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 2018, 362(6411).

Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA, Kurzrock R. Tumor Mutational Burden as an independent predictor of response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017;16(11):2598–608.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tran L, Xiao JF, Agarwal N, Duex JE, Theodorescu D. Advances in bladder cancer biology and therapy. Nat Rev Cancer. 2021;21(2):104–21.

Article  CAS  PubMed  Google Scholar 

Kanai Y. Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacol Ther. 2022;230:107964.

Article  CAS  PubMed  Google Scholar 

Honjo H, Kaira K, Miyazaki T, Yokobori T, Kanai Y, Nagamori S, Oyama T, Asao T, Kuwano H. Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma. J Surg Oncol. 2016;113(4):381–9.

Article  CAS  PubMed  Google Scholar 

Kaira K, Nakamura K, Hirakawa T, Imai H, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Tsukamoto N, Oyama T, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors. Am J Transl Res. 2015;7(6):1161–71.

PubMed  PubMed Central  Google Scholar 

Kaira K, Sunose Y, Ohshima Y, Ishioka NS, Arakawa K, Ogawa T, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, et al. Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer. BMC Cancer. 2013;13:482.

Article  PubMed  PubMed Central  Google Scholar 

Ohkawa M, Ohno Y, Masuko K, Takeuchi A, Suda K, Kubo A, Kawahara R, Okazaki S, Tanaka T, Saya H, et al. Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy. Biochem Biophys Res Commun. 2011;406(4):649–55.

Article  CAS  PubMed  Google Scholar 

Cormerais Y, Giuliano S, LeFloch R, Front B, Durivault J, Tambutté E, Massard PA, de la Ballina LR, Endou H, Wempe MF, et al. Genetic disruption of the multifunctional CD98/LAT1 Complex demonstrates the key role of essential amino acid transport in the control of mTORC1 and Tumor Growth. Cancer Res. 2016;76(15):4481–92.

Article  CAS  PubMed  Google Scholar 

Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, Nikula CJ, Dexter A, Murta T, Race AM, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet. 2021;53(1):16–26.

Article  CAS  PubMed  Google Scholar 

Nagamori S, Wiriyasermkul P, Okuda S, Kojima N, Hari Y, Kiyonaka S, Mori Y, Tominaga H, Ohgaki R, Kanai Y. Structure-activity relations of leucine derivatives reveal critical moieties for cellular uptake and activation of mTORC1-mediated signaling. Amino Acids. 2016;48(4):1045–58.

Article  CAS  PubMed  Google Scholar 

Kim DK, Kanai Y, Choi HW, Tangtrongsup S, Chairoungdua A, Babu E, Tachampa K, Anzai N, Iribe Y, Endou H. Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells. Biochim Biophys Acta. 2002;1565(1):112–21.

Article  CAS  PubMed  Google Scholar 

Geier EG, Schlessinger A, Fan H, Gable JE, Irwin JJ, Sali A, Giacomini KM. Structure-based ligand discovery for the large-neutral amino acid transporter 1, LAT-1. Proc Natl Acad Sci U S A. 2013;110(14):5480–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu J, Yu A, Othmane B, Qiu D, Li H, Li C, Liu P, Ren W, Chen M, Gong G, et al. Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer. Theranostics. 2021;11(7):3089–108.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mermel CH, Schumacher SE, Hill B, Meyerson ML, Beroukhim R, Getz G. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 2011;12(4):R41.

Article  PubMed  PubMed Central  Google Scholar 

Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, Netto GJ, Qin ZS, Kumar S, Manne U, et al. UALCAN: an update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou Y, Zeng P, Li YH, Zhang Z, Cui Q. SRAMP: prediction of mammalian N6-methyladenosine (m6A) sites based on sequence-derived features. Nucleic Acids Res. 2016;44(10):e91.

Article  PubMed  PubMed Central  Google Scholar 

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 2003;31(1):258–61.

Article  Google Scholar 

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.

Article  PubMed  Google Scholar 

Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B, Liu XS. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48(W1):W509–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Finotello F, Mayer C, Plattner C, Laschober G, Rieder D, Hackl H, Krogsdam A, Loncova Z, Posch W, Wilflingseder D, et al. Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data. Genome Med. 2019;11(1):34.

Article  PubMed  PubMed Central  Google Scholar 

Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Sautès-Fridman C, Fridman WH, et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016;17(1):218.

Article  PubMed  PubMed Central  Google Scholar 

Li B, Severson E, Pignon JC, Zhao H, Li T, Novak J, Jiang P, Shen H, Aster JC, Rodig S, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. 2016;17(1):174.

Article  PubMed  PubMed Central  Google Scholar 

Xu L, Deng C, Pang B, Zhang X, Liu W, Liao G, Yuan H, Cheng P, Li F, Long Z, et al. TIP: a web server for resolving Tumor Immunophenotype profiling. Cancer Res. 2018;78(23):6575–80.

Article  CAS  PubMed  Google Scholar 

Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, Albright A, Cheng JD, Kang SP, Shankaran V, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930–40.

Article  PubMed  PubMed Central  Google Scholar 

Hu J, Othmane B, Yu A, Li H, Cai Z, Chen X, Ren W, Chen J, Zu X. 5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer. BMC Med. 2021;19(1):289.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484–92.

Article  CAS  PubMed  Google Scholar 

He Z, Zheng H, Wang G, Jiang W, Zhao X, Sun X. Leucine promotes bone formation in osteoporotic mice by activating Wnt/β-catenin pathway. Panminerva Med. 2023;65(1):124–5.

Article  PubMed  Google Scholar 

Majidpoor J, Mortezaee K. The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives. Clin Immunol. 2021;226:108707.

Article  CAS  PubMed  Google Scholar 

Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Dominguez Escrig JL, Gontero P, Liedberg F, Masson-Lecomte A, Mostafid AH, et al. European Association of Urology Guidelines on non-muscle-invasive bladder Cancer (Ta, T1, and carcinoma in situ). Eur Urol. 2022;81(1):75–94.

Article  PubMed  Google Scholar 

Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G, Hernández V, Linares Espinós E, Lorch A, Neuzillet Y, et al. European Association of Urology Guidelines on muscle-invasive and metastatic bladder Cancer: Summary of the 2020 guidelines. Eur Urol. 2021;79(1):82–104.

Article  CAS  PubMed  Google Scholar 

Niglio SA, Jia R, Ji J, Ruder S, Patel VG, Martini A, Sfakianos JP, Marqueen KE, Waingankar N, Mehrazin R, et al. Programmed Death-1 or programmed death Ligand-1 blockade in patients with platinum-resistant metastatic Urothelial Cancer: a systematic review and Meta-analysis. Eur Urol. 2019;76(6):782–9.

Article