Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma

Abstract

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.

Retinoic acid, an essential component of the RP organizer, promotes the spatio-temporal segregation of dorsal neural fates

“…C1QTNF3, known as an anti-inflammatory cytokine 46,68,69 , plays a role in stimulating macrophage chemotaxis during adipose tissue remodelling 70 . Intriguingly, it is one of the 12 prognostic genes linked to recurrence-free survival in human cutaneous melanoma 71 and is a significant gene associated with pigmentary traits 72 . Our analysis has revealed that late-emigrating, C1QTNF3 + bridge cells co-express both glial and melanocyte genes, excluding neuronal genes.…”

Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette–Guérin Immunotherapy of Bladder Cancer

“…Baseline levels of CD79a + B cells before BCG treatment predict poor treatment outcomes in male and female NMIBC patients [53], suggesting that the expansion of exhausted immune cell populations, including atypical B cells, may contribute to early disease recurrence [53]. Paradoxically, while the presence of tertiary lymphoid structures (TLS) is typically associated with improved cancer outcomes [54,55], a recent study indicated that pre-BCG TLS presence is a negative prognostic factor in NMIBC [56]. Moreover, B cell depletion increased the production of IFNγ/IL-2 and IL-13 and the intratumoral levels of CD8A, CXCL10, CXCL9, and BATF3 in response to BCG treatment [56], which is consistent with CTL recruitment and a shift toward the desirable Th1/CTL-dominated immune landscape [56].…”