Summary Down‐regulated chemerin expression has been reported to correlate with poor prognosis of several types of cancer including melanoma. All‐trans retinoic acid (atRA) is a potent inducer of chemerin, and we previously reported that atRA inhibited murine melanoma growth through enhancement of anti‐tumor T‐cell immunity. Here, we aimed to investigate whether loss of endogenous chemerin accelerated melanoma growth and whether chemerin was involved in the melanoma‐inhibitory effect of atRA. We demonstrated that chemerin was constitutively expressed in the skin, which was down‐regulated during murine melanoma growth. Rarres2−/− mice, which are deficient in chemerin, exhibited aggravated tumor growth and impaired tumor‐infiltrating natural killer (NK) cells that express CMKLR1, the functional receptor of chemerin. Topical treatment with atRA up‐regulated skin chemerin expression, which was primarily derived from dermal cells. Moreover, atRA treatment significantly enhanced tumor‐infiltrating NK cells, which was completely abrogated in Rarres2−/− mice and Cmklr1−/− mice, suggesting a dependency of NK cell recruitment on the chemerin–CMKLR1 axis in melanoma. Despite comparable melanoma growth detected in wild‐type mice and Cmklr1−/− mice, lack of CMKLR1 partially abrogated the melanoma‐inhibitory effect of atRA. This may be due to the inability to enhance tumor‐infiltrating NK cells in Cmklr1−/− mice following atRA treatment. Collectively, our study suggests that down‐regulation of chemerin could be a strategy used by cancers such as melanoma to impair anti‐tumor NK cell immunity and identifies a new anti‐tumor mechanism of atRA by up‐regulating chemerin to enhance CMKLR1‐dependent NK cell recruitment.

Background: There is currently a lack of clinical models to accurately predict the prognosis of cervical adenocarcinoma. This study aimed to explore the correlation between immune genes and the prognosis of cervical adenocarcinoma patients, and establish a prognostic model. Methods:Transcriptome sequencing data sets and clinical data sets of cervical adenocarcinoma samples were downloaded from the Gene Expression Omnibus (GEO) database. Information about the immune gene was obtained from the ImmPort database. Differentially expressed genes and differentially expressed immune genes were screened in cervical adenocarcinoma tissue and normal cervical group by edgeR package.Differentially expressed immune genes were screened for prognosis-related immune genes by Cox analysis. Taking the immune genes related to prognosis as variables, a prognosis prediction model was established by multivariate Cox regression analysis. Kaplan-Meier analysis and a receiver operating characteristic (ROC) curve were used to test the effectiveness of the model. According to the clinical information and risk score, univariate multivariate Cox analyses were used to screen the independent prognostic risk factors of cervical adenocarcinoma. Results: CXCL9 was an independent prognostic factor of cervical adenocarcinoma [hazard ratio (HR) =0.63; P=0.025]. CGB5 (HR =1.22; P=0.034), CXCL12 (HR =1.33; P=0.023), PTX3 (HR =1.53; P=0.024), and CXCL10 (HR =2.31; P=0.031) were prognostic risk factors for cervical adenocarcinoma. The risk score was calculated as follows: risk score = (0.005 × CXCL10) + (0.076 × CGB5) + (0.061 × CXCL12) + (0.034 × PTX3)+ (−0.004 × CXCL9). The prognosis of the low-risk score group was better than that of the high-risk score group (P=0.035). The area under the ROC curve (AUC) of the risk score was 0.713, and the predictive power was good. Multivariate Cox analysis showed that N stage (HR =1.34; P=0.035) and risk score (HR =1.37; P<0.001) were independent risk factors for the prognosis of cervical adenocarcinoma (HR >1; P<0.001).Conclusions: In this study, an immune gene prognosis prediction model for cervical adenocarcinoma was established based on the GEO and ImmPort databases. The prediction performance of the model is good, and the prognosis of patients can be evaluated according to the gene expression, which has clinical practicability.

Background: The effect of ovarian-sparing surgery versus ovariectomy on prognosis in early cervical adenocarcinoma is controversial. The aim of this study was to compare the effect of ovary preservation versus ovariectomy on the prognosis of patients with cervical adenocarcinoma.Methods: A literature search was conducted of the PubMed, Excerpta Medica Database, Medline, Central, China National Knowledge Infrastructure databases, and China Science Periodical Database. The subjects of the literature study were patients with cervical adenocarcinoma. The literature compared the prognostic impact of ovary-sparing versus ovariectomy surgery. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. The Chi-square test was used to test the heterogeneity of the articles, and the randomeffects model was used if the results indicated heterogeneity. A subgroup analysis and sensitivity analysis were used to examine the source of heterogeneity. If there was no heterogeneity among the articles, a fixed-effects model was used. Publication bias was evaluated using funnel plots and Egger test.Results: A total of 3,467 patients with stage IA-IB cervical adenocarcinoma from 5 articles were included in the meta-analysis, of whom 995 had ovarian preservation and 1,895 had ovariectomy. There was no statistically significant difference in the 5-year overall survival (OS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.14). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year progression free survival (PFS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.11). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year disease specific survival (DSS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.48). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05).Conclusions: There was no statistically significant difference in 5-year OS, PFS and DSS between ovarian-sparing surgery and oophorectomy for early-stage cervical adenocarcinoma. High-quality randomized controlled trials are still needed to verify this conclusion.