Interleukin‐34, a comprehensive review Baghdadi, Muhammad; Umeyama, Yui; Hama, Naoki ...
Journal of leukocyte biology,
November 2018, Letnik:
104, Številka:
5
Journal Article
Recenzirano
Odprti dostop
IL‐34 is a novel cytokine that was identified in 2008 in a comprehensive proteomic analysis as a tissue‐specific ligand of CSF‐1 receptor (CSF‐1R). IL‐34 exists in all vertebrates including fish, ...amphibians, birds, and mammals, showing high conservation among species. Structurally, IL‐34 belongs to the short‐chain helical hematopoietic cytokine family but shows no apparent consensus structural domains, motifs, or sequence homology with other cytokines. IL‐34 is synthesized as a secreted homodimeric glycoprotein that binds to the extracellular domains of CSF‐1R and receptor‐type protein‐tyrosine phosphatase‐zeta (PTP‐ζ) in addition to the chondroitin sulfate chains of syndecan‐1. These interactions result in activating several signaling pathways that regulate major cellular functions, including proliferation, differentiation, survival, metabolism, and cytokine/chemokine expression in addition to cellular adhesion and migration. In the steady state, IL‐34 contributes to the development and maintenance of specific myeloid cell subsets in a tissue‐specific manner: Langerhans cells in the skin and microglia in the brain. In pathological conditions, changes in IL‐34 expression—increased or decreased—are involved in disease pathogenesis and correlate with progression, severity, and chronicity. One decade after its discovery, IL‐34 has been introduced as a newcomer to the big family of interleukins with specific physiological functions, critical pathological roles, and promising clinical applications in disease diagnosis and treatment. In this review, we celebrate the 10th anniversary of IL‐34 discovery, introducing its biological characteristics, and discussing the importance of IL‐34 signaling network in health and disease.
IL‐34, a newcomer to the big family of interleukins with specific physiological functions and critical pathological roles.
Background
Malnutrition is an independent risk factor for postoperative mortality and morbidity in major gastrointestinal surgery. The aim of this study was to investigate the prevalence of ...malnutrition and identify the optimal preoperative nutritional support for preventing postoperative surgical site infections (SSIs) in malnourished gastric cancer patients undergoing gastrectomy.
Methods
We analyzed 800 patients with gastric cancer who underwent gastrectomy. Nutritional risk factors included weight loss >10 % within 6 months, body mass index <18.5 kg/m
2
, Subjective Global Assessment Grade C, and serum albumin <3.0 g/dl. Adequate energy intake was defined as receiving ≥25 kcal/kg ideal body weight per day. Optimal nutritional support was examined in terms of both duration and calorie intake.
Results
Overall, 152 patients (19.0 %) were classified as malnourished. The incidence of SSIs was significantly higher in malnourished patients than in well-nourished patients (35.5 vs. 14.0 %;
p
< 0.0001). The incidence of SSIs in malnourished patients was significantly lower in the well-supported group receiving adequate energy support for at least 10 days than in the poorly-supported group, which received inadequate or no energy support or adequate energy support for <10 days (17.0 vs. 45.4 %;
p
= 0.0006). In multivariate analysis, well-managed nutritional support was identified as an independent factor associated with fewer SSIs (odds ratio 0.14; 95 % confidence interval 0.05–0.37;
p
= 0.0002).
Conclusions
Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients.
Background
Malignancy is a secondary cause of sarcopenia, which is associated with impaired cancer treatment outcomes. The aim of this study was to investigate the prevalence of preoperative ...sarcopenia among elderly gastric cancer patients undergoing gastrectomy and the differences in preoperative dietary intake and postoperative complications between sarcopenic and non-sarcopenic patients.
Methods
Ninety-nine patients over 65 years of age who underwent gastrectomy for gastric cancer were analyzed. All patients underwent gait and handgrip strength testing, and whole-body skeletal muscle mass was measured using a bioimpedance analysis technique based on the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm for the evaluation of sarcopenia before surgery. Preoperative dietary intake was assessed using a food frequency questionnaire.
