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In patients with bladder cancer, lactylation score may predict survival and efficacy of immune checkpoint inhibitor treatment, according to researchers.

Lactylation genes have significant control over the immune microenvironment of tumors and treatment outcomes in patients with bladder cancer, according to a study published online in Archivio Italiano di Urologia e Andrologia.

“Lactylation is a type of chemical modification involving the introduction of lactyl groups to a molecule, which can affect the interactions between tumor cells and their microenvironment,” explained Kemal Sarica, MD, PhD, of Biruni University Medical School, Istanbul, Turkey, and colleagues.

Lactylation has emerged as a potential target for novel cancer therapies that modify lactate signaling pathways and disrupt tumor progression. However, the role of lactylation in bladder cancer has been unclear, researchers explained.

Lactylation Investigation

The team investigated two lactylation-related gene subtypes in bladder cancer using unsupervised clustering and compared clinical features, differentially expressed genes (DEGs), pathways, and immune cell infiltration.

According to the study, DEG analysis revealed 11 lactylation genes associated with overall survival: CLIC3, S100A8, SPHK1, RCN3, CDA, LGALS1, TBX3, AEBP1, TP53INP1, KRT16, and TCIRG1. Investigators used the prognostic genes to create a lactylation score for quantifying patient risk.

“Our results demonstrated that patients with a high lactylation score tended to have a worse survival period and increased immune cell infiltration level,” researchers wrote.

Patients with high lactylation scores had high expression levels of chemokines, chemokine receptors, and immune checkpoints, the study found. The finding suggests that although a high lactylation score may signal a poor prognosis, it may also signal a better response to immune checkpoint inhibitor (ICI) treatment. An analysis of two immunotherapy datasets confirmed the link between high lactylation score and a positive response to ICI treatment.

“This finding is highly valuable in an attempt to predict the efficacy of ICI treatment in a reliable manner in cases with BLCA [bladder cancer],” researchers wrote.

Additional analysis suggested that bladder cancer in patients with a high lactylation score may be resistant to six commonly used chemotherapeutic agents (gemcitabine, cisplatin, vinblastine, doxorubicin, docetaxel, and paclitaxel) and five targeted agents (sunitinib, pazopanib, gefitinib, erlotinib, and tipifarnib).

Future Impact

“All these observations indicated well the vital role of lactylation in clinical practice,” researchers wrote, “which could enable the physicians to potential customization of the applied treatments in BLCA [bladder cancer] patients.”