Identification of prognosis-related cyclin-dependent kinases and potential response drugs in hepatocellular carcinoma.

Context and Aims: Which cyclin-dependent kinases (CDKs) involved in the progress of hepatocellular carcinoma (HCC) need to be further clarified. To identify prognostic-relevant biomarkers in HCC through a systematic investigation of the prognostic value of CDKs. Methods and Material: We explored the relationship between CDKs expression and the prognosis of patients with HCC using multiple online databases. In addition, their biological functions and correlation with the immune system and drug response were investigated. Results: Among the 20 CDKs (CDK1 ~20) altered in HCC, the significantly high expression of CDK1 and CDK4 in patients with HCC was significantly associated with worse prognosis. Interestingly, CDK1 had significant co-occurrence with CDK4 and CDK1-related and CDK4-related signaling pathways are closely related to hepatitis virus-related HCC. We identified multiple transcription factors of CDK1 and CDK4; of those, only four (E2F1, PTTG1, RELA, and SP1) were significantly associated with the prognosis of HCC patients. Genetic alterations in CDKs were significantly correlated with disease-free and progression-free survival, which may be associated with aberrant expression of progesterone receptor. Moreover, we found a significantly positive correlation between CDK1 and CDK4 expression and tumor-infiltrating activated CD4+ T cell and exhausted T cell-related signature. Finally, we identified drugs with good potential prognostic value predicted by CDK1 and CDK4 levels. Conclusions: CDK1 and CDK4 may be potential prognostic biomarkers for HCC. Moreover, targeting four transcription factors (E2F1, PTTG1, RELA, and SP1) combined with immunotherapy may be a new therapeutic strategy for treating HCC patients with high CDK1 and CDK4 expression, especially hepatitis-related HCC.

The relationship between the efficacy of thermal ablation and inflammatory response and immune status in early hepatocellular carcinoma and the progress of postoperative adjuvant therapy.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Thermal ablation has the advantages of being equivalent to surgical resection, minimally invasive, low cost and significantly reducing hospital stay. Therefore, it is recommended as one of the first-line radical treatment for early HCC. However, with the deepening of research on early HCC, more and more studies have found that not all patients with early HCC can obtain similar efficacy after radical thermal ablation, which may be related to the heterogeneity of HCC. Previous studies have shown that inflammation and immunity play an extremely important role in the prognostic heterogeneity of patients with HCC. Therefore, the inflammatory response and immune status of patients may be closely related to the efficacy of early HCC after curative thermal ablation. This article elaborates the mechanism of high inflammatory response and poor immune status in the poor prognosis after radical thermal ablation of early HCC, and clarifies the population who may benefit from adjuvant therapy after radical thermal ablation in patients with early HCC, which provides a new idea for the precise adjuvant treatment after radical ablation of early HCC in the future.

Intermediate stage hepatocellular carcinoma: Comparison of the value of inflammation-based scores in predicting progression-free survival of patients receiving transarterial chemoembolization.

CONTEXT AND AIMS: The identification of inflammation-related prognostic heterogeneity in intermediate-stage hepatocellular carcinoma (HCC) can reveal more effective first-line treatments. Our study aimed to compare the intermediate-stage HCC patients' different inflammation-based scores in predicting their progression-free survival (PFS) after transarterial chemoembolization (TACE). MATERIALS AND METHODS: We analyzed retrospectively a total of 128 intermediate-stage HCC patients who received first-line TACE treatment. We used the Cox-proportional hazards modeling to identify the independent prognostic factors. We compared the inflammation-based scores abilities to predict the PFS through the time-dependent receiver operating characteristic curves and area under the curves. RESULTS: The multivariate analysis showed that tumor size and platelet-to-lymphocyte ratio (PLR) were the independent prognostic factors for PFS (P < 0.05). The PLR predicted the intermediate-stage HCC patients' PFS receiving the TACE treatment better than other inflammation-based scores (e.g., the neutrophil-to-lymphocyte ratio, the Glasgow Prognostic Score (GPS), the modified GPS, the Prognostic Index, the Prognostic Nutritional Index, the lymphocyte-to-monocyte ratio, and the systemic immune-inflammation index) (P < 0.05). An easy-to-use novel inflammation score based on tumor size - PLR-size score significantly improved the PFS prediction performance (P < 0.05). CONCLUSIONS: As a first-line treatment, TACE was not well suitable for all intermediate-stage HCC patients, while the PLR was a better inflammation-based score than others. Tumor size should be regarded as an essential variable in affecting intermediate-stage HCC patients' first-line treatment strategies.

Socioeconomic status predicts the risk of stroke death: A systematic review and meta-analysis.

