Prognostic Factor In Melanoma Research Articles

Nomogram Predicts Prognostic Factors for Head and Neck Cutaneous Melanoma: A Population-Based Analysis

BackgroundThe head and neck cutaneous melanoma (HNCM) accounts for 20% of newly diagnosed melanoma. Research on prognostic models for their survival yet remains largely unexplored. This study employed a nomogram approach to develop and validate a predictive model for both overall survival (OS) and disease-specific survival (DSS) in patients with HNCM. MethodsThis study analyzed the HNCM patients diagnosed between 2004 and 2014 from SEER database. To identify independent prognostic factors for HNCM, we integrated results from univariate Cox regression analysis, random survival forests, and LASSO regression with cross-validation. A nomogram was designed and validated based on the identified characteristics to predict the 3-, 5-, and 8-year OS and DSS of patients with HNCM. ResultsAge, Stage, Ulceration, Thickness, Chemotherapy, LN_Metastasis, Radiation were identified as independent prognostic factors. The nomogram achieved a satisfactory performance with C-indices of 0.824(DSS) and 0.757(OS) in the training cohort and 0.827(DSS) and 0.749(OS) in the validation cohort, respectively. The AUC for the OS at 3-, 5-, and 8- years were 0.789, 0.788, and 0.794 for the training cohort, and 0.778, 0.776, and 0.795 for the validation cohort, respectively. For DSS, the AUC at 3-, 5-, and 8- years were 0.859, 0.842, and 0.828 in the training cohort, and 0.864, 0.844, and 0.834 in the validation cohort, respectively. The calibration curve showed that there was a strong correlation between the observed outcomes and the predicted survival probability. ConclusionThis study established and validated predictive nomograms for HNCM patients with robust predictive performance.

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

Assessing the prognostic value of IMDC risk score for nivolumab-treated patients with renal cancer and malignant melanoma.

The response of Renal Cell Cancer (RCC) to tyrosine kinase inhibitors (TKI) has been well established. Although these stratifications have been established for TKI response and prognosis, these parameters have recently been used to predict immunotherapy response in RCC. We aimed to use a combination of clinical parameters of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups and metastatic sites at the time of diagnosis to predict the effectiveness of immune checkpoint inhibitors in malignant melanoma (MM). In this cross-sectional study, we retrospectively analyzed the demographic information, metastatic sites, and IMDC risk group data. The blood parameters were included in the first cycle of nivolumab treatment. The OS was statistically different between the RCC and MM groups in terms of the IMDC. In univariate analysis of stage at diagnosis, CRP levels and bone and bone marrow metastases were confirmed to be prognostic factors in the MM population in terms of OS. Brain metastasis was a prognostic factor for RCC, whereas sex, line of treatment, LDH, bone, and splenic metastasis remained significant in patients with MM in terms of OS. Brain metastasis was prognostic in both cancer types in multivariate analysis in terms of PFS. In addition to brain metastasis, LDH levels and lung, liver, and splenic metastases also affect PFS in patients with MM undergoing nivolumab treatment. In our study, the IMDC was confirmed to be a prognostic factor for MM. The IMDC groups were similar, except for the favorable RCC and MM groups. Different metastatic sites were prognostic, similar to the IMDC risk group in the MM group.

Lower limb cutaneous melanoma surgery: location matters

The anatomical location of cutaneous melanoma is a relevant independent prognostic factor in melanoma. The aim of the study is to know the prognosis of lower limb cutaneous melanoma related to their location within the limb, regardless of the histological type, and if there are any other influencing variables. A real-world data observational study was developed. The lesions were divided depending on the location of the melanoma (thigh, leg and foot). Bivariate and multivariate analysis were performed, and melanoma-specific survival and disease-free survival rates were calculated. When these analysis were done, the results showed that, in melanomas of the lower limb, location on the foot presented a lower melanoma-specific survival rate compared to more proximal locations, and only the anatomical location presents statistical significance to discriminate cases with a higher mortality risk and a lower disease-free survival rate among distal melanomas (mainly on the foot). In conclusion, this study confirms that a more distal location of lower limb cutaneous melanoma is a relevant prognostic factor.Trial registration number NCT04625491 retrospectively registered.

