Cancer Testis Antigen, NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer

Kim, Ye‐Rin; Kim, Ki-Uk; Lee, Jung‐Hee; Kim, Deok-Won; Chung, Joo-Seop; Kim, Yeong‐Dae; Shin, Dong‐Hoon; Lee, Min-Ki; Shin, Yong‐Il; Lee, Sang‐Yull

doi:10.3390/curroncol28030179

Cited by 11 publications

(4 citation statements)

References 36 publications

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“…Motylewska et al 49 examined the mRNA and protein levels of NEK2 in 22 cases of SCLC and found that elevated levels of NEK2 expression could be observed in patients with SCLC. Kim et al 50 revealed that NOL4 was expressed highly in SCLC and weakly or undetectably in non-SCLC, suggesting that NOL4 could act as a potential tumor antigen in SCLC. Güre et al 51 detected the expression of ZIC2 mRNA in 11 SCLC cell lines and normal tissues with PCR, and the result showed that ZIC2 was detected in 9 out of 11 SCLC cell lines.…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer

et al. 2023

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Background Immune checkpoint inhibitors (ICIs) have demonstrated promising outcomes in small cell lung cancer (SCLC), but not all patients benefit from it. Thus, developing precise treatments for SCLC is a particularly urgent need. In our study, we constructed a novel phenotype for SCLC based on immune signatures. Methods We clustered patients with SCLC hierarchically in 3 publicly available datasets according to the immune signatures. ESTIMATE and CIBERSORT algorithm were used to evaluate the components of the tumor microenvironment. Moreover, we identified potential mRNA vaccine antigens for patients with SCLC, and qRT-PCR were performed to detect the gene expression. Results We identified 2 SCLC subtypes and named Immunity High (Immunity_H) and Immunity Low (Immunity_L). Meanwhile, we obtained generally consistent results by analyzing different datasets, suggesting that this classification was reliable. Immunity_H contained the higher number of immune cells and a better prognosis compared to Immunity_L. Gene-set enrichment analysis revealed that several immune-related pathways such as cytokine-cytokine receptor interaction, programmed cell death-Ligand 1 expression and programmed cell death-1 checkpoint pathway in cancer were hyperactivated in the Immunity_H. However, most of the pathways enriched in the Immunity_L were not associated with immunity. Furthermore, we identified 5 potential mRNA vaccine antigens of SCLC (NEK2, NOL4, RALYL, SH3GL2, and ZIC2), and they were expressed higher in Immunity_L, it indicated that Immunity_L maybe more suitable for tumor vaccine development. Conclusions SCLC can be divided into Immunity_H and Immunity_L subtypes. Immunity_H may be more suitable for treatment with ICIs. NEK2, NOL4, RALYL, SH3GL2, and ZIC2 may be act as potential antigens for SCLC.

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Section: Discussionmentioning

confidence: 99%

Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer

et al. 2023

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“…CTA can be used as an immunotherapy target mediated by cytotoxicity T lymphocyte [23]. Some CTAs were identified to have immunogenicity, indicating the possibility of tumor immunotherapy targets [24][25][26]. In previous studies, compared with NY-ESO-1 (10.5%), which has been used in clinical immunotherapy, KK-LC-1 (32.6%) has a higher expression level in NSCLC [27].…”

Section: Discussionmentioning

confidence: 99%

Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma

et al. 2022

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Background Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated. Methods In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells. Results The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis. Conclusions In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.

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“…However, further investigations are necessitated to fully explore the effects of these genes on bone biology. The protein encoded by Nol4 is associated with RNA binding and has been identified as a cancer/testis antigen in humans, recently presented as a candidate target in small cell lung cancer ( Kim et al, 2021 ). However, the role of Nol4 in bone-related pathologies remains to be fully explored.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs

Toor

Wani

2021

Front. Genet.

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Osteoclasts are the sole bone resorbing cells, which undertake opposing roles to osteoblasts to affect skeletal mass and structure. However, unraveling the comprehensive molecular mechanisms behind osteoclast differentiation is necessitated to overcome limitations and scarcity of available data, particularly in relation with the emerging roles of long non-coding RNAs (LncRNAs) in gene expression. In this study, we performed comprehensive and progressive analyses of the dynamic transcriptomes of murine osteoclasts, generated in vitro. We compared the total RNA-based transcriptomes of murine bone marrow derived cells with differentiated osteoclasts, while focusing on potentially novel genes and LncRNAs, to uncover critical genes and their associated pathways, which are differentially regulated during osteoclast differentiation. We found 4,214 differentially regulated genes during osteoclast differentiation, which included various types of LncRNAs. Among the upregulated protein coding genes not previously associated with osteoclast are Pheta1, Hagh, Gfpt1 and Nol4, while downregulated genes included Plau, Ltf, Sell and Zfp831. Notably, we report Nol4 as a novel gene related to osteoclast activity since Nol4 knockout mice Nol4em1(International Mouse Phenotyping Consortium)J exhibit increased bone mineral density. Moreover, the differentially expressed LncRNAs included antisense and long intergenic non-coding RNAs, among others. Overall, immune-related and metabolism-related genes were downregulated, while anatomical morphogenesis and remodeling-related genes were upregulated in early-differentiated osteoclasts with sustained downregulation of immune-related genes in mature osteoclasts. The gene signatures and the comprehensive transcriptome of osteoclast differentiation provided herein can serve as an invaluable resource for deciphering gene dysregulation in osteoclast-related pathologic conditions.

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Cancer Testis Antigen, NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer

Cited by 11 publications

References 36 publications

Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer

Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer

Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma

Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs

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