Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies

Koshiol, Jill; Castro, Felipe A.; Kemp, Troy J.; Gao, Yu Tang; Roa, Juan Carlos; Wang, Bingsheng; Nogueira, Letícia; Araya, J. C.; Shen, Ming; Rashid, Asif; Hsing, Ann W.; Hildesheim, Allan; Ferreccio, Catterina; Pfeiffer, Ruth M.; Pinto, Lígia A.

doi:10.1016/j.cyto.2016.05.003

Cited by 27 publications

(50 citation statements)

References 32 publications

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“…We replicated the results from the Shanghai study in patients with GBC from the Chile Gallbladder Cancer Study, a study from which we had data on circulating inflammatory proteins and survival. Details about the Chile Gallbladder Cancer Study have been published 14 , 26 . Briefly, between April 2012 and August 2013, we recruited 52 GBC cases newly diagnosed at cancer referral hospitals in Santiago, Concepción, and Temuco, with a participation rate of 85%.…”

Section: Methodsmentioning

confidence: 99%

Circulating Levels of Inflammatory Proteins and Survival in Patients with Gallbladder Cancer

Liu

Kemp

Gao

et al. 2018

Sci Rep

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Although inflammation is central to gallbladder cancer (GBC) development and proliferation, no study has systematically investigated circulating inflammatory proteins and patient survival. We aimed to examine whether the circulating levels of inflammatory proteins is associated with all-cause mortality among such patients. We recruited 134 patients with newly diagnosed with GBC from 1997 to 2001 in a population-based study in Shanghai and an independent set of 35 patients from 2012 to 2013 in Chile. Cox proportional hazards regression models adjusted for covariates were used to evaluate the hazard ratios (HRs) for death by serum levels of 49 inflammatory proteins (quartiles). Of 49 evaluable proteins, eight were significantly associated with overall survival. Seven were associated with a poorer survival, while the highest levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were associated with an increase in survival (HR = 0.26, 95% CI = 0.14, 0.47). No substantial difference in the magnitude of the association was observed between early- and late-stages of GBC. Of seven proteins, five were validated in the patients from Chile. Reducing inflammation and targeting pathways associated with increased survival might improve GBC outcomes. The potential for using a TRAIL-related anticancer drug for GBC treatment merits further investigation.

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Section: Methodsmentioning

confidence: 99%

Circulating Levels of Inflammatory Proteins and Survival in Patients with Gallbladder Cancer

Liu

Kemp

Gao

et al. 2018

Sci Rep

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“…Previous studies have shown that serum levels of IP-10 (CXCL10) are elevated in BC patients compared to controls, 29 and also in patients with other malignancies. 30,31 Here, we provide evidence that breast tumor tissues secrete more IP-10 than non-tumoral tissues in the same patient. Higher IP-10 secretion also correlated with T-cell infiltration, particularly in the TNBC subtype.…”

Section: Discussionmentioning

confidence: 61%

Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics

et al. 2016

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The tumor microenvironment is composed of many immune cell subpopulations and is an important factor in the malignant progression of neoplasms, particularly breast cancer (BC). However, the cytokine networks that coordinate various regulatory events within the BC interstitium remain largely uncharacterized. Moreover, the data obtained regarding the origin of cytokine secretions, the levels of secretion associated with tumor development, and the possible clinical relevance of cytokines remain controversial. Therefore, we profiled 27 cytokines in 78 breast tumor interstitial fluid (TIF) samples, 43 normal interstitial fluid (NIF) samples, and 25 matched serum samples obtained from BC patients with Luminex xMAP multiplex technology. Eleven cytokines exhibited significantly higher levels in the TIF samples compared with the NIF samples: interleukin (IL)-7, IL-10, fibroblast growth factor-2, IL-13, interferon (IFN)γ-inducible protein (IP-10), IL-1 receptor antagonist (IL-1RA), platelet-derived growth factor (PDGF)-β, IL-1β, chemokine ligand 5 (RANTES), vascular endothelial growth factor, and IL-12. An immunohistochemical analysis further demonstrated that IL-1RA, IP-10, IL-10, PDGF-β, RANTES, and VEGF are widely expressed by both cancer cells and tumor-infiltrating lymphocytes (TILs), whereas IP-10 and RANTES were preferentially abundant in triple-negative breast cancers (TNBCs) compared to Luminal A subtype cancers. The latter observation corresponds with the high level of TILs in the TNBC samples. IL-1β, IL-7, IL-10, and PDGFβ also exhibited a correlation between the TIF samples and matched sera. In a survival analysis, high levels of IL-5, a hallmark T2 cytokine, in the TIF samples were associated with a worse prognosis. These findings have important implications for BC immunotherapy research.

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“…Part of this validation collective has been previously described by Koshiol et al [18] Table 4 shows selected characteristics of individuals in the validation study, and Fig 4D depicts the four family pedigrees.…”

Section: Methodsmentioning

confidence: 99%

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile

et al. 2017

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Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention.Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

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Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies

Cited by 27 publications

References 32 publications

Circulating Levels of Inflammatory Proteins and Survival in Patients with Gallbladder Cancer

Circulating Levels of Inflammatory Proteins and Survival in Patients with Gallbladder Cancer

Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile

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