Low socioeconomic status appears to be an independent risk factor for stroke mortality in epidemiology studies, but there has been no systematic assessment of this association. We performed a systematic review and meta-analysis evaluating the association between low socioeconomic status and stroke mortality. A systematic review of MEDLINE, EMBASE, and Web of Science for cohort studies that reported low socioeconomic status and stroke mortality was conducted from inception until July 2017. Research information, adjusted risk ratio (RR) estimates and 95% confidence intervals (Cls) were extracted. Estimates were pooled using a random-effects model. Heterogeneity was examined using the Q statistic and I 2. Twenty-seven prospective cohort studies (471,354,852 subjects; 429,886 deaths) assessing stroke mortality with low socioeconomic status were identified. Compared with the highest socioeconomic status, overall RR of stroke mortality was 1.39 (95% CI, 1.31-1.48) for those with the lowest after adjustment for confounding factors, but there was substantial heterogeneity between studies (I 2 = 89.9%, P = 0.001). Significant relationships were observed between risk of stroke mortality and the lowest education (RR = 1.21, 95% CI 1.11-1.33; I 2 = 70.9%, P < 0.001), income (RR = 1.54, 95% CI 1.30-1.82; I 2 = 91.6%, P < 0.001), occupation (RR = 1.54, 95% CI 1.35-1.75; I 2 = 78.3%, P < 0.001), composite socioeconomic status (RR = 1.37, 95% CI 1.25-1.51; I 2 = 69.5%, P = 0.001). After subgroup analysis, it was found that the heterogeneity of each SES indicator mainly came from the follow-up time, study population, stroke type, study area. Patients with low socioeconomic status had a higher risk of stroke mortality. The heterogeneity of income and occupation is larger, and the education and composite SES is smaller.

Association between socioeconomic status and prognosis after ischemic stroke in South China.

Background: Previous studies have conflicting results on the association between socioeconomic status and stroke outcomes. Thus, this study aimed to investigate whether socioeconomic status is associated with the prognosis of ischemic stroke in Guangzhou, South China. Methods: A total of 622 patients with ischemic stroke who were admitted in the neurology department of five general hospitals in Guangzhou from May 2014 to October 2014 were included in the study. Socioeconomic status was measured based on education, income, caregiver, and insurance. The modified Rankin scale was used to evaluate the two years prognosis of patients with stroke. A multivariate logistic regression model was performed to determine the association between socioeconomic status and ischemic stroke prognosis. Results: In 2 years follow-up, 542 ischemic stroke patients were interviewed by telephone. Age ranged from 31 to 96 years, 65.5% of the patients were male. 33.9% of patients with ischemic stroke had a poor prognosis. After adjustment for age, sex, cardiovascular disease, behavior lifestyle, and severity of stroke, odds ratio for poor prognosis in patients with low income was 1.84 (95%CI 1.05-3.22), family caregiver 3.19 (95%CI 1.05-9.70), and no insurance 1.68 (95%CI 1.02-2.77). Conclusions: Patients with low income, family caregiver, and no insurance have a poorer prognosis after ischemic stroke that can be partly explained by intermediate variable in the patients' demographic characteristics, cardiovascular disease, behavior lifestyle, and stroke severity. Abbreviations: DALYs: disability-adjusted life years; SES: socioeconomic status; FMC: free medical care; MIUR: medical insurance for urban residents; MIUE: medical insurance for urban employees; NCMS: new rural cooperative medical scheme ; NIHSS: National Institute of Health Stroke Scale ; mRS: modified Rankin scale; OR: odds ratios; CI: confidence interval.

Effects of socioeconomic status on risk of ischemic stroke: a case-control study in the Guangzhou population.

BACKGROUND: The association between socioeconomic status (SES) and stroke risk remains controversial around the world. It is not clear that the effect of SES on stroke in China due to the lack of relevant research. We aimed to assess the association between SES and risks of first-ever ischemic stroke in Guangzhou, China. METHODS: Cases were recruited from neurology department in the First Affiliated Hospital of Guangdong Pharmaceutical University during September 2016-October 2017. Age- and sex-matched controls were derived from surgical departments, over the same period. SES was assessed based on education, occupation, and income. Education was divided into ≤6 years, 6-9 years, 10-12 years, and > 12 years. Family monthly income per capita was categorized into ≤¥1000, ¥1001-3000, ¥3001-5000, and > ¥5001. Occupation was stratified into manual, non-manual, no job, and retired. A multivariate logistic regression model was used to determine the association between SES and risk of ischemic stroke. RESULTS: In total, 347 ischemic stroke patients and 347 controls were recruited, with mean ages of 60.54 ± 13.13 and 60.56 ± 13.07 years, respectively. After adjusting for confounding factors, odds ratio (OR) for 6-9 years of education was 2.63 (95% confidence interval [CI] 1.45-4.75); > 12 years, 2.18 (1.25-3.82) compared with those for < 6 years of education. ORs for the second lowest, third lowest, and highest incomes were 1.96 (1.21-3.15), 4.16 (2.39-7.22), and 2.83(1.25-6.39), respectively, compared with those for the lowest income. ORs for manual workers and non-manual workers were 1.95 (1.23-3.07) and 1.87 (1.05-3.33), compared with individuals without jobs. CONCLUSIONS: Higher SES is positively related with risks of ischemic stroke, explained by cardiovascular diseases and unhealthy lifestyles in Guangzhou, China. Thus, effective strategies such as extensive health education, promoting a healthy lifestyle, screening for risk factors to prevent stroke should be implemented to reduce ischemic stroke incidences among the high SES group.