Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis.

BACKGROUND: A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis. METHODS: Literatures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients' survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. RESULTS: Seven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients' overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) (P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18-0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than 'immunoreactive score (IRS)>5' and 'IRS > 25', high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30-0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country (P = 0.657), pathological type (P = 0.614), molecular type (P = 0.423), staining location (P = 0.481), or cut-off value (P = 0.509). CONCLUSIONS: The protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.

Prognostic role of pre-treatment C-reactive protein/albumin ratio in esophageal cancer: a meta-analysis.

BACKGROUND: In recent years, the role of pre-treatment C-reactive protein/albumin ratio (CAR) in prognosis of esophageal cancer (EC) has been investigated by several studies. This meta-analysis aimed to provide a more accurate and objective assessment of the prognostic value of pre-treatment CAR in EC. METHODS: Studies assessing the role of pre-treatment CAR in prognosis of EC were searched from PubMed, Embase and the Cochrane Library (last update by April 16, 2019). The hazard ratios (HRs) of CAR and the corresponding 95% CIs for overall survival (OS) or cancer-specific survival (CSS) in EC were extracted for pooled analysis. RESULTS: A total of eight observational studies including 2255 patients were collected. The pooled analysis showed that high CAR was related to worse OS in EC (pooled HR = 1.81; 95% CI = 1.40-2.35; P < 0.001). Subgroup analyses showed that the negative correlation between the CAR and OS was consistently demonstrated in subgroups stratified by country, pathological type, and cut-off value (P < 0.05). However, there was no relation between CAR and OS in subgroup of patients receiving neoadjuvant chemotherapy at a proportion of 100% (HR = 1.15, 95% CI = 0.56-2.69; P = 0.715). In addition, high CAR was also related to worse CSS in EC (pooled HR = 2.61; 95% CI = 1.67-4.06; P < 0.001). CONCLUSIONS: High pre-treatment CAR was an adverse prognostic factor for EC patients. More large-sample clinical trials are still needed to verify the prognostic value of pre-treatment CAR in EC.

Prognostic role of vitamin D receptor in digestive system tumours: A systematic review and preliminary meta-analysis.

The prognostic value of vitamin D receptor (VDR) in a variety of digestive system tumours remains controversial. In view of this, we conducted a meta-analysis. Published studies (as of Mar 30, 2023) assessing the prognostic role of VDR in digestive system tumours were retrieved. Pooled analyses were conducted based on the hazard ratios (HRs) of high VDR expression extracted from the included studies. If heterogeneity was detected, the random-effects model was used; otherwise, the fixed-effects model was used. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. Eight studies with 3,109 patients were included. The pooled results indicated that patients with high VDR expression generally had better overall survival (OS) (pooled HR = 0.67; 95% CI = 0.53-0.85; P = 0.001). Subgroup analyses showed that tumour type was the variable affecting the association between VDR expression and OS. VDR expression in colorectal cancer was not associated with OS (pooled HR = 0.84; 95% CI = 0.68-1.03; P = 0.086). We eliminated publication bias using the "trim and fill" method and found that high VDR expression remained an indicator of good OS (P = 0.001). Only a few studies explored the relationship between VDR expression and cancer-specific survival (CSS) or progression-free survival (PFS), and the pooled results indicated no association between them (P>0.05). VDR expression is a prognostic indicator in digestive system tumours and may also be used as a reference for vitamin D supplementation. Detection of VDR expression not only helps to evaluate prognosis but also to formulate more precise treatment plans for patients with digestive system tumours.

Prognostic value of the combined preoperative plasma fibrinogen and systemic inflammatory indexes in ESCC patients.

The prognostic indexes based on the combination of preoperative fibrinogen and systemic inflammatory indexes may have greater predictive value in esophageal squamous cell carcinoma (ESCC). It was found that the predictive ability of F-NLR was more valuable than other systemic inflammatory indexes. The preoperative F-NLR score was closely related to the TNM stage, and could be used as an important independent prognostic index for patients with ESCC. Then the nomogram model constructed by F-NLR and TNM stage had higher prognostic ability than that of AJCC stage for ESCC patients. Preoperative F-NLR is a new independent prognostic index and a potential marker for treatment response monitoring in patients with ESCC.

IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models.

