Search

Purpose:Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease.Experimental Design:A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets.Results:Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10−8 to 10−4) but showed a significant interaction with AJCC stage (P = 0.04) and did not predict outcome in stage I tumors (P = 0.3–0.7). Consensus-based classification of the LMC dataset identified six classes that predicted outcome, notably in stage I disease. LMC class was a similar indicator of prognosis when compared with SNB, and it added prognostic value to the genes reported by Gerami and colleagues. One particular LMC class consistently predicted poor outcome in patients receiving immunotherapy in two of three tested datasets. Biological characterization of this class revealed high JUN and AXL expression and evidence of epithelial-to-mesenchymal transition.Conclusions:A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy.

Supplementary Figures and tables

Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease. Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets. Results: Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10−8 to 10−4) but showed a significant interaction with AJCC stage (P = 0.04) and did not predict outcome in stage I tumors (P = 0.3–0.7). Consensus-based classification of the LMC dataset identified six classes that predicted outcome, notably in stage I disease. LMC class was a similar indicator of prognosis when compared with SNB, and it added prognostic value to the genes reported by Gerami and colleagues. One particular LMC class consistently predicted poor outcome in patients receiving immunotherapy in two of three tested datasets. Biological characterization of this class revealed high JUN and AXL expression and evidence of epithelial-to-mesenchymal transition. Conclusions: A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy.

Skin lesion border irregularity, which represents the B feature in the ABCD rule, is considered one of the most significant factors in melanoma diagnosis. Since signs that clinicians rely on in melanoma diagnosis involve subjective judgment including visual signs such as border irregularity, this deems it necessary to develop an objective approach to finding border irregularity. Increased research in neural networks has been carried out in recent years mainly driven by the advances of deep learning. Artificial neural networks (ANNs) or multilayer perceptrons have been shown to perform well in supervised learning tasks. However, such networks usually don't incorporate information pertaining the ambiguity of the inputs when training the network, which in turn could affect how the weights are being updated in the learning process and eventually degrading the performance of the network when applied on test data. In this paper, we propose a fuzzy multilayer perceptron (F-MLP) that takes the ambiguity of the inputs into consideration and subsequently reduces the effects of ambiguous inputs on the learning process. A new optimization function, the fuzzy gradient descent, has been proposed to reflect those changes. Moreover, a type-II fuzzy sigmoid activation function has also been proposed which enables finding the range of performance the fuzzy neural network is able to attain. The fuzzy neural network was used to predict the skin lesion border irregularity, where the lesion was firstly segmented from the skin, the lesion border extracted, border irregularity measured using a proposed measure vector, and using the extracted border irregularity measures to train the neural network. The proposed approach outperformed most of the state-of-the-art classification methods in general and its standard neural network counterpart in particular. However, the proposed fuzzy neural network was more time-consuming when training the network.

Lesion border detection is considered a crucial step in diagnosing skin cancer. However, performing such a task automatically is challenging due to the low contrast between the surrounding skin and lesion, ambiguous lesion borders, and the presence of artifacts such as hair. In this paper we propose a two-stage approach for skin lesion border detection: (i) segmenting the skin lesion dermoscopy image using U-Net, and (ii) extracting the edges from the segmented image using a novel approach we call FuzzEdge. The proposed approach is compared with another published skin lesion border detection approach, and the results show that our approach performs better in detecting the main borders of the lesion and is more robust to artifacts that might be present in the image. The approach is also compared with the manual border drawings of a dermatologist, resulting in an average Dice similarity of 87.7%.

Background The incidence of melanoma is rising. Early detection is associated with a more favourable outcome. The factors that influence the timing of a patient’s presentation for medical assessment are not fully understood. The aims of the study were to measure the nature and duration of melanoma symptoms in a group of patients diagnosed with melanoma within the preceding 18 months and to identify the symptoms and barriers associated with a delay in presentation. Methods A questionnaire was distributed to a random sample of 200 of the 963 melanoma patients who had participated in the Cancer Patient Experience Survey 2010 and were known to be alive 1 year later. Data were collected on symptoms, duration of symptoms prior to presentation and the reasons for not attending a doctor sooner. Results A total of 159 patients responded to the questionnaire; 74 (47%) were men; mean age was 62 (range 24–90) years. Of the 149 patients who reported a symptom, 40 (27%) had a delayed presentation (i.e. >3 months). A mole growing bigger was the most common symptom and reporting this symptom was significantly associated with a delayed presentation (odds ratio (OR) 2.04, 95% confidence interval (95% CI) 1.14–5.08). Patients aged ≥65 years were less likely to report a barrier to presentation and were less likely to delay than those under 40, although this was of borderline statistical significance (OR 0.28, 95% CI 0.08–1.00). Conclusions This study highlights that an enlarging mole is a significant symptom influencing the timing of presentation. Increasing public awareness of the signs of melanoma and of the importance of early presentation is desirable. Health professionals should take advantage of the opportunity to educate patients on such symptoms and signs where feasible. Further exploration of the barriers to presentation in younger people should be considered. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2978-6) contains supplementary material, which is available to authorized users.