The association between preoperative serum interleukin‐6 levels and postoperative prognosis in patients with T2 gallbladder cancer

Wang, Jianfa; Liu, Jiazhe; Chang, Qimeng; Yang, Biao; Li, Sen; Gu, Chao

doi:10.1002/jso.25085

Cited by 10 publications

(6 citation statements)

References 45 publications

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“…Serum CA19-9 is the most evaluated prognostic biomarker in BTC and our data support the prognostic association, especially as a continuous variable prior to treatment. However, serum IL6 has previously been proposed to be associated with tumor burden and DFS (30,40,41), and IL6 and YKL-40 have been associated with OS in small studies of BTC (28,29,31), as well as in the larger ABC-03 trial for IL6 (32). Our results indicate a possible clinical utility of these inflammatory biomarkers measured at inclusion either in combination with CA19-9 or, in the case of IL6, providing warranted prognostic information in patients with BTC with normal levels of CA19-9.…”

Section: Discussionmentioning

confidence: 99%

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

Høgdall

O’Rourke

Dehlendorff

et al. 2020

Clinical Cancer Research

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Purpose: Biliary tract cancer (BTC) is a heterogeneous group of rare gastrointestinal malignancies with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL6 and YKL-40 compared with CA19-9 before and during palliative chemotherapy. We also investigated in mice whether IL6R inhibition in combination with gemcitabine could prolong chemosensitivity.Experimental Design: A total of 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February 2004 to March 2017. Serum CA19-9, IL6, and YKL-40 were measured before and during palliative treatment. Associations between candidate biomarkers and progression-free survival (PFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression. Effects of inhibiting IL6R and YKL-40 were assessed in vitro, and of IL6R inhibition in vivo.Results: High pretreatment levels of CA19-9, IL6, and YKL-40, and increasing levels during treatment, were associated with short PFS and OS in patients with advanced BTC. IL6 provided independent prognostic information, independent of tumor location and in patients with normal serum CA19-9. ROC analyses showed that IL6 and YKL-40 were predictive of very short OS (OS < 6 months), whereas CA19-9 was best to predict OS > 1.5 years. Treatment with anti-IL6R and gemcitabine significantly diminished tumor growth when compared with gemcitabine monotherapy in an in vivo transplant model of BTC.Conclusions: Serum IL6 and YKL-40 are potential new prognostic biomarkers in BTC. IL6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL6R should be considered as a new treatment option to sustain gemcitabine response in patients with BTC.

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Section: Discussionmentioning

confidence: 99%

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

Høgdall

O’Rourke

Dehlendorff

et al. 2020

Clinical Cancer Research

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“…[109,110] serum IL-6 ECLIA Low levels correlated with a better 5-year overall survival rate in a subgroup of patients with hepatic side tumors (n = 69). [111] preoperative NLR Hemogram…”

Section: Molecular Prognostic Biomarkersmentioning

confidence: 99%

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

García

Lamarca

Díaz

et al. 2020

Cancers

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Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.

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“…A total of 27 studies 9 , 10 , 17 , 23 , 28 – 33 , 35 , 37 , 38 , 40 – 44 , 46 , 49 , 50 , 52 – 57 with 10 164 cases were incorporated. Pooled results indicated that poorly differentiated tumor was a risk factor for OS among resected cases with GBC (HR=3.22, 95% CI: 1.65–2.87, P <0.00001) (Figure S1J, Supplemental Digital Content 4, http://links.lww.com/JS9/C302 ) (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 3 studies 50 , 52 , 55 with 617 cases were incorporated. Pooled results indicated that hepatic tumor shared more worse prognosis than peritoneal tumor and tumor location (peritoneal side vs hepatic side) was a prognostic factor for resected GBC (HR=1.85, 95% CI: 1.51–2.28, P <0.00001) (Figure S1L, Supplemental Digital Content 4, http://links.lww.com/JS9/C302 ) (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Prognostic factors for resected cases with gallbladder carcinoma: a systematic review and meta-analysis

Lv,

Wang,

et al. 2024

International Journal of Surgery

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Objective: Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival (OS) among resected cases with gallbladder carcinoma (GBC). Methods: PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval (CI) were directly extracted from the original study or roughly estimated via Tierney’s method. Standard Parmar modifications were used to determine pooled HRs. Results: A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P=0.00020), concurrent gallstone disease (HR=1.22, P=0.00200), elevated preoperative CA199 level (HR=1.93, P<0.00001), advanced T stage (HR=3.09, P<0.00001), lymph node metastasis (HR=2.78, P<0.00001), peri-neural invasion (HR=2.20, P<0.00001), lymph-vascular invasion (HR=2.37, P<0.00001), vascular invasion (HR=2.28, P<0.00001), poorly differentiated tumor (HR=3.22, P<0.00001), hepatic side tumor (HR=1.85, P<0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P<0.00001), combined bile duct resection (HR=1.45, P<0.00001), and positive surgical margin (HR=2.90, P<0.00001) were well-established prognostic factors. Pathological subtypes (P=0.53000) and postoperative adjuvant chemotherapy (P=0.70000) were not prognostic factors. Pooled results of multi-variate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. Conclusion: Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

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The association between preoperative serum interleukin‐6 levels and postoperative prognosis in patients with T2 gallbladder cancer

Abstract: Preoperative serum IL-6 is significantly associated with prognostic implications in patients with hepatic side T2 GBC, not in those with peritoneal side tumors.

Cited by 10 publications

References 45 publications

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

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

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

Prognostic factors for resected cases with gallbladder carcinoma: a systematic review and meta-analysis

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