Results
Of these patients, 21 (21.2 %) were diagnosed with sarcopenia. Sarcopenic patients consumed fewer calories and less protein preoperatively (23.9 vs. 27.8 kcal/kg ideal weight/day and 0.86 vs. 1.04 g/kg ideal weight/day;
P
= 0.001 and 0.0005, respectively). Although the overall incidence of postoperative complications was similar in the two groups (57.1 % vs. 35.9 %;
P
= 0.08), the incidence of severe (Clavien–Dindo grade ≥ IIIa) complications was significantly higher in the sarcopenic group than in the non-sarcopenic group (28.6 % vs. 9.0 %;
P
= 0.029). In the multivariate analysis, sarcopenia alone was identified as a risk factor for severe postoperative complications (odds ratio, 4.76; 95 % confidence interval, 1.03–24.30;
P
= 0.046).
Conclusions
Preoperative sarcopenia as defined by the EWGSOP algorithm is a risk factor for severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy.
Abstract Background Recently, several preoperative proinflammatory markers and nutritional factors such as neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) have been reported ...as significant predictor for poor prognosis of various malignant tumors. In this study, we evaluated the prognostic values of these preoperative parameters in patients with resectable pancreatic head cancer. Methods We retrospectively reviewed consecutive patients who underwent PD for pancreatic head cancer between 2007 and 2012. A total of 46 patients were enrolled in this analysis. Preoperative parameters such as CRP, CA19-9, NLR and PNI at the time of presentation were recorded as well as overall survival. Cancer specific survival was assessed using Kaplan–Meier method. Univariate and multivariate Cox regression models were applied to evaluate the prognostic relevance of preoperative parameters. The correlations between CA19-9 values, NLR and pathological findings, first recurrence site were respectively reviewed. Results In multivariable analysis preoperative high NLR (≧2.7) and high CA19-9 (≧230) were independent prognostic factors for poor survival (P value: 0.03 and 0.025, respectively). Kaplan–Meier survival analysis demonstrated the overall 2-year survival rate in patients with high NLR or high CA19-9 were 37.5% compared with 89.9% in patients with low NLR and low CA19-9. Conclusion Preoperative NLR and serum CA19-9 offer significant prognostic information associated with overall survival following PD in the patients with pancreatic head cancer.
Purpose
To evaluate the efficacy and safety of the enhanced recovery after surgery (ERAS) protocol and quantify the impact of each ERAS item on postoperative outcomes.
Methods
We used a generalized ...linear model to compare 289 colorectal cancer patients treated with the ERAS protocol between June, 2015 and April, 2021, with 99 colorectal cancer patients treated with the conventional colorectal surgery pathway between April, 2014 and June, 2015.
Results
The median length of hospital stay (LOHS) was significantly shorter in the ERAS group, at 9 days (range 3–104 days) vs. 14 days (range 4–44 days) (
p
< 0.001), but the complication rates (Clavien–Dindo grade 2 or more) were similar (16.6% vs. 22.2%;
p
= 0.227). However, in the ERAS group, the higher the compliance with ERAS items, the lower the complication rate and LOHS (both
p
< 0.001). Multiple regression analysis demonstrated that "Discontinuation of continuous intravenous infusion on POD1" and "Avoidance of fluid overload" were significantly associated with the LOHS (
p
< 0.001 and
p
= 0.008).
Conclusion
The ERAS protocol is safe and effective for elective colorectal cancer surgery, and compliance with the ERAS protocol contributes to shorter LOHS and fewer complications. Items related to perioperative fluid management had a crucial impact on these outcomes.
Abstract
Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are ...diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.