Non-Coding RNA Investigations in Cutaneous Melanoma: A Step forward in Discovering Novel Biomarkers

Non-Coding RNA Investigations in Cutaneous Melanoma: A Step forward in Discovering Novel Biomarkers

Immune Pathways with Aging Characteristics Improve Immunotherapy Benefits and Drug Prediction in Human Cancer.

(1) Background: Perturbation of immune-related pathways can make substantial contributions to cancer. However, whether and how the aging process affects immune-related pathways during tumorigenesis remains largely unexplored. (2) Methods: Here, we comprehensively investigated the immune-related genes and pathways among 25 cancer types using genomic and transcriptomic data. (3) Results: We identified several pathways that showed aging-related characteristics in various cancers, further validated by conventional aging-related gene sets. Genomic analysis revealed high mutation burdens in cytokines and cytokines receptors pathways, which were strongly correlated with aging in diverse cancers. Moreover, immune-related pathways were found to be favorable prognostic factors in melanoma. Furthermore, the expression level of these pathways had close associations with patient response to immune checkpoint blockade therapy in melanoma and non-small cell lung cancer. Applying a net-work-based method, we predicted immune- and aging-related genes in pan-cancer and utilized these genes for potential immunotherapy drug discovery. Mapping drug target data to our top-ranked genes identified potential drug targets, FYN, JUN, and SRC. (4) Conclusions: Taken together, our systematic study helped interpret the associations among immune-related pathways, aging, and cancer and could serve as a resource for promoting clinical treatment.

Prognostic role of microsatellites in melanoma and implications in the American Joint Committee on Cancer classification system: A cohort study

There is limited information on microsatellite survival outcomes in patients with melanoma. To evaluate survival outcomes in patients with microsatellites, assess their role within stage III stratification of the American Joint Committee on Cancer classification, and assess the results of sentinel lymph node biopsies in patients with microsatellites. A retrospective bicenter cohort study from 1998 to 2019 included patients with a diagnosis of invasive cutaneous melanoma. Of a total of 5216 patients, 108 (2.1%) had microsatellites at initial staging. Survival analysis showed that microsatellites were an independent risk factor with decreased overall survival (OS), melanoma-specific survival (MSS), and disease-free survival, with hazard ratios of 1.57, 1.76, and 1.76, respectively. Stratified analysis in patients with stage III melanoma showed a 5-year OS of 35% (95% CI, 17.3%-73.4%) and a MSS of 45% (95% CI, 23.1-87.5) for patients with stage IIIB melanoma with microsatellites. Retrospective design of the study. Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival. Patients with stage IIIB melanoma with microsatellites had worse OS and MSS, whereas patients with stage IIIC melanoma had worse OS but not MSS.

227 Socioeconomic predictors of melanoma Breslow thickness at a Rhode Island academic center

Introduction: Breslow thickness is an important prognostic factor in malignant melanoma (MM). Lower socioeconomic status (SES) has emerged as a predictor of poor prognosis, though few US data relate SES to thickness. Furthermore, few studies investigated neighborhood-level income alongside insurance status and clinicopathological factors of MM. To examine relationships between SES and tumor thickness, we retrospectively reviewed medical and pathology records of MM patients at a Rhode Island academic center.

Major Histotypes in Skin Melanoma: Nodular and Acral Lentiginous Melanomas Are Poor Prognostic Factors for Relapse and Survival.

