Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers

Høgdall, Dan; O’Rourke, Colm J.; Dehlendorff, Christian; Larsen, Olav; Jensen, Lars Henrik; Johansen, Astrid Z.; Dang, Hien; Factor, Valentina M.; Grunnet, Mie; Oliveira, Douglas V.N.P.; Linnemann, Dorte; Boisen, Mogens K.; Wang, Xin Wei; Johansen, Julia S.; Andersen, Jesper B.

doi:10.1158/1078-0432.ccr-19-2700

Cited by 24 publications

(31 citation statements)

References 54 publications

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“…Among the current treatment regimens, the antiangiogenic bevacizumab may hold promise for the IL6-expressing stress-high tumors, as increased plasma levels of IL6 are indicative of bevacizumab sensitivity in HGSOC (47). Furthermore, antibodies against IL6, TNF, LIF, CXCL12, or their receptors, some of which are already in clinical use to treat inflammatory diseases, have shown initially promising results in preclinical models when combined with platinum chemotherapy (49)(50)(51)(52). In addition, the regulators up-and downstream of IL6, namely, STAT3 and Toll-like receptors, respectively, have been successfully targeted in resistant cancer models (53,54).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

et al. 2022

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Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their transcriptomic profiles at a single-cell resolution. After removing patient-specific signals by a novel analysis approach, PRIMUS, we found a consistent increase in stress-associated cell state during chemotherapy, which was validated by RNA in situ hybridization and bulk RNA sequencing. The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival. Co-occurrence with an inflammatory cancer–associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop. In summary, we have found a resistant state that integrates stromal signaling and subclonal evolution and offers targets to overcome chemotherapy resistance.

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Section: Discussionmentioning

confidence: 99%

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

et al. 2022

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“…At present, a large number of studies have confirmed that IL6R is related to tumors (15)(16)(17)(18). Studies have even shown that IL6 could be used as a prognostic biomarker for cholangiocarcinoma, and IL6R could be used as a therapeutic target for cholangiocarcinoma (38). However, there are few studies on IL6R in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Low expression of IL6R predicts poor prognosis for lung adenocarcinoma

Sun¹,

Wang²,

Shi³

et al. 2021

Ann Transl Med

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Background: Interleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD).Methods: In this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).Results: Through the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients. Conclusions:In summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.

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“… 20 , 21 Inflammation mediators are the hallmark of several risk factors associated with ICC. 22 We included several inflammation-based scores and analyzed their prognostic efficacy in this large, multicentre cohort study. It was shown that mGPS was identified as the significant prognostic factor for OS and PFS, independent of CA19-9 value and TNM stage.…”

Section: Discussionmentioning

confidence: 99%

An Inflammation-Index Signature Predicts Prognosis of Patients with Intrahepatic Cholangiocarcinoma After Curative Resection

Zhao

Chen

et al. 2021

JIR

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Background:The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) after resection is at great variance. We aimed to establish a novel prognostic nomogram in facilitating the risk stratification for these patients. Methods: A total of 82 high-dimensional radiological and pathological data were analyzed by LASSO-penalized Cox regression analyses and the panels with the best predictive performance were selected. Specific nomograms were established based on the selected panels and were validated in both primary (n=292) and validation cohorts (n=107). The area under the receiver operating characteristic curve (AUC) and the concordance index (C-index) were used to compare the predictive ability of nomograms and other staging systems. Results: The modified Glasgow Prognostic Score (mGPS) was identified as the prognostic factor for both overall survival (OS) and progression-free survival (PFS). The nomograms built on the prognostic factors showed powerful efficacy in survival prediction, with C-indexes of 0.800 (95% CI 0.767-0.833) and 0.752 (95% CI 0.718-0.786) for OS and PFS in the primary cohort, 0.659 (95% CI 0.586-0.732) and 0.638 (95% CI 0.571-0.705) for OS and PFS in the validation cohort, respectively. Compared with tumor-node-metastasis stage, Barcelona Clinic Liver Cancer staging score, Cancer of the Liver Italian Program score, and Okuda staging system, the nomograms had significantly higher values of AUC and C-indexes in survival prediction in the primary and validation cohorts. Conclusion: Compared with currently used staging systems, the nomograms showed significantly higher efficacy in predicting survival of ICC patients after resection. The nomograms provide new versions of personalized management for these patients.

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Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers

Cited by 24 publications

References 54 publications

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

Low expression of IL6R predicts poor prognosis for lung adenocarcinoma

An Inflammation-Index Signature Predicts Prognosis of Patients with Intrahepatic Cholangiocarcinoma After Curative Resection

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