Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma

Abstract

Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher’s exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan–Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29–9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44–19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma’s molecular profile and the body’s immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma.

A novel inflammatory response-related signature predicts the prognosis of cutaneous melanoma and the effect of antitumor drugs

“…Many inflammatory response-related characteristics in the peripheral blood of patients with CM, such as thrombocytosis, leukocytosis, hypoproteinemia, and increased plasma fibrin, have been established in investigations [15,16]. In the overall survival analysis of cancer, clinical systemic inflammatory markers such as neutrophil ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio revealed substantial predictive potential independent of previously identified prognostic variables for CM [17]. The link between inflammatory responserelated genes and CM prognosis, on the other hand, is uncertain [18].…”

Chemical features of melanoma tumor resident TRG CDR3s associated with better survival probabilities

“…Melanoma is among the most, if not the most immunogenic cancer [1], and is among the most responsive to immunotherapy [2]. Both of these facts are likely, or at least partially explained by the large tumor neoantigen loads [3], in turn due to ultraviolet light exposure and insufficient repair of DNA lesions. However, currently available immunotherapies are not comprehensively effective against melanoma [2].…”

A novel inflammatory response-related signature predicts the prognosis of skin cutaneous melanoma and the effect of anti-tumor drugs

“…Many in ammatory response-related characteristics in the peripheral blood of patients with SKCM, such as thrombocytosis, leukocytosis, hypoproteinemia, and increased plasma brin, have been established in investigations [15] [16]. In the overall survival analysis of cancer, clinical systemic in ammatory markers such as neutrophil ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio revealed substantial predictive potential independent of previously identi ed prognostic variables for SKCM [17]. The link between in ammatory response-related genes and SKCM prognosis, on the other hand, is uncertain [18].…”