A pan-tumor description of the genomic, transcriptomic, and immunological landscape of sodium-glucose cotransporter-2 (SGLT2) and association with clinical outcomes.
Year: 2024
Type: conference-abstract
Abstract: 104 Background: SGLT2 has been identified as being overexpressed in a diverse set of cancers. Retrospective data has demonstrated a correlation between the use of SGLT2 inhibitors and a reduced incidence of lung cancer. We explored the association of SGLT2-coding gene SLC5A2 with the transcriptomic, genomic, immunological landscape and outcomes in a subset of solid tumors. Methods: Breast ([N = 5623], HR+HER2- [6044] or TNBC [3040]), Colorectal carcinoma (CRC, 15425), NSCLC ([21603], Adenocarcinoma [AC, 8180] or Squamous Cell Carcinoma [SCC, 3579]), Pancreatic (Panc: 5488) and Prostate (PC: 5500) tumors were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (592 genes or whole exome) and RNA (whole transcriptome). PD-L1+ (22C3: TPS 1% for lung or SP142: 2+, 5% all other), Her2/Neu (+: ≥3+ and > 10%) and HR (ER or PR+: ≥1+ and ≥1%) expression was assessed by IHC. Mutations were defined as pathogenic SNVs/indels (-Mt). SLC5A2-H and -L expression (transcripts per million, TPM) was defined by cancer type as top and bottom quartile, respectively. Cell infiltration was estimated by QuantiSEQ. A transcriptomic signature predictive of response to immunotherapy was applied (T cell-inflamed). The Mann-Whitney U test was applied as appropriate (p < .05, adjusted for multiple comparisons). Real-world overall survival (OS) was obtained from insurance claims and Kaplan-Meier estimates were calculated for molecularly defined patients. Results: SLC5A2 expression varied across cohorts (TNBC: 1.2 TPM, HR+HER2-BC: 1.7, CRC: 2.2, AC: 1.8, SCC: 1.3, Panc: 1.7, PC: 1.7, p < .05). SLC5A2-H had a higher prevalence of FGF3 amplifications in HR+HER2- BC (17.4% -H v 10.4 -L), CRC (1.4 v .45) and PC (4.4 v .89, p < .05 all). KRAS-Mt was more prevalent in SLC5A2-L CRC (41% v 53) as was BRAF-Mt (6 v 14, p < .05 all). There was a lower prevalence of PDL1+ in SLC5A2-H for HR+HER- BC (14% -H v 24 -L), CRC (2 v 6), AC (47 v 68), SCC (50 v 66) and Panc (10 v 19, p < .05 all). All SLC5A2-H tumors had increased Neutrophil, B, NK cell infiltrate (Table) and an increased prevalence of T cell-inflamed tumors (p < .05, all). SLC5A2-H had longer OS v -L in CRC (HR .82 [.76-.88], p <.001), PC (HR .85 [.74-.99], p =.03), HR+HER2- BC (HR .79 [.68-.91], p < .001) and AC (HR .79 [.73-.85], p < .001). Conclusions: SCL5A2-H across all investigated tumors was associated with increased immune infiltrate and a T cell-inflamed phenotype in addition to improved survival in multiple cancer types. Future research on SGLT2 should delineate its role in cancer formation versus its association as a potential positive prognostic marker. [Table: see text]
Source: Journal of Clinical Oncology
Institutions: Jackson Memorial Hospital, University of Miami, Sylvester Comprehensive Cancer Center, Caris Life Sciences (United States), Georgetown University, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, Penn State Milton S. Hershey Medical Center, Universidade Federal do Rio Grande do Sul, Masonic Cancer Center, West Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4401514664