A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers

Chen, Yihong; Liu, Yin; Han, Ying; Tan, Jun; Guo, Chunmei; Cai, Changjing; Liu, Ping; Peng, Yinghui; Liu, Yihan; Wang, Xinwen; Zeng, Shan; Feng, Ziyang; Shen, Hong

doi:10.1186/s12575-023-00201-6

Cited by 5 publications

(1 citation statement)

References 54 publications

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“…It plays a crucial role in the S phase and G2/M phase of the cell cycle, regulating DNA replication and cell division [18,21,22]. Furthermore, elevated expression of CLSPN is closely related to the induction of immune cell infiltration, tumor mutation burden, microsatellite instability, mismatch repair, and DNA methylation in various cancer types [23]. In recent years, researchers have begun to study the role of the CLSPN gene in cancer development, specifically after finding high levels of CLSPN in cancers as diverse as breast, ovarian, cervical, glioma, non-small cell lung cancer and renal cell carcinoma [24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression

Hsieh,

Lo,

et al. 2024

IJMS

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Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of variants associated with the most common alleles. Cancer occurrence and progression are significantly affected by Claspin (CLSPN) gene polymorphism present in the population, which alters the expression, function, and regulation of the gene. CLSPN genotypes are associated with oral cancer, but the literature on this association is limited. As a result, the goal of this study is to investigate the correlation between CLSPN genotypes and oral cancers’ development. This study will explore the presence of four CLSPN SNPs including rs12058760, rs16822339, rs535638 and rs7520495 gene polymorphisms, and analyze the expression of these genes in 304 cancer-free controls and 402 oral squamous cell carcinoma (OSCC) cases. Attempts have been made to obtain insight into the role of CLSPN gene polymorphisms in oral cancer through the analysis of this study. We demonstrated that the OSCC risk of individuals with four CLSPN SNPs relative to the wild type did not differ significantly from that of the wild type when the polymorphisms are analyzed according to individual habits. We further studied the mechanism by which CLSPN polymorphisms affect the progression of clinicopathological features in OSCC patients. The results of the degree of cell differentiation showed that compared with patients of rs7520495 SNP carrying the CC genotype, the incidence of poor cell differentiation in patients carrying the CC + GG genotype was higher (AOR: 1.998-fold; 95% CI, 1.127–3.545; p = 0.018). In particular, patients with the G genotype of rs7520495 had increased poor cell differentiation compared with patients with the C genotype (AOR: 4.736-fold; 95% CI, 1.306–17.178; p = 0.018), especially in the drinking group. On the basis of our analysis of the Cancer Genome Atlas dataset, we found that higher CLSPN levels were associated with poorer cell differentiation in oral cancers. In this study, we provide the first evidence showing that CLSPN SNPs contribute to oral cancer. Whether or not rs7520495 can be used as a confirmatory factor in the future is uncertain, but it seems likely that it can be used as an important factor in predicting recurrence, response to treatment and medication toxicity to patients with oral cancer.

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Section: Introductionmentioning

confidence: 99%

The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression

Hsieh,

Lo,

et al. 2024

IJMS

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Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimization

Hori,

Yamada,

Murata

et al. 2024

Human Vaccines & Immunotherapeutics

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Adoptive T cell therapy, using T cell receptor-engineered T (TCR-T) cells and chimeric antigen receptor T (CAR-T) cells, is a potent immunotherapy option. Bladder cancer is a prevalent urological malignancy, particularly in cases of muscle invasion and metastasis, for which systemic therapy is crucial. Immunotherapy utilizing immune checkpoint blockade has been approved for bladder cancer treatment. The antitumor effect of an immune checkpoint blockade based on cytotoxic T cells (CTLs) and the patient’s immune status is essential. The chemotherapeutic drug cisplatin (CDDP) is a key drug in bladder cancer treatment. However, it has been shown to suppress T cells, making combination therapy with CDDP and immunotherapy difficult. To address this, we developed TCR-T cells specific for bladder cancer cells. In previous studies, we found that the tumor-associated antigen CLSPN is overexpressed in CDDP-resistant bladder cancer cells and that the antigenic peptide HLA-A*02:01/CLSPN 1254–1262 , encoded by CLSPN, could be targeted by a CTL clone. The TCR was cloned from the HLA-A*02:01/CLSPN 1254–1262 specific CTL clone yc3. We also designed a codon-optimized TCR sequence using GeneArt® GeneOptimizer® (Opt TCR) and compared the TCR-T cells using the original TCR sequence (Ori TCR-T cells) and the codon-optimized TCR sequence (Opt TCR-T cells). Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN 1254–1262 specific Opt TCR-T cells are promising candidates for CDDP combination therapy.

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mcRigor: a statistical method to enhance the rigor of metacell partitioning in single-cell data analysis

Liu,

2024

Preprint

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In single-cell data analysis, addressing sparsity often involves aggregating the profiles of homogeneous single cells into metacells. However, existing metacell partitioning methods lack checks on the homogeneity assumption and may aggregate heterogeneous single cells, potentially biasing down- stream analysis and leading to spurious discoveries. To fill this gap, we introduce mcRigor, a statistical method to detect dubious metacells, which are composed of heterogeneous single cells, and optimize the hyperparameter of a metacell partitioning method. The core of mcRigor is a feature-correlation-based statistic that measures the heterogeneity of a metacell, with its null distribution derived from a double permutation mechanism. As an optimizer for existing metacell partitioning methods, mcRigor has been shown to improve the reliability of discoveries in single-cell RNA-seq and multiome (RNA+ATAC) data analyses, such as uncovering differential gene co-expression modules, enhancer-gene associations, and gene temporal expression. Moreover, mcRigor enables benchmarking and selection of the most suitable metacell partitioning method with optimized hyperparameters tailored to specific datasets, ensuring re- liable downstream analysis. Our results showed that MetaCell and SEACells consistently outperformed MetaCell2 and SuperCell, though their superior performance comes at the expense of longer runtimes.

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A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers

Cited by 5 publications

References 54 publications

The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression

The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression

Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimization

mcRigor: a statistical method to enhance the rigor of metacell partitioning in single-cell data analysis

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