Upregulated CD58 is associated with clinicopathological characteristics and poor prognosis of patients with pancreatic ductal adenocarcinoma

Zhang, Yalu; Liu, Qiaofei; Liu, Jing-Kai; Liao, Quan

doi:10.1186/s12935-021-02037-0

Cited by 9 publications

(11 citation statements)

References 57 publications

(60 reference statements)

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“…22 In vitro studies have shown that the deficiency of CD58 limits the recognition of tumor cells by T/NK cells, leading to immune evasion in a CD2/CD58-dependent manner. 23,24 Furthermore, our study highlighted the critical role of the tumor immune microenvironment in glioma progression and recurrence. Our findings from the TCGA database and our cohort demonstrated that CD2-CD58 axis expression levels are associated with WHO grades in LGG patients.…”

Section: Discussionmentioning

confidence: 73%

The CD2–CD58 axis: A novel marker predicting poor prognosis in patients with low‐grade gliomas and potential therapeutic approaches

Wu,

Chen,

Hua

et al. 2023

Immunity Inflam & Disease

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IntroductionLow‐grade gliomas (LGGs) are currently considered a premalignant condition for high‐grade gliomas (HGGs) and are characterized by a relatively intact immune system. Immunotherapeutic modalities may offer a safe and effective treatment option for these patients. However, the CD2–CD58 axis, an important component of the immunological synapse, remains unknown in LGG.MethodsRNA‐seq data from TCGA databases were analyzed. Immune cell infiltration was determined using a single‐sample gene set enrichment analysis (ssGSEA) based on integrated immune gene sets from published studies. Kaplan–Meier survival analysis, univariate and multivariate logistic analysis, and the ESTIMATE algorithm were employed to evaluate the impact of the CD2–CD58 axis on adult LGG patients.ResultsThe expression of the CD2–CD58 axis was found to be elevated with increasing of WHO grade (p < .05). Uni‐ and multi‐variable logistic analysis demonstrated that age, WHO grade, and CD58 levels were associated with poor prognosis in LGG patients with (p < .01). MetaSape pathways analysis revealed the involvement of CD58 in regulating T cell activation, leukocyte‐mediated immunity, and the positive regulation of cell activation in WHO grade II and III. CD58 expression correlated with infiltrations of CD4+ lymphocytes, NK cells, and macrophages cells. The ESTIMATE algorithm indicated that patients with high CD58 expression had significantly higher immune scores compared with low CD58 expression in WHO grade II/III, but no statistical difference was observed in WHO grade IV (p < .05). Furthermore, correlation analysis demonstrated the significant association between CD58 and CD274 (r = 0.581, p < .001), HAVCR2 (r = 0.58i7, p < .001), and LGALS9 (r = 0.566, p < .001). Immunohistochemical staining further confirmed the relationship of CD58, HAVCR2, WHO grade, and prognosis in grade II and III patients.ConclusionOverall, our findings highlight the significant association between the CD2–CD58 axis and poor survival in LGG patients. High CD58 expression is implicated in T cell‐mediated immune responses as an immunosuppressive factor and affect inhibitory immune checkpoint genes.

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Section: Discussionmentioning

confidence: 73%

The CD2–CD58 axis: A novel marker predicting poor prognosis in patients with low‐grade gliomas and potential therapeutic approaches

Wu,

Chen,

Hua

et al. 2023

Immunity Inflam & Disease

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“…Similarly, CHRDL1 is shown to be associated with good prognostic outcomes 15,32 . Increased levels of SPA17 and CD58 were previously linked to poor prognostic outcome in breast and pancreatic cancer patients, respectively 33,34 . Similarly, higher levels of MTBP are also associated with poor prognostic outcomes in various cancer types 35–37 .…”