The histological subtype is not considered one of the major prognostic factors in melanoma, yet it is known to have an impact on survival. The aim of this study was to investigate the clinical significance of histological subtypes and the possible impacts of clinicopathological factors on the course of melanoma patients of all stages. A total of 1017 cutaneous melanoma patients were analyzed retrospectively. Four major melanoma histotypes that were studied in this study were as follows: (1) superficial spreading melanoma (SSM), (2) nodular melanoma (NM), (3) acral lentiginous melanoma (ALM), and (4) lentigo maligna melanoma (LMM). Unlike SSMs and LMMs, there were statistically significant correlations between NMs and ALMs and most aggressive histopathological prognostic indicators, such as higher Clark level ( P = 0.0001), thick Breslow depth ( P = 0.0001), presence of ulceration ( P = 0.0001), and lymphovascular invasion ( P = 0.0001). Furthermore, NMs and ALMs were also associated with advanced clinical stages, that is, node involvement and metastasis. Relapse rates for nonmetastatic melanomas were higher in NMs (39.6%) and ALMs (35.3%) than in SSMs (24.3%) and LMMs (10.3%) ( P = 0.0001). Additionally, 5-year relapse-free survival rates were 90.5%, 70.5%, 55.7%, and 50.5% in LMMs, SSMs, ALMs, and NMs, respectively ( P = 0.0001). Moreover, 5-year overall survival rates plummeted from 84.3% in LMMs to 74.8%, 64.3%, and 46% in SSMs, ALMs, and NMs, respectively ( P = 0.0001). In conclusion, we observed that the histologic subtype was an independent predictor for relapse and outcome for cutaneous melanoma patients. Both NM and ALM had unfavorable prognoses, and they were associated with known poor pathological and clinical indicators.

A novel 7‑hypoxia‑related long non‑coding RNA signature associated with prognosis and proliferation in melanoma.

Hypoxia-related long non-coding RNAs (lncRNAs) are important indicators of the poor prognosis of cancers. The present study aimed to explore the potential relationship between melanoma and hypoxia-related lncRNAs. The transcriptome and clinical data of patients with melanoma were downloaded from The Cancer Genome Atlas database. The prognostic hypoxia-related lncRNAs were screened out using Pearson's correlation test and univariate Cox analysis. As a result, a hypoxia-related-lncRNA signature based on the expression of 7 lncRNAs was constructed, with one unfavourable [MIR205 host gene (MIR205HG)] and six favourable (T cell receptor β variable 11-2, HLA-DQB1 antisense RNA 1, AL365361.1, AC004847.1, ubiquitin specific peptidase 30 antisense RNA 1 and AC022706.1) lncRNAs as prognostic factors for melanoma. Patients with melanoma were divided into high- and low-risk groups based on the risk score obtained. Survival analyses were performed to assess the prognostic value of the present risk model. Potential tumour-associated biological pathways associated with the present signature were explored using gene set enrichment analysis. The CIBERSORT algorithm demonstrated the important role of the hypoxia-related lncRNAs in regulating tumour-infiltrating immune cells. Clinical samples collected from our center partly confirmed our findings. Cell Counting Kit-8 and flow cytometry assays indicated the suppression of proliferation of melanoma cells following inhibition of MIR205HG expression. Indicators of the canonical Wnt/β-catenin signalling pathway were detected by western blotting. The present study demonstrated that MIR205HG could promote melanoma cell proliferation partly via the canonical Wnt/β-catenin signalling pathway. These findings indicated a 7-hypoxia-related-lncRNA signature that can serve as a novel predictor of melanoma prognosis.