Claudin 18.2 (CLDN18.2)-targeting chimeric antigen receptor (CAR)-modified T cells are one of the few cell therapies currently producing an impressive therapeutic effect in treating solid tumors; however, their long-term therapeutic efficacy is not satisfactory with a short duration of response. Transgenic expression of interleukin (IL)-15 has been reported to promote T-cell expansion, survival, and function and enhance the antitumor activity of engineered T cells in vitro and in vivo. Therefore, this study aimed to explore whether IL-15 modification would increase the antitumor activity of CLDN18.2-targeting CAR-modified T (CAR-T) cells in immunocompetent murine tumor models. CLDN18.2-specific CAR-T cells with (H9 CAR-IL15) or without transgenic IL-15 expression (H9 CAR) were generated by retroviral transduction of mouse splenic T cells. In vitro, compared with H9 CAR T cells, H9 CAR-IL15 T cells exhibited better expansion and viability in the absence of antigen stimulation, with a less differentiated and T-cell exhausted phenotype; although IL-15 modification did not affect the production of effector cytokines and cytotoxic activity in the short-term killing assay, it moderately improved the in vitro recursive killing activity of CAR-T cells against CLDN18.2-expressing tumor cells. In vivo, H9 CAR T cells showed no antitumor activity against CLDN18.2-expressing pancreatic tumors in immunocompetent mice without lymphodepleting pretreatment; however, H9 CAR-IL15 T cells produced significant tumor-suppressive effects. Furthermore, H9 CAR-IL15 T cells exhibited greater in vivo expansion and tumor infiltration when combined with lymphodepleting preconditioning, resulting in superior antitumor activity in two murine tumor models and a survival advantage in one tumor model. We further demonstrated that recurrent tumors following H9 CAR-IL15 T-cell therapy downregulated CLDN18.2 expression, suggesting immune escape through the selection of antigen-negative cells under persistent CAR-T-cell immune pressure. In conclusion, our findings provide preclinical evidence supporting the clinical evaluation of IL-15-expressing CLDN18.2 CAR-T cells in patients with CLDN18.2-positive tumors.

Comparing prognostic value of preoperative platelet indexes in patients with resectable gastric cancer.

The ratio of mean platelet volume (MPV) to count (PC) (MPV/PC) has been applied in the diagnosis and prognosis of various malignancies. However, the prognostic value of MPV/PC in gastric cancer has not been studied yet. This study aims to explore the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), combined neutrophil-platelet score (CNPS), systemic immune-inflammation index (SII) and MPV/PC in patients with resectable gastric cancer. In this study, the medical records of patients with gastric cancer in two centers were retrospectively analyzed. Kaplan-Meier and log-rank were tests applied to analyze the survival differences of patients with various inflammation indexes. A nomogram prognostic model was established to predict the 3- and 5-year survival rate of patients with resectable gastric cancer. In the two cohorts, Kaplan-Meier analysis that the postoperative survival time of gastric cancer patients with low MPV/PC, high NLR, high PLR and high SII was significantly shorter than that of patients with high MPV/PC, low NLR, low PLR or low SII. Compared with NLR, PLR, SII and CNPS, MPV/PC was more accurate in determining the prognosis of patients with gastric cancer than other indexes, and multivariate analysis confirmed that MPV/PC was an independent prognostic factor for patients with resectable gastric cancer. The nomogram model established based on tumor size, TNM stage and MPV/PC was more accurate than TNM stage in predicting the 3- and 5-year survival rate of patients with resectable gastric cancer. Preoperative MPV/PC is a new independent prognostic index and a potential marker for treatment response monitoring in patients with resectable gastric cancer. The nomogram model for postoperative prognosis of gastric cancer established based on MPV/PC, tumor size and TNM stage is helpful for developing more accurate and timely individualized therapeutic regimens.

Dynamic Changes in the Systemic Inflammation Response Index Predict the Outcome of Resectable Gastric Cancer Patients.

The systemic inflammation response index (SIRI) has been revealed to be closely related to the prognosis of a variety of tumors. Whether the dynamic change in SIRI before and after surgery can be used to judge the prognosis of patients after radical gastrectomy has not yet been studied. In this study, the predictive ability of preoperative SIRI and changes in SIRI before and after surgery for the survival rate of gastric cancer patients was evaluated in two independent cohorts. It was found that SIRI was closely related to TNM staging. The higher the TNM stage, the higher the proportion of patients with a high SIRI. However, SIRI was not related to any other clinicopathological parameters. Kaplan-Meier survival analysis showed that a high SIRI was associated with poor prognosis in gastric cancer patients in the original cohort and in the validation cohort. SIRI, NLR, PLR, and MLR could be used to judge the prognosis of patients with operable gastric cancer. However, multivariate analysis suggested that only SIRI was an independent prognostic factor for patients with operable gastric cancer. In addition, the change in SIRI at 4 to 6 weeks after surgery compared with SIRI before surgery was closely related to the survival of gastric cancer patients. Compared with the unchanged group (absolute variation <50%), gastric cancer patients with a SIRI increase >50% had a worse OS, while patients with a SIRI decrease >50% had a better prognosis. In conclusion, SIRI can be used as a reliable index to evaluate the prognosis of patients with operable gastric cancer, and the dynamic change in SIRI before and after surgery is significantly related to the prognosis of patients with gastric cancer.