Potential roles for IL-34 in ovarian cancer
Biliary tract cancer (BTC) has a generally poor prognosis. Furthermore, it is difficult to distinguish BTC from benign biliary disease (BBD) with commonly used modalities. Therefore, a novel ...biomarker to facilitate cancer detection is highly desirable. Recent studies have reported the use of circulating microRNAs (miRNAs) as biomarkers for cancers. The purpose of this study was to evaluate whether circulating miRNA‐21 (miR‐21) could be used as a biomarker for BTC. Plasma samples were obtained from 94 BTC patients, 50 healthy volunteers (HVs), and 23 BBD patients. miR‐21 levels in the samples were measured by qRT‐PCR. Plasma miR‐21 levels in patients with BTC were significantly higher than in HVs or in patients with BBD (P < 0.0001 for both). Receiver–operator curve (ROC) curve analysis in differentiating BTC patients from HVs indicated that area under the curve (AUC), optimal sensitivity and specificity was 0.93, 85.1% and 100%, respectively, and those in differentiating BTC patients from BBD patients was 0.83, 72.3%, 91.3%, respectively. Validation of these results indicated that the negative predictive value, positive predictive value, sensitivity, specificity, and accuracy in differentiating BTC patients from HVs was 76.6%, 98.6%, 84.0%, 98.0%, and 88.9%, respectively, and those in differentiating BTC patients from BBD patients was 42.2%, 93.0%, 71.2%, 82.6%, and 72.6%, respectively. These sets of values were improved by combining miR‐21 and CA19‐9 measurements. Plasma miR‐21 is a novel diagnostic biomarker for BTC, and may be useful in distinguishing between BTC and BBD patients.
In the present study, we evaluated the usefulness of plasma miR‐21 as a diagnostic biomarker for biliary tract cancer (BTC). Judging solely by CA19‐9 levels, many BTC patients were within the normal range. More BTC patients could be diagnosed by miR‐21 levels. (Black circle, BTC patients; blue circle, HVs; red circle, BBD patients).
Pancreatic cancer has a poor prognosis because of its high invasiveness and recurrence, and these properties closely link to the phenomenon of epithelial-mesenchymal transition (EMT). Recently, it ...has been reported that Sox4 is indispensable for EMT in vitro and in vivo and regulates various master regulators of EMT including Zeb, Twist and Snail. Moreover, Sox4 induces the transcription of Ezh2 which is the histone methyltransferase, and reprograms the cancer epigenome to promote EMT and metastasis. Therefore, the present study evaluated the importance of Sox4, Ezh2 and miR-335, which regulate Sox4 expression epigenetically, in clinical samples with pancreatic cancer. This retrospective analysis included data from 36 consecutive patients who underwent complete surgical resection for pancreatic cancer and did not undergo any preoperative therapies. We assessed the clinical significance of Sox4/Ezh2 axis and miR-335 expression, using immunohistochemistry and qRT-PCR with laser captured microdissection (LCM). The Sox4 positive patients had significantly worse prognosis as for disease-free survival (DFS) (P=0.0154) and the Ezh2-positive patients had significantly worse prognosis as for overall survival (OS) (P=0.0347). The miR-335 expression was inversely correlated with Sox4 expression in the identical clinical specimens, but it was not related to the prognosis. Sox4/Ezh2 axis was closely associated with the prognosis in pancreatic cancer patients.
Purpose
The aim of this study was to determine the utility of the peritoneal lavage cytology findings in predicting the clinical outcomes of resectable left-sided pancreatic cancer.
Methods
...Peritoneal lavage samples were collected from 39 consecutive patients who underwent surgery for left-sided pancreatic cancer between January 2000 and December 2010. We analyzed the correlations between the peritoneal lavage cytology findings and the clinical outcomes.
Results
Five patients (12.8 %) had malignant cells in the cytology samples (positive cytology). This occurred more frequently in patients with vascular invasion (
P
= 0.008). Positive cytology was significantly associated with lower overall (
P
= 0.0007) and recurrent-free (
P
< 0.0001) survival rates. Positive cytology was an independent prognostic factor for recurrence (
P
= 0.022); it was closely associated with local recurrence, peritoneal recurrence and distant metastasis.
Conclusion
Surgeons should carefully consider the intraoperative diagnosis of peritoneal lavage cytology in patients with resectable left-sided pancreatic cancers, because patients with positive cytology are likely to experience recurrence.
Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; ...however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME).
In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34.
We found that
was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1
DC-CD8
T cell axis, however, it is canceled by the presence of IL-34.
These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.
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