The Prognostic and Drug-targeting Value of Lymphoid Enhancer-binding Factor-1 in Hepatocellular Carcinoma.

BACKGROUND: Lymphoid Enhancer-Binding Factor-1 (LEF1) was previously reported to contribute to a variety of malignancies, including Hepatocellular Carcinoma (HCC). However, its role in HCC is poorly understood. OBJECTIVES: To explore the role of LEF1 in HCC, including its prognostic and drug-targeting value. METHODS: The LEF1 expression and patient characteristics were investigated. The associations between clinical characteristics and LEF1 were analyzed using both univariate and multivariate logistic regression. Cox regression and Kaplan-Meier curves were used to explore the clinicopathological factors related to overall survival in patients with HCC. A nomogram to predict the survival rate was constructed and validated. The Kyoto Encyclopedia of Genes and Genomes database (KEGG) was used to explore the function of LEF1. Gene Set Enrichment Analysis (GSEA) was also performed using The Cancer Genome Atlas dataset. Furthermore, compounds that may have the potential to be targeted drugs in the treatment of LEF1-overexpressing HCC were identified using the Comparative Toxicogenomics Database (CTD), patents about these drugs in HCC were also reviewed through Worldwide Espacenet® and Patentscope®. RESULTS: Increased expression of LEF1 was significantly associated with high histological grade of HCC (odds ratio (OR) = 2.521 for grade (G) 2 vs. G1, OR = 2.550 for G3 vs. G1, OR = 7.081 for G4 vs. G1, all P < 0.05). A Kaplan-Meier survival curve showed that HCC patients with LEF1 overexpression had a poor prognosis compared with those with normal LEF1 expression (P = 0.025). Multivariate Cox regression analysis revealed that LEF1 is an independent prognostic factor for the overall survival of patients with HCC (Hazard Ratio (HR) = 1.095; P = 0.04). The constructed nomogram to predict the survival rate produced a statistically significant prediction (area under the curve (AUC) = 86.68). In addition, Gene Ontology (GO) and KEGG analysis of genes co-expressed with the protein showed that LEF1 was associated with transcriptional regulation. GSEA suggested that the cell cycle, the WNT signaling pathway, and the NOTCH signaling pathway may be the key pathways regulated by LEF1 in HCC. Furthermore, the Comparative Toxicogenomics Database (CTD) identified nine compounds that may have the potential to be targeted drugs in the treatment of LEF1-overexpressing HCC. Patent reviews suggested that these drugs may show some efficacy in HCC, but whether these drugs interact with LEF1 and improve the prognosis for patients with HCC remains to be explored. CONCLUSION: LEF1 is a latent prognostic molecular biomarker of HCC. The cell cycle, and WNT and NOTCH signaling pathways are regulated by LEF1 in HCC. LEF1 could be a potential drug target for HCC.

Value of Cytokine Expression in Early Diagnosis and Prognosis of Tumor Metastasis.

Objective: To investigate the association of the plasma level of cytokines and blood routine indexes with clinical characteristics in patients with cancer. Methods: We analyzed plasma samples derived from 134 cancer patients. Interleukins (IL) 1ß, 2, 4, 5, 6, 8, 10, 12p70, 17, IFN-γ, IFN-α, and TNF-α, and blood routine indexes were measured. The associations of the levels of cytokine and blood routine indexes with demographic and clinical characteristics of cancer patients were analyzed. Partial least-squares discriminant analysis was employed to identify cancer metastasis using these plasma cytokine metrics as input. We compared the predictive effectiveness of numeric machine learning algorithms using these indexes and showed a promising model implemented with random forest. Results: Plasma levels of IL-6 and IL-8 in cancer patients with metastases were higher than those without metastases (P < 0.05). Cancer patients without metastases had significantly higher levels of plasma IL-12p70 and percentage of lymphocytes as compared with those with metastases (P < 0.05). Our random forest model showed the highest prediction performance (upper quantile AUC, 0.885) among the six machine learning algorithms we evaluated. Conclusion: Our findings suggest that plasma levels of IL-6, IL-8, and IL-12p70 and the percentage of lymphocytes could predict the recurrence, metastasis, and progression of cancer. Our findings will provide guidance for tumor monitoring and treatment.

A case study of combined neoadjuvant chemotherapy and neoadjuvant immunotherapy in resectable locally advanced esophageal cancer.

BACKGROUND: The prognosis of patients under existing neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy requires improvement. Whereas programmed cell death 1 (PD-1) inhibitors have shown promising response in advanced esophageal cancer, they have not been used in the perioperative treatment of resectable locally advanced esophageal cancer. Whether immunotherapy can be incorporated into neoadjuvant therapy has became a challenging question for researchers. CASE PRESENTATION: We present a case of a 65-year-old male who had a history of progressive dysphagia for approximately 1 month. He underwent pertinent studies including computed tomography (CT)，gastroscopy，and pathological biopsy resulting in a diagnosis of medium-low differentiated squamous carcinoma of the thoracic segment of the esophagus (cT2N2M0 stage III). After 4 cycles of neoadjuvant chemotherapy combined with immunotherapy, gastroscopy showed the lesion in the esophagus was no longer present. Subsequently, the patient received thoracoscopic radical resection of esophageal cancer and achieved a pathological complete response (pCR) in postoperative pathological evaluation. During the whole treatment, no adverse effect was recorded and to date no evidence of recurrence has been recorded. CONCLUSION: Our report suggest that neoadjuvant chemotherapy combined with immunotherapy not only improve the R0 resection and pCR rate in patients with resectable locally advanced esophageal cancer, but also the adverse effects are within the control range. However, the selection of therapeutic strategy, predictors of response to treatment, and interval time between neoadjuvant treatment and surgery still await more reliable evidence-based studies with large prospective samples.