Real-world study on characteristics of advanced melanoma patients with sustained complete response (CR) after elective 1st line anti-programmed death-1 (anti-PD1) monotherapy discontinuation.

e21529 Background: Previous reports proved the feasibility of immunotherapy (IT) discontinuation in advanced melanoma (MEL) patients (pts) in case of CR. We aimed to investigate clinical characteristics of pts with sustained CR after elective discontinuation of the 1st line anti-PD1 monotherapy in the real world setting. Methods: This is a multicenter retrospective cohort study. Eligible pts ≥ 18 years with unresectable locally advanced or metastatic primary cutaneous (PC) or unknown primary (UP) MEL with at least one measurable lesion per RECIST version 1.1 at baseline, treated with nivolumab (NIVO) o pembrolizumab (PEMBRO) monotherapy with no previous IT were included. All pts achieved CR to the treatment confirmed by computed tomography (CT) or positron emission tomography (PET-CT) and had at least one imaging study in the follow-up (FU). IT discontinuation was at the discretion of the treating physician. Pts with CR who stopped IT due to toxicity grade (G) 3 and/or 4 were excluded. Information regarding baseline characteristics, survival and immune related adverse events (irAEs) was obtained from patients´ charts. Data cut-off was February 10th 2022. Results: 36 pts treated in 12 hospitals in Spain between October 8th 2015 and October 27th 2021 were identified. Mean age was 66.8 years and mean BMI was 27.4. Twenty eight (77.8%) pts were males and 35 (97.2%) had ECOG PS 0-1. PC melanoma was observed in 33 (91.7%) pts, UP in 3 (8.3%). 35 pts (97.2%) had metastatic disease, with 11 (30.6%) pts with ≥3 metastatic sites. There were 21 (58.4%) pts with stage M1a-M1b disease; only 3 (8.3%) had liver and 2 (5.6%) had brain metastases. Baseline LDH was within normal limits in 28 (77.8%) pts and 31 (86.1%) pts had baseline neutrophil to lymphocyte ratio ≤3. Treatment received: PEMBRO 21 (58.3%), NIVO 15 (41.7%) pts. CR to treatment was confirmed by PET-CT in 27 (75.0%) pts. Median duration of anti-PD1 IT was 23.5 months (range 1.3 - 50.5) and median time to CR was 12.0 months (range 2.2 - 50.2). With the median FU time off treatment of 24.1 months (95% CI 19.4 – 28.8), median progression free survival (PFS) after IT discontinuation has not been reached: estimated PFS at 1 and 2 years were 94.1% and 89.2%, respectively. Estimated overall survival from start of IT at 3 and 4 years were 97.2% and 93.5%, respectively. irAEs G 1-2 were observed in 30 (83.3%) pts and the most common were: vitiligo 8 (22.2%), pruritis 4 (11.1%), other skin toxicity 8 (22.2%), hypothyroidism 5 (13.9%), pneumonitis 3 (8.3%), colitis 5 (13.9%), hepatitis 3 (8.3%), arthralgia 5 (13.9%) and nephritis 3 (8.3%). Conclusions: Our study confirms sustained CR after elective 1st line anti-PD1 monotherapy discontinuation in a cohort of advanced PC and UP MEL pts with favorable established prognostic factors for MEL at baseline. Frequency of irAEs was concordant with previous reports on IT.

Characterization of Aging-Related Genes to Predict Prognosis and Evaluate the Tumor Immune Microenvironment in Malignant Melanoma.

Objective Malignant melanoma (MM) is one of the most malignant types of skin cancer and its incidence and mortality rates are increasing worldwide. Aging is well recognized as a significant risk factor for cancer. However, few studies have analyzed in depth the association between aging-related genes (AGs) and malignant melanoma prognosis with tumor immune microenvironment. Methods Here, we downloaded 471 MM patients from The Cancer Genome Atlas (TCGA) with RNA sequence and clinicopathological data. 58 AGs from the TCGA dataset were examined using Cox regression and the LASSO assay. As a result, a gene signature for aging-related genes was created. The time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its predictive capability. Moreover, we created a nomogram for the clinicopathologic variables and the AGs gene signature to determine overall survival (OS). We also explored the association between three immune checkpoints, immune cell infiltration, and the aging-related gene signature. Results We established an aging risk model to identify and predict the immune microenvironment in malignant melanoma. Then we developed and validated a prognosis risk model using three AGs (CSNK1E, C1QA, and SOD-2) in the GSE65904 dataset. The aging signature was positively associated with clinical and molecular characteristics and can be used as a prognostic factor for malignant melanoma. The low aging risk score was associated with a poor prognosis and indicated an immunosuppressive microenvironment. Conclusions To summarize, we established and validated a model of aging risk based on three aging-related genes that acted as an independent prognostic predictor of overall survival. Besides, it also characterized the immune response in the malignant melanoma microenvironment and could provide a potential indicator of individualized immunotherapy in malignant melanoma.

