Background: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers, causing about 72% of deaths in skin carcinoma. Although extensive study has explored the mechanism of recurrence and metastasis, the tumorigenesis of cutaneous melanoma remains unclear. Exploring the tumorigenesis mechanism may help identify prognostic biomarkers that could serve to guide cancer therapy. Method: Integrative bioinformatics analyses, including GEO database, TCGA database, DAVID, STRING, Metascape, GEPIA, cBioPortal, TRRUST, TIMER, TISIDB and DGIdb, were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of SKCM. Furthermore, immunohistochemistry (IHC) staining was performed to validate differential expression levels of hub genes between SKCM tissue and normal tissues from the First Affiliated Hospital of Soochow University cohort. Results: A total of 308 differentially expressed genes (DEGs) and 12 hub genes were found significantly differentially expressed between SKCM and normal skin tissues. Functional annotation indicated that inflammatory response, immune response was closely associated with SKCM tumorigenesis. KEGG pathways in hub genes include IL-10 signaling and chemokine receptors bind chemokine signaling. Five chemokines members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) were associated with better overall survival and pathological stages. IHC results suggested that significantly elevated CXCL9, CXCL10, CXCL13, CCL4 and CCL5 proteins expressed in the SKCM than in the normal tissues. Moreover, our findings suggested that IRF7, RELA, NFKB1, IRF3 and IRF1 are key transcription factors for CCL4, CCL5, CXCL10. In addition, the expressions of CXCL9, CXCL10, CXCL13, CCL4 and CCL5 were positively correlated with infiltration of six immune cells (B cell, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, dendritic cells) and 28 types of TILs. Among them, high levels of B cells, CD8 + T cells, neutrophils and dendritic cells were significantly related to longer SKCM survival time. Conclusion: In summary, this study mainly identified five chemokine members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) associated with SKCM tumorigenesis, progression, prognosis and immune infiltrations, which might help us evaluate several immune-related targets for cutaneous melanoma therapy.

Skin cutaneous melanoma (SKCM) is the deadliest cancer among commonly encountered skin malignant tumours due to its extreme aggressiveness and dissemination. 1 At present, SKCM is usually diagnosed in the late grades of metastatic tumours, which could drive patients to a poor response to the therapeutic strategies. 2 Therefore, we need to explore the potential biomarkers and therapeutic targets to improve the diagnosis and therapy of invasive melanoma. The malignant transformation of melanocytes is a multistep process. Melanocytes change their characteristics throughout the process, which enables them to proliferate and migrate. 2 Numerous methods such as assessing excised tumours, utilization of biomarkers and imaging techniques had been applied to detect and monitor

Lung cancer is the leading cause of cancer-related death. The majority of patients are diagnosed at an incurable advanced stage with poor prognosis. A recent study associated the methylation of homologous recombination genes with expression of immune checkpoints in lung squamous cell carcinoma. However, the correlation between them remains unclear. In our study, we propose that RAD51B, a repair gene in the homologous recombination process, which is noticed to be a key player in the maintenance of chromosome integrity and in sensing DNA damage, can act as an independent factor affecting the prognosis of non-small-cell lung cancer (NSCLC). Univariate analysis showed that overexpression of RAD51B is statistically significant correlated with better prognosis (P=0.013). Further, the multivariate Cox regression analysis showed that the morbidity of patients with high expression of RAD51B was decreased by 26% compared to those with low expression (HR=0.74, 95%CI: 0.59-0.93), especially for the patients with squamous cell carcinoma (HR=0.68, 95%CI: 0.51-0.90). In conclusion, RAD51B in mRNA level can be an important indicator to decide the prognosis of NSCLC and its overexpression predicts a preferable prognosis for NSCLC. Our results serve as a foundation for the investigation of the role of RAD51B in NSCLC, which may lead to potential therapeutic innovations.