Granzyme family acts as a predict biomarker in cutaneous melanoma and indicates more benefit from anti-PD-1 immunotherapy

Wu, Xia; Wang, Xiaojie; Zhao, Yan; Li, Kun; Yu, Bo; Zhang, Jianzhong

doi:10.7150/ijms.54747

Cited by 18 publications

(23 citation statements)

References 39 publications

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“…Among the genes downregulated in the POD24 group, GZMM and GZMK , which are commonly expressed in CTLs and NK cells, have pro‐apoptotic activities on tumor cells 45 . A low expression of GZMM and GZMK in tumor tissues has been associated with an unfavorable prognosis in cutaneous melanoma, 46 and GZMK was also found to be downregulated in the process of FL transformation 47 . Together, these results suggested that anti‐FL immune responses may be weakened in RB‐treated FL patients undergoing POD24.…”

Section: Discussionmentioning

confidence: 98%

Decreased expression of T‐cell‐associated immune markers predicts poor prognosis in patients with follicular lymphoma

et al. 2021

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We previously examined the utility of rituximab‐bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R‐CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB‐treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression‐free survival (PFS) in the RB‐treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8+ T‐cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24‐mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB‐treated patients into immune IIShigh (n = 19) and IISlow (n = 20) groups. The 3‐y PFS rate was significantly lower in the IISlow group than in the IIShigh group (50.0% [95% CI: 27.1‐69.2%] vs. 84.2% [95% CI: 58.7‐94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T‐cell‐associated immune markers could be useful to predict prognosis in RB‐treated FL patients. (UMIN:000 013 795, jRCT:051 180 181)

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Section: Discussionmentioning

confidence: 98%

Decreased expression of T‐cell‐associated immune markers predicts poor prognosis in patients with follicular lymphoma

et al. 2021

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“…Granzymes are a family of homologous serine proteases that can induce apoptosis in various tumor cells (Anthony et al, 2010). Granzymes also encode the genes of some virtual granzymes and components of immunocytes, that are part of the cancer immune microenvironment (Wu et al, 2021). Among human granzymes, GZMA is also pivotal for the activation of immunocytes in tumors (Romero et al, 2020;Rooney et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma

Chen

Jin

et al. 2021

PeerJ

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Background Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear. Methods Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database. Results Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.

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“…We explore the potential tumorigenesis mechanism of IFN-γ with TIME. The former scholars were investigated about anti-PD-1 resistance and occurrence of melanoma [51][52][53]. Hänze J, et al showed that high PD-L1-mRNA levels in tumor tissues with a positive IFN-γ signature favorably affect OS [41,54,55].…”

Section: Discussionmentioning

confidence: 99%

Synthesize Analysis of the IFN-γ and Immune Infiltrates of m6A RNA Methylation Regulators in Human Skin Cutaneous Melanoma

Wang

Huang

et al. 2021

Preprint

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Background: SKCM is a major common cancer with highly mortality and morbidity, causing about 72% of deaths in skin carcinoma. In recent years, more scholars have selected one or two m6A regulatory factors to explore the abnormal expression and potential mechanism of m6A in tumorigenesis and development. So as to find the relevant biomarkers in the whole tumorigenesis process.Methods: In current study, we used public transcriptome datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) to investigate the relationships between N6-methyl adenosine(m6A) regulators genes and Skin cutaneous melanoma (SKCM). Then, SKCM patients were grouped based on the cluster analysis of m6A regulators expression. Compared the relationship between Interferon (IFN)-γ and immune infiltrates. Results: Based on the survival curves of subgroups, we selected 20 potential predictive m6A-related genes were overexpressed in SKCM. And based on the typing results, we got the 15 differential expression genes between the three groups. Four of them (CYP2U1, SEMA6A, GRIA2, and TSPAN13) were selected in Cox regression, which were significant expression in overall survival(p<0.05). Interferon (IFN)-γ is a central cytokine, which effecting immune-provoking and recognizing transformed cells in anti-tumour immunity. Conclusions: To investigate the correlation between IFN-γ and SKCM. We have identified that IFN-γ is a potential factor for cancer therapy, and affecting expression pathways of SKCM. Among them, IFN-γ and WTAP were the most positive correlation. These sights suggest that IFN-γ can potentially be utilized for immune pathway such as melanoma skin cancer.

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Granzyme family acts as a predict biomarker in cutaneous melanoma and indicates more benefit from anti-PD-1 immunotherapy

Cited by 18 publications

References 39 publications

Decreased expression of T‐cell‐associated immune markers predicts poor prognosis in patients with follicular lymphoma

Decreased expression of T‐cell‐associated immune markers predicts poor prognosis in patients with follicular lymphoma

A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma

Synthesize Analysis of the IFN-γ and Immune Infiltrates of m6A RNA Methylation Regulators in Human Skin Cutaneous Melanoma

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