Patient-Generated Subjective Global Assessment (PG-SGA) predicts length of hospital stay in lung adenocarcinoma patients.

The prevalence of malnutrition is high among oncology patients in Northern China. Malnutrition is related to the longer hospital stay, and it can be used to predict the prognostic outcome of patients. This work focused on investigating the relationship of nutritional condition with the length of hospital stay (LOS) in Northern Chinese patients with lung adenocarcinoma (LUAD). The Patient-Generated Subjective Global Assessment (PG-SGA), Nutritional Risk Screening 2002 (NRS 2002) score, recent weight loss and BMI were assessed in a probabilistic sample of 389 LUAD patients without epidermal growth factor receptor (EGFR) mutations. This study collected the demographic and clinical features of patients in a prospective manner. Then, we examined the association of nutritional status with LOS among the population developing LUAD. According to the PG-SGA, 63 (16·3 %), 174 (44·7 %) and 78 (20·1 %) patients were at risk for undernutrition, moderate undernutrition and severe undernutrition, respectively. Nutritional risk was found in 141 (36·2 %) patients based on the NRS 2002. The average LOS for tumour patients in Northern China was 12·5 d. At admission, a risk of undernutrition or undernutrition according to the PG-SGA (P < 0·001), NRS 2002 (P < 0·001) and latest weight loss (P < 0·001) predicted the longer LOS. LOS was related to nutritional status and hospitalisation expenses (P < 0·001). LUAD patients who stayed in the ICU had a poorer nutritional status and a longer LOS (P < 0·001). In Northern Chinese patients with LUAD, a risk for undernutrition evaluated by the PG-SGA, the NRS 2002 and recent weight loss, but not BMI, could predict a longer LOS.

Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis.

BACKGROUND: It remains unknown which is the most effective regimen among the available therapies for advanced well-differentiated neuroendocrine tumors (NETs). We performed a network meta-analysis to address this important issue. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR), or odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Included in the meta-analysis were 21 eligible articles reporting 15 RCTs with a total of 2922 patients randomized to receive 11 treatments. Peptide receptor radionuclide therapy (PRRT) showed significant PFS advantage over somatostatin analogs (SSA) (HR = 0.21, 95% CI: 0.11-0.41), everolimus (HR = 0.25, 95% CI: 0.11-0.53), sunitinib (HR = 0.29, 95% CI: 0.10-0.82), everolimus+SSA (HR = 0.26, 95% CI: 0.12-0.54), and everolimus+bevacizumab (HR = 0.31, 95% CI: 0.11-0.82). OS findings were not significantly different between treatments. In terms of treatment rankings of PFS, PRRT had the highest probability (96%) of being the most effective treatment, followed by SSA+bevacizumab (86%) and SSA+interferon-α (IFN-α) (78%). As for toxicity, risk of SAEs was similar between the three treatments. Based on the benefit-risk ratio, PRRT, SSA+bevacizumab, and SSA+IFN-α seemed to be the best, second-, and third-best treatment, respectively. CONCLUSIONS: PRRT is likely to be the most preferable treatment for patients with advanced well-differentiated NETs. SSA+bevacizumab and SSA+IFN-α also seem to be more effective regimens with limited risk of SAEs.

The role of postoperative radiation therapy for completely resected stage III thymoma and effect of higher heart radiation dose on risk of cardiovascular disease: A retrospective cohort study.

OBJECTIVES: This study aimed to assess the efficacy of radiation therapy (RT) in patients with completely resected stage III thymoma and evaluate the relationship between higher heart dose and risk of cardiovascular disease (CVD). PATIENTS AND METHODS: A total of 130 consecutive patients with Masaoka stage III thymoma were retrospectively reviewed from January 2003 to December 2013. Of these, 99 underwent complete tumor resection [74 received postoperative radiation therapy (S + R) and 25 received surgery alone (S alone)] and 31 patients underwent RT alone (16 due to inoperable tumors and 15 due to high surgical risk or patient refusal; R alone). Three-dimensional conformal RT/intensity-modulated RT was used for patients receiving RT. RESULTS: The median follow-up for all patients was 70 months. The 5- and 8-year overall survival (OS) rates were 95.6% and 93.9% for S + R, 84.0% and 67.2% for S alone, and 73.3% and 73.3% for R alone (excluding patients with inoperable tumors), respectively (P = 0.004). A trend of improved disease-specific survival (DSS) was also observed in the S + R group compared with the other two groups. CVD was the main nonmalignant cause of death (3/6, 50%). The median time of CVD diagnosis was 101 months after treatment. The mean heart dose was an independent risk factor for CVD. CONCLUSIONS: Postoperative RT after complete resection improved the survival compared with surgery alone and RT alone for patients with stage III thymoma. A higher heart dose was related to increased risk of CVD in long-term survivors.