Acral melanoma detection using dermoscopic images and convolutional neural networks

Acral melanoma (AM) is a rare and lethal type of skin cancer. It can be diagnosed by expert dermatologists, using dermoscopic imaging. It is challenging for dermatologists to diagnose melanoma because of the very minor differences between melanoma and non-melanoma cancers. Most of the research on skin cancer diagnosis is related to the binary classification of lesions into melanoma and non-melanoma. However, to date, limited research has been conducted on the classification of melanoma subtypes. The current study investigated the effectiveness of dermoscopy and deep learning in classifying melanoma subtypes, such as, AM. In this study, we present a novel deep learning model, developed to classify skin cancer. We utilized a dermoscopic image dataset from the Yonsei University Health System South Korea for the classification of skin lesions. Various image processing and data augmentation techniques have been applied to develop a robust automated system for AM detection. Our custom-built model is a seven-layered deep convolutional network that was trained from scratch. Additionally, transfer learning was utilized to compare the performance of our model, where AlexNet and ResNet-18 were modified, fine-tuned, and trained on the same dataset. We achieved improved results from our proposed model with an accuracy of more than 90 % for AM and benign nevus, respectively. Additionally, using the transfer learning approach, we achieved an average accuracy of nearly 97 %, which is comparable to that of state-of-the-art methods. From our analysis and results, we found that our model performed well and was able to effectively classify skin cancer. Our results show that the proposed system can be used by dermatologists in the clinical decision-making process for the early diagnosis of AM.

Integrative Molecular and Clinical Profiling of Acral Melanoma Identifies LZTR1 as a Key Tumor Promoter and Therapeutic Target

Acral melanoma, the most common melanoma subtype among non-Caucasian individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we performed integrative genomic and clinical profiling of acral melanomas from a cohort of 104 patients treated in North America or China. We found that recurrent, late-arising amplifications of cytoband chr22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 – a known tumor suppressor in other cancers – is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines caused apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiated processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and increased levels of MAPK and SRC activities. Our results provide new insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target

Mapping of single-cell landscape of acral melanoma and analysis of molecular regulatory network of tumor microenvironment

Melanoma is a type of skin malignant tumor with high invasiveness, high metastasis, and poor prognosis. The incidence of melanoma continues to increase. Among them, the subtype of acral melanoma (AM) is more common in Asian populations. AM has higher degree, low immunotherapy response rate. With the help of single-cell sequencing technology provides new technical means for tumor microenvironment research, so that we can more easily explore specific tumor types suitable immunotherapy targets. However, no complete single-cell level differentiation map exists for the AM tumor microenvironment (TME). In this study, we used AM related sample and used the 10x Genomics single-cell transcriptome platform to draw a specific single-cell map of AM, understand the cell composition of AM, and analyze the interaction and molecular regulation of AM TME. Nine cell types were identified, of which malignant cells accounted for the largest proportion, followed by fibroblasts. And the cell interaction network shows that malignant cells, macrophages, B cells, T cells and fibroblasts play important roles in AM TME. Our research provides systematic theoretical guidance for the diagnosis and treatment of acral melanoma.

Overall Survival of Patients With Unresectable or Metastatic BRAF V600-Mutant Acral/Cutaneous Melanoma Administered Dabrafenib Plus Trametinib: Long-Term Follow-Up of a Multicenter, Single-Arm Phase IIa Trial

ObjectivesTo examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness.MethodsThis was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed.ResultsA total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 individuals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5–82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites<3 and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS.ConclusionDabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02083354, identifier NCT02083354.