Purpose: Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. Materials and Methods: Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints. Results: Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy. Conclusion High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.

Objective To investigate the prevalence and correlates of depression in residents aged 15 and older in Hainan province.Methods Stratified multistage random sampling methods were utilized to identify 12 117 individuals (≥15 years old) from 59 villages (neighborhoods) in 24 towns (streets) within 6 counties (cities) in Hainan Province from September 2010 to November 2011.The subjects were screened with an expanded version of the General Health Questionnaire (GHQ-12) and the respondents were divided into three groups by high risk,moderate risk and low risk of mental disorder,followed by formal diagnosis according to the Structured Clinical Interview for DSM-IV-TR (SCID-I/P) by psychiatrists among 100％ subjects in group with high risk,40％ subjects in group with moderate risk and 10％ subjects in group with low risk.The adjusted rate,standardized rate,and 95％ confidence interval (95％CI) of the one-month and lifetime prevalence were also calculated among the 3 groups of individuals who were diagnosed with depressive disorder.The difference in whether they suffered depression was determined by the chi-squared test.Correlations to depressive disorder and the odds ratio (OR) were explored with multiple regression analysis.Results There were 97 cases of depressive disorders (1-month) and 166 cases of lifetime depressive disorders finally confirmed.The adjusted rate of 1-month prevalence was 1.38％ (95％CI:1.12-1.59) and the life-time adjusted prevalence rate was 2.80％ (95％CI:2.51-3.09).Female (OR=1.55,95％CI:1.12-2.14),mid-age(50-64 y,OR=1.84,95％CI:1.13-2.99),being divorced or living separated (OR=4.87,95％CI:1.86-12.73),suffering chronic diseases (OR=2.19,95％CI:1.56-3.07),and low family income were significantly associated with suffering depressive disorder.Conclusions The prevalence of the depressive disorder among residents aged 15 and older in Hainan province is lower than the nationwide prevalence.People who are female,mid-age,being divorced or not living with the partner,earning a low income,and suffering chronic diseases have more predisposition to develop the depressive disorder in Hainan province.

Objective To investigate the prevalence and correlates of depression in residents aged 15 and older in Hainan province.Methods Stratified multistage random sampling methods were utilized to identify 12 117 individuals (≥15 years old) from 59 villages (neighborhoods) in 24 towns (streets) within 6 counties (cities) in Hainan Province from September 2010 to November 2011.The subjects were screened with an expanded version of the General Health Questionnaire (GHQ-12) and the respondents were divided into three groups by high risk,moderate risk and low risk of mental disorder,followed by formal diagnosis according to the Structured Clinical Interview for DSM-IV-TR (SCID-I/P) by psychiatrists among 100％ subjects in group with high risk,40％ subjects in group with moderate risk and 10％ subjects in group with low risk.The adjusted rate,standardized rate,and 95％ confidence interval (95％CI) of the one-month and lifetime prevalence were also calculated among the 3 groups of individuals who were diagnosed with depressive disorder.The difference in whether they suffered depression was determined by the chi-squared test.Correlations to depressive disorder and the odds ratio (OR) were explored with multiple regression analysis.Results There were 97 cases of depressive disorders (1-month) and 166 cases of lifetime depressive disorders finally confirmed.The adjusted rate of 1-month prevalence was 1.38％ (95％CI:1.12-1.59) and the life-time adjusted prevalence rate was 2.80％ (95％CI:2.51-3.09).Female (OR=1.55,95％CI:1.12-2.14),mid-age(50-64 y,OR=1.84,95％CI:1.13-2.99),being divorced or living separated (OR=4.87,95％CI:1.86-12.73),suffering chronic diseases (OR=2.19,95％CI:1.56-3.07),and low family income were significantly associated with suffering depressive disorder.Conclusions The prevalence of the depressive disorder among residents aged 15 and older in Hainan province is lower than the nationwide prevalence.People who are female,mid-age,being divorced or not living with the partner,earning a low income,and suffering chronic diseases have more predisposition to develop the depressive disorder in Hainan province.