Section: Discussionmentioning

confidence: 95%

Gene expression profiling of pancreatic ductal adenocarcinomas in response to neoadjuvant chemotherapy

et al. 2023

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AimPancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Chemotherapy is the mainstay systemic therapy for PDAC, and chemoresistance is a major clinical problem leading to therapeutic failure. This study aimed to identify key differences in gene expression profile in tumors from chemoresponsive and chemoresistant patients.MethodsArchived formalin‐fixed paraffin‐embedded tumor tissue samples from patients treated with neoadjuvant chemotherapy were obtained during surgical resection. Specimens were macrodissected and gene expression analysis was performed. Multi‐ and univariate statistical analysis was performed to identify differential gene expression profile of tumors from good (0%–30% residual viable tumor [RVT]) and poor (>30% RVT) chemotherapy‐responders.ResultsInitially, unsupervised multivariate modeling was performed by principal component analysis, which demonstrated a distinct gene expression profile between good‐ and poor‐chemotherapy responders. There were 396 genes that were significantly (p < 0.05) downregulated (200 genes) or upregulated (196 genes) in tumors from good responders compared to poor responders. Further supervised multivariate analysis of significant genes by partial least square (PLS) demonstrated a highly distinct gene expression profile between good‐ and poor responders. A gene biomarker of panel (IL18, SPA17, CD58, PTTG1, MTBP, ABL1, SFRP1, CHRDL1, IGF1, and CFD) was selected based on PLS model, and univariate regression analysis of individual genes was performed. The identified biomarker panel demonstrated a very high ability to diagnose good‐responding PDAC patients (AUROC: 0.977, sensitivity: 82.4%; specificity: 87.0%).ConclusionA distinct tumor biological profile between PDAC patients who either respond or not respond to chemotherapy was identified.

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“…Several reports have shown that both EMT and cancer stem cell markers are expressed in PC [ 33 ] [ 34 ]. It has been reported that LGR5 and EMT-related transcription factors are co-expressed in intrahepatic cholangiocarcinoma [ 35 ], but re-verification of their LGR5 expression data by immunohistochemistry and re-verification RNA in situ is desired.…”

Section: Discussionmentioning

confidence: 99%

LGR5 expression and clinicopathological features of the invasive front in the fat infiltration area of pancreatic cancer

et al. 2022

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Background Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a strong cancer stem cell marker in colorectal cancer; however, there are many unclear aspects of LGR5 expression in pancreatic cancer. It has been reported that the interaction between tumor cells and stroma at the fat infiltration site has a significant effect on pancreatic cancer prognosis. Therefore, we report a clinicopathological study of LGR5 expression at the fat invasion front in pancreatic cancer. Methods LGR5 expression was analyzed in 40 pancreatic ductal adenocarcinoma cases with RNAscope, which is a newly developed high-sensitivity in situ hybridization method. Epithelial-mesenchymal transition (EMT) was analyzed by the expression of E-cadherin and vimentin via immunohistochemistry. Results LGR5-positive dots were identified in all cases, especially with glandular formation. In the fat invasion front, a high histological grade showed significantly reduced LGR5 expression compared with a low histological grade (p=0.0126). LGR5 expression was significantly higher in the non-EMT phenotype group than in EMT phenotype group (p=0.0003). Additionally, LGR5 expression was significantly lower in cases with high vascular invasion than in those with low vascular invasion (p=0.0244). Conclusions These findings suggest that decreased LGR5 expression in the fat invasion front is associated with more aggressive biological behavior in pancreatic ductal adenocarcinoma, with higher tumor grade, EMT phenotype, and higher vascular invasion.

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Upregulated CD58 is associated with clinicopathological characteristics and poor prognosis of patients with pancreatic ductal adenocarcinoma

Cited by 9 publications

References 57 publications

The CD2–CD58 axis: A novel marker predicting poor prognosis in patients with low‐grade gliomas and potential therapeutic approaches

The CD2–CD58 axis: A novel marker predicting poor prognosis in patients with low‐grade gliomas and potential therapeutic approaches

Gene expression profiling of pancreatic ductal adenocarcinomas in response to neoadjuvant chemotherapy

LGR5 expression and clinicopathological features of the invasive front in the fat infiltration area of pancreatic cancer

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