Epidermal melanoma prognostic factors: a link to paracrine transforming growth factor-β signalling.

Linked Article: Cosgarea et al. Br J Dermatol 2022; 186:694–704.

STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice

BackgroundMyeloid-derived suppressor cells (MDSCs) represent a negative prognostic factor in malignant melanoma. These cells are generated under chronic inflammatory conditions typical of cancer. The transcription factor signal transducer and activator...

The Role of Autophagy-related Proteins of Beclin-1/BECN1, LC3II, and p62/SQSTM1 in Melanoma Tumors

Purpose: The prognosis of melanoma depends on early diagnosis and timely treatment. Autophagy plays a dual role in tumor progression. In the early stages, it prevents tumor formation, while in the advanced stages it promotes tumorigenicity. This study aimed at investigating the role of autophagy in different stages of melanoma and evaluating the relationship between autophagy and clinicopathological factors. Methods: ATG5 and BECN1 genes expression in melanoma tumors were evaluated in a retrospective study of 5 years in the cancer institute of Tehran, Iran. The autophagy-related proteins and the correlation with clinicopathological data were also investigated in a tissue microarray series of 52 melanoma tumors following by immunohistochemical staining for the autophagy-associated proteins p62/SQSTM1 (p62), LC3II and Beclin-1/BECN1. The possibility of autophagy biomarkers was also predicted by ROC curve analysis. Results: ATG5 and BECN1 gene expression decreased in melanoma tumors in comparison with tumor margins. However, BECN1 expression at the protein level increased with tumor progression. The expression of LC3II also raised while the p62 level declined as the tumor progressed, suggesting an increased autophagy activity during tumor development. Furthermore, melanoma ulceration was positively correlated with BECN1, LC3II and p62 expression with p<0.05, though the melanoma mitotic rate and thickness did not significantly correlate with autophagy–related proteins expression. Conclusions: Autophagy-related proteins are suggested as potential prognostic factors in melanoma and could be considered as a therapeutic target.

The efficacy of 99mTc-rituximab as a tracer for sentinel lymph node biopsy in cutaneous melanoma patients.

BackgroundThe sentinel lymph node (SLN) status is a vital prognostic factor for malignant melanoma (MM) patients. There is increasing evidence that a radioactive agent, rather than its combination with blue dye, is sufficient for a SLN biopsy (SLNB). Thus, we discussed the efficacy of 99mTc-rituximab as a tracer in MM patients.MethodsA total of 502 consecutive patients with MM who underwent SLNB were enrolled in this study. All participants were peritumorally injected with 99mTc-rituximab before imaging, and scanned with single-photon emission computed tomography-computed tomography (SPECT-CT) to detect the number and location of the SLN. A gamma detection probe was employed to detect radioactive SLNs in operation. Follow up was conducted to observe whether nodal or distant recurrence occurred.ResultsThe SLNs were successfully imaged via SPECT-CT and harvested from all 502 participants. No drainage tube was indwelled and 32 (6.3%) participants experienced the following complications: seroma (n=26, 5.2%), wound infections or lymphangitis (n=6, 1.2%), sensory nerve injuries (n=4, 0.8%). There were 380 patients who were diagnosed as SLN-negative and 122 (24.2%) were SLN-positive. A total of 85 SLN-positive patients received complete lymph node dissection, and 28 (32.9%) had additional positive lymph nodes. During a median follow-up of 24 months, 28 participants were found to have a false negative (FN) SLN. The FN rate was 18.7%. A higher T stage was a predictive factor for FN [odds ratio (OR) 1.77; P<0.05]. There was no significant difference in the positive or FN rate between the acral and cutaneous groups.ConclusionsThe radiopharmaceutical 99mTc-rituximab could be employed as a simple and safe tracer in acral and cutaneous melanoma SLN biopsies.

