Tumour- associated autoantibodies as prognostic cancer biomarkers- a review

Sexauer, Désirée; Gray, Elin S.; Zaenker, Pauline

doi:10.1016/j.autrev.2022.103041

Cited by 32 publications

(19 citation statements)

References 108 publications

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“…2g ), presumably mediating aberrant tumor immunity and promoting tumor aggressiveness (Fig. 2h ) 21 . Putative mEPCs in CC1 strikingly showed the highest expression of PLA2G2A (log 2 FC = 3.72, P = 7.5 × 10 −13 ) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

et al. 2022

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Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A+ epithelial cells with copy number variation were identified from a histologically benign sample. We validated significant overexpression of PLA2G2A across in situ GBCs, together with increased proliferation and cancer stemness in PLA2G2A-overexpressing GBC cells, indicating an important role for PLA2G2A during early carcinogenesis. Malignant epithelial cells displayed pervasive cancer hallmarks and cellular plasticity, differentiating into metaplastic, inflammatory, and mesenchymal subtypes with distinct transcriptomic, genomic, and prognostic patterns. Chronic cholecystitis led to an adapted microenvironment characterized by MDSC-like macrophages, CD8+ TRM cells, and CCL2+ immunity-regulating fibroblasts. By contrast, GBC instigated an aggressive and immunosuppressive microenvironment, featured by tumor-associated macrophages, Treg cells, CD8+ TEX cells, and STMN1+ tumor-promoting fibroblasts. Single-cell and bulk RNA-seq profiles consistently showed a more suppressive immune milieu for GBCs with inflammatory epithelial signatures, coupled with strengthened epithelial-immune crosstalk. We further pinpointed a subset of senescence-like fibroblasts (FN1+TGM2+) preferentially enriched in metastatic lesions, which promoted GBC migration and invasion via their secretory phenotype. Collectively, this study provides comprehensive insights into epithelial and microenvironmental reprogramming throughout cholecystitis-propelled carcinogenesis and metastasis, laying a new foundation for the precision therapy of GBC.

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Section: Resultsmentioning

confidence: 99%

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

et al. 2022

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“…Meanwhile, KM analyses showed that COAD patients with high CD276 expression had relatively poor OS, DSS and PFI (all P < 0.05). So far, signi cant heterogeneity in prognostic factors has been considered among individuals with COAD and the existing clinical prognostic predictors are not precise enough [26,27], it is extremely necessary to establish a genomic-clinicopathologic nomogram to predict the long-term outcomes of patients with advanced colorectal cancer. We created nomograms models with the independent prognostic parameters (including CD276 expression and residual_tumor) for OS and DSS of patients.The results showed that the genomic-clinicopathologic nomograms represented more precise prognostic models compared with the other clinical predictors alone.…”

Section: Discussionmentioning

confidence: 99%

The bioinformatics and experimental analysis of CD276 for prognosis and immune infiltrates in colon adenocarcinoma

Chen

Chai

et al. 2022

Preprint

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BackgroundColon adenocarcinoma (COAD), although the third-most common type of gastrointestinal tumors, still lacks specific biomarkers for early diagnosis, treatment, and prognosis. CD276, an immune checkpoint, is upregulated in various cancers.This study aimed to evaluate the role of CD276 in tumorigenesis, prognosis and immunity for COAD.MethodsThe expression profile of CD276 gene in COAD was established by using RNA-sequencing transcriptomic data of The Cancer Genome Atlas (TCGA) databases. The biological functions of CD276 were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between CD276 and immune cell infiltration was investigated by TIMER website. Correlation analysis was performed between CD276 expression and clinicopathological characteristics. Cox proportional hazard regression and Kaplan-Meier final analysis were applied for identifying the prognostic role of CD276. ResultsCD276 expression was significantly elevated in COAD tumor (P < 0.0001). Functional annotation revealed many enriched GO-terms among which the activity of the growth factor, cell adhesion and corresponding cancer-related pathways were highly represented in high CD276 expression phenotype. High CD276 was associated with microsatellite instability (MSI) status, patients’ survival, and disease progression. Cox regression analysis revealed that CD276 was a risk factor for overall survival [hazard ratio (HR): 1.848, P = 2.64E−03], disease-specific survival (HR: 2.406, P = 5.35E−04), and progression-free interval (HR: 1.772, P = 2.04E−03). Moreover, CD276 level was significantly associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression.ConclusionsOur analyses indicated that increased CD276 may contribute to COAD development by activing tumor‐promoting signal pathways and altering the immune microenvironment. It is believed that abnormal expression of CD276 has clinical prognostic value in COAD patients.

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“…Humoral immune responses toward TAAs result in production of tumor-associated autoantibodies (AAbs) which are less subject to proteolysis and highly stable in serum compared to soluble TAAs. As a result, tumor-associated AAbs can persist at lasting levels in serum even when corresponding TAAs are no longer detectable, and have been proposed as serum biomarkers for predicting cancer outcomes and patients’ survival in various types of human cancer [ 12 , 13 ]. Despite the clinical potential of AAb, the prognostic value of utilizing single AAb could be limited due to tumor heterogeneity [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the clinical potential of AAb, the prognostic value of utilizing single AAb could be limited due to tumor heterogeneity [ 14 ]. In this regard, it has brought increased attention to identifying a tailored panel of tumor-associated AAbs for better prognostic prediction [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors

Yuan

Chang

Chou

et al. 2022

Animals

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Canine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes. We have identified CMT-associated autoantibodies against thymidylate synthetase (TYMS), insulin-like growth factor-binding protein 5 (IGFBP5), hyaluronan and proteoglycan link protein 1 (HAPLN1), and anterior gradient 2 (AGR2), i.e., TYMS-AAb, IGFBP5-AAb, HAPLN1-AAb, and AGR2-AAb, respectively, by conducting serological enzyme-linked immunosorbent assays (ELISA). Herein we assessed serum AAb levels in 11 MMT dogs before and after surgery, demonstrating that IGFBP5-AAb and HAPLN1-AAb significantly decrease at 3- and 12-months post-surgery (p < 0.05). We evaluated the correlation between the presurgical AAb level and overall survival (OS) of 90 CMT dogs after surgery. Kaplan-Meier survival analysis reveals that IGFBP5-AAbHIgh and TYMS-AAbHigh are significantly correlated with worse OS (p = 0.017 and p = 0.029, respectively), while AGR2-AAbLow is correlated with somewhat poorer OS (p = 0.086). Areas under a time-dependent receiver operating characteristic curve (AUC) of IGFBP5-AAb and TYMS-AAb in predicting OS of MMT dogs are 0.611 and 0.616, respectively. Notably, MMT dogs presenting TYMS-AAbHigh/IGFBP5-AAbHigh/AGR2-AAbLow have worst OS (p = 0.0004). This study reveals an association between the serum AAb level and CMT prognosis.

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Tumour- associated autoantibodies as prognostic cancer biomarkers- a review

Cited by 32 publications

References 108 publications

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

The bioinformatics and experimental analysis of CD276 for prognosis and immune infiltrates in colon adenocarcinoma

The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors

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