Prognostic Role of Squamous Cell Carcinoma Antigen in Cervical Cancer: A Meta-analysis.

OBJECTIVE: To systematically evaluate the significance of squamous cell carcinoma antigen (SCC-Ag) in the prognosis of cervical cancer. METHODS: Literature from Pubmed, Embase, and Cochrane Library was retrieved to collect all English literature on the correlation between SCC-Ag and cervical cancer prognosis, and the quality of literature collected was assessed based on evaluation criteria. The heterogeneity, sensitivity, and specificity were detected using the StataSE12.0 software, and the correlation between SCC-Ag and cervical cancer prognosis as the effect variables was assessed using the hazard ratio (HR) and 95% confidence interval (CI). Moreover, the forest map and funnel plot were drawn. RESULTS: A total of 17 articles meeting the inclusion criteria were selected. The high expression of SCC-Ag was significantly correlated with the poor prognosis of cervical cancer (HR = 2.22, 95% CI = 1.38 - 3.57, P = 0.002). The disease-free survival (DFS) was higher in low SCC-Ag expression patients than in high SCC-Ag expression patients (HR = 2.17, 95% CI = 1.84 - 2.57, P < 0.001). The progression-free survival (PFS) was inferior in patients with a high SCC-Ag expression (HR = 2.70, 95% CI = 1.11 - 6.53, P = 0.028). CONCLUSION: SCC-Ag is an important prognostic factor for cervical cancer, and its high expression is significantly correlated with a poor prognosis of the disease.

Nomogram Based on Systemic Immune-Inflammation Index to Predict Overall Survival in Gastric Cancer Patients.

BACKGROUND: The systemic immune-inflammation index (SII), based on peripheral lymphocytes, neutrophils, and platelet count, has been used as a prognostic marker for several tumors. However, use of the SII has not been reported for gastric cancer. METHODS: We evaluated the prognostic value of the SII in primary and validation cohorts. We also established an effective prognostic nomogram for gastric cancer based on R language. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C index) and a calibration curve and were compared with TNM classifications. RESULTS: The Kaplan-Meier survival analysis results showed that the high SII was associated with poor prognosis of gastric cancer patients in the primary and validation cohorts. SII proved to be related to tumor location, histological grade, tumor size, TNM stage, and perineural infiltration in patients with gastric cancer and was an independent prognostic factor for patients with gastric cancer. SII has a better predictive ability than other existing prognostic indexes based on inflammation, such as NLR, PLR, and MLR. The nomogram established can accurately predict the 3- and 5-year survival rates of patients with gastric cancer after operation, and its accuracy is significantly higher than that of the 8th edition of the AJCC staging system. CONCLUSION: SII can independently predict the overall survival of patients with gastric cancer after operation, which is superior to the existing systemic inflammatory indexes. The prognostic nomogram based on SII is a reliable model for predicting the postoperative survival of patients with gastric cancer.

Development and validation of nomogram based on lncRNA ZFAS1 for predicting survival in lymph node-negative esophageal squamous cell carcinoma patients.

BACKGROUND: There is increasing evidence of a relationship between long non-coding RNA (lncRNA) and cancer. This study aimed to examine the prognostic value of the lncRNA ZFAS1 in esophageal squamous cell carcinoma (ESCC). RESULTS: The results showed that ZFAS1 expression was significantly higher in ESCC tissues compared with the corresponding adjacent normal tissues (P < 0.001). ESCC patients with high ZFAS1 expression had a poor overall survival (OS). Histological grade, T stage and ZFAS1 expression were integrated to develop the nomogram. The nomogram showed a significantly better prediction of OS for patients with lymph node-negative ESCC. The ROC curve also showed higher specificity and sensitivity for predicting 3- and 5-year ESCC patient survival compared with the AJCC staging system. The decision curve analysis also indicated a greater potential for the nomogram in clinical application compared with the AJCC staging system. Importantly, our findings were supported by a validation cohort. MATERIALS AND METHODS: We retrospectively investigated 398 lymph node-negative ESCC patients. Data from the primary cohort (n = 246) were used to develop a multivariate nomogram. The nomogram was internally validated for discrimination and calibration with bootstrap samples and was externally validated with an independent patient cohort (n = 152). CONCLUSIONS: Our proposed nomogram, which integrates clinicopathological factors and ZFAS1 expression, can accurately predict the prognosis of lymph node-negative ESCC patients without preoperative chemoradiotherapy.