Ferroptosis-Associated Classifier and Indicator for Prognostic Prediction in Cutaneous Melanoma.

Ferroptosis plays a critical role in different types of cancers, but the prognostic impact of ferroptosis in cutaneous melanoma remains lacking. Therefore, ferroptosis-related genes (FRGs) were firstly obtained from the FerrDb database and the differentially expressed FRGs were identified by the “limma” algorithm. Next, the prognostic differentially expressed FRGs were screened out by univariate Cox regression, which were subsequently used to cluster melanomas into two subtypes (clusters A and B). Besides, the Boruta algorithm and principal component analysis (PCA) were performed to build a 15-FRGs indicator, which can robustly predict patients' overall survival (OS) and be considered as an independent prognostic factor in melanoma. The melanoma patients were further divided into high- and low-FRGs score groups. The high score group have a good prognosis, with higher T cell immune infiltrating and lower mutation frequencies in NRAS, KRAS, and NF1. Finally, we discovered that many immune processes and several chemotherapy drugs were closely associated with FRGs score. Thus, our study provides a novel ferroptosis-associated classifier and indicator to predict the prognosis of melanoma. Besides, we identified several potential chemotherapy drugs to induce ferroptosis and could supply additional effective treatments.

Volume tumor impact on melanoma survival assessed using Breslow density

Volume tumor impact on melanoma survival assessed using Breslow density

Evaluation of 2-methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma.

Experimental findings indicated that 2-methoxyestradiol (2-ME), an endogenous metabolite of 17β-estradiol, may exhibit anti-tumorigenic properties in various types of tumour, such as melanoma and endometrial carcinoma. In patients with endometrial cancer, the serum levels of 2-ME are decreased compared with those in healthy controls, and this finding has been associated with a poor outcome. The aim of the present study was to examine whether the serum levels of 2-ME are decreased in patients with melanoma, and whether this decrease may be correlated with disease stage and, therefore, serve as a prognostic indicator. ELISA was used to detect serum levels of 2-ME in patients with stage I-IV malignant melanoma (MM). A cohort of 78 patients with MM was analysed, along with 25 healthy controls, among whom 15 were women in the second trimester of pregnancy (positive control). As expected, significantly elevated levels of serum 2-ME were observed in pregnant control patients compared with those in patients with MM and healthy controls. There was no observed correlation between 2-ME serum levels in patients with MM and disease stage, tumour thickness, lactate dehydrogenase or S100 calcium-binding protein B levels. In addition, the 2-ME levels of patients with MM did not differ significantly from those of normal healthy controls. Overall, the findings of the present study indicated that the 2-ME serum levels in patients with MM were not decreased, and there was no correlation with early- or advanced-stage disease. Therefore, in contrast to published results on endometrial cancer, endogenous serum 2-ME levels in MM were not found to be correlated with tumour stage and did not appear to be a suitable prognostic factor in MM.

523 ANRIL inherited variants associated with primary melanoma TIL grade

Genome-wide association studies have reported an association between genetic variants in or near the ANRIL (CDKN2B-AS1) gene and age-related diseases. Despite these variants’ proximity to CDKN2A, which encodes melanoma tumor suppressor genes, their associations with melanoma prognostic factors are unknown. Here we investigated the associations of these variants with primary melanoma Breslow thickness, ulceration, and tumor-infiltrating lymphocyte (TIL) grade. Our analysis included 3,285 European-origin participants in the Genes, Environment and Melanoma (GEM) Study with incident invasive primary melanoma.