Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland

Dębniak, Tadeusz; Scott, Rodney J.; Lea, Rodney Arthur; Górski, Bohdan; Masojć, Bartłomiej; Cybulski, Cezary; Kram, Andrzej; Maleszka, Romuald; Gromowski, Tomasz; Paszkowska-Szczur, Katarzyna; Kashyap, Aniruddh; Lener, Marcin; Malińska, Karolina; Rogoża, Emilia; Murawa, Dawid; Rudnicka, Helena; Deptuła, Jakub; Lubiński, Jan

doi:10.4143/crt.2018.157

Cited by 9 publications

(3 citation statements)

References 21 publications

(20 reference statements)

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“…Te fourth biomarker is CREB3L3, a member of the basic leucine zipper family and the AMP-dependent transcription factor family. It can link to acute infammatory response and hepatocellular carcinoma [47]. Dewaele et al illustrated that EWSR1-CREB3L3 gene fusion is associated with a mesenteric sclerosing epithelioid fbrosarcoma [48].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer

Song

Wang

et al. 2023

Journal of Oncology

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Background. 5-methylcytosine (m5C) is a major site of RNA methylation modification, and its abnormal modification is associated with the development of gastric cancer (GC). This study aimed to explore the value of m5C-related genes on the prognosis of GC patients through bioinformatics. Methods. First, m5C-related genes were obtained by nonnegative matrix factorization (NMF) analysis and differentially expressed analysis. The m5C-related model was established and validated in distinct datasets. Moreover, a differential analysis of risk scores according to clinical characteristics was performed. The enrichment analysis was carried out to elucidate the underlying molecular mechanisms. Furthermore, we calculated the differences in immunotherapy and chemotherapy sensitivity between the high- and low-risk groups. Finally, we validated the expression levels of identified model genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results. A total of five m5C-related subtypes of GC patients in the TCGA database were identified. The m5C-related model was constructed based on APOD, ASCL2, MFAP2, and CREB3L3. Functional enrichment revealed that the m5C-related model might involve in the cell cycle and cell adhesion. Moreover, the high-risk group had a higher abundance of stromal and immune cells in malignant tumor tissues and a lower tumor purity than the low-risk group. The patients in the high-risk group were more sensitive to chemotherapy and had better sensitivity to CTLA4 inhibitors. Furthermore, qRT-PCR results from our specimens verified an over-expression of ASCL2, CREB3L3, and MFAP2 in the cancer cells compared with the normal cells. Conclusion. A total of five GC subtypes were identified, and a risk model was constructed based on m5C modification.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer

Song

Wang

et al. 2023

Journal of Oncology

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“…CABLES1 presented with only one highly ranked candidate and is generally not associated with UM or CM apart from containing a potential driver mutation site. 28 We obtained three topranked peptides from PMEL, another pigmentation gene and CM antigen, which is considered a highly ranked candidate biomarker in UM. 29 Finally, the gene OCA2 produced two top-ranked peptides for the allele A*02:01.…”

Section: Ranking Of Antigens Based On Their Importance In a Cancertar...mentioning

confidence: 99%

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy

Lischer,

Eberhardt,

Flamann

et al. 2024

J Immunother Cancer

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BackgroundTumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers.MethodsWe present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach. In addition to minimizing the risk of immune-related adverse events by selecting antigens based on their expression profile in tumor biopsies and healthy tissues, we incorporated a network analysis-derived antigen indispensability index based on computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model relying on peptide physicochemical characteristics.ResultsIn a model study of uveal melanoma, Human Leukocyte Antigen (HLA) docking simulations and experimental quantification of the peptide–major histocompatibility complex binding affinities confirmed that our approach discriminates between high-binding and low-binding affinity peptides with a performance similar to that of established methodologies. Blinded validation experiments with autologous T-cells yielded peptide stimulation-induced interferon-γ secretion and cytotoxic activity despite high interdonor variability. Dissecting the score contribution of the tested antigens revealed that peptides with the potential to induce cytotoxicity but unsuitable due to potential tissue damage or instability of expression were properly discarded by the computational pipeline.ConclusionsIn this study, we demonstrate the feasibility of the de novo computational selection of antigens with the capacity to induce an anti-tumor immune response and a predicted low risk of tissue damage. On translation to the clinic, our pipeline supports fast turn-around validation, for example, for adoptive T-cell transfer preparations, in both generalized and personalized antigen-directed immunotherapy settings.

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“…The expression of STK33 in pancreatic cancer, lung cancer, and liver cancer was signi cantly higher than that in corresponding non-cancerous tissues, indicating that the high expression of STK33 is closely related to the occurrence and development of pancreatic cancer, lung cancer and liver cancer (12)(13)(14). In the early stage of familial hereditary melanoma, the whole exon sequencing showed that STK33 was one of the 20 gene mutations, which suggested that STK33 played a role in its occurrence (15). Studies on lung cancer showed that the mRNA and protein expression of STK33 in lung adenocarcinoma, squamous cell carcinoma and small cell carcinoma were signi cantly higher than those in normal tissues, and the expression of STK33 in small cell carcinoma was higher than that in adenocarcinoma and squamous cell carcinoma (13,16).…”

Section: Introductionmentioning

confidence: 98%

STK33 Promotes the Proliferation and Metastasis of Human Esophageal Squamous Cell Carcinoma via Inflammation Related Pathway

Wang¹,

Huang

et al. 2022

Preprint

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The serine/threonine kinase STK33 has been implicated in cancer cell proliferation. Abnormal expression of STK33 is closely related to malignant tumors of many cancers. Here, we provide evidence of a critical role for STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression inhibited ESCC proliferation, migration, invasion, and tumor growth. Furthermore, STK33 was also involved in angiogenesis, TGFB, and inflammatory response in ESCC. Mechanistic investigations showed that STK33 regulated ESCC through multiple complex pathways. In showing that dysregulated STK33 signaling promotes ESCC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve ESCC treatment.

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Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland

Abstract: Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5 and STK33 with melanoma risk.

Cited by 9 publications

References 21 publications

Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer

Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy

STK33 Promotes the Proliferation and Metastasis of Human Esophageal Squamous Cell Carcinoma via Inflammation Related Pathway

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