Integrative bioinformatics approaches to establish potential prognostic immune-related genes signature and drugs in the non-small cell lung cancer microenvironment.

Introduction: Research has revealed that the tumor microenvironment (TME) is associated with the progression of malignancy. The combination of meaningful prognostic biomarkers related to the TME is expected to be a reliable direction for improving the diagnosis and treatment of non-small cell lung cancer (NSCLC). Method and Result: Therefore, to better understand the connection between the TME and survival outcomes of NSCLC, we used the "DESeq2" R package to mine the differentially expressed genes (DEGs) of two groups of NSCLC samples according to the optimal cutoff value of the immune score through the ESTIMATE algorithm. A total of 978 up-DEGs and 828 down-DEGs were eventually identified. A fifteen-gene prognostic signature was established via LASSO and Cox regression analysis and further divided the patients into two risk sets. The survival outcome of high-risk patients was significantly worse than that of low-risk patients in both the TCGA and two external validation sets (p-value < 0.05). The gene signature showed high predictive accuracy in TCGA (1-year area under the time-dependent ROC curve (AUC) = 0.722, 2-year AUC = 0.708, 3-year AUC = 0.686). The nomogram comprised of the risk score and related clinicopathological information was constructed, and calibration plots and ROC curves were applied, KEGG and GSEA analyses showed that the epithelial-mesenchymal transition (EMT) pathway, E2F target pathway and immune-associated pathway were mainly involved in the high-risk group. Further somatic mutation and immune analyses were conducted to compare the differences between the two groups. Drug sensitivity provides a potential treatment basis for clinical treatment. Finally, EREG and ADH1C were selected as the key prognostic genes of the two overlapping results from PPI and multiple Cox analyses. They were verified by comparing the mRNA expression in cell lines and protein expression in the HPA database, and clinical validation further confirmed the effectiveness of key genes. Conclusion: In conclusion, we obtained an immune-related fifteen-gene prognostic signature and potential mechanism and sensitive drugs underling the prognosis model, which may provide accurate prognosis prediction and available strategies for NSCLC.

Death anxiety and its relationship with family function and meaning in life in patients with advanced cancer-A cross-sectional survey in China.

Objective: This study explores the factors influencing death anxiety in patients with advanced cancer, and to investigate the role of family function on death anxiety, and the correlation between meaning in life and death anxiety. Methods: Patients with advanced cancer who were hospitalized in three institutions from November 2020 to May 2021 were recruited in this cross-sectional study. The Chinese version of the Death and Dying Distress Scale, Meaning in Life Scale For Advanced Cancer Patients and Family APGAR Index were used to assess death anxiety, meaning in life and family function. Pain symptoms were evaluated by the Numeric Rating Scale. Karnofsky Performance Status, patients' socio-demographic and clinical variables were also recorded. Statistical analyses were performed using IBM SPSS Statistics for Windows (version 26.0). Multivariate regression analysis was performed to examine the correlations of social-demographic and clinical variables with family function and death anxiety. Results: Three hundred and twenty-eight patients with advanced cancer were included in this study. The results showed that 12.2% of patients experienced moderate to severe death anxiety. Meaning in Life Scale For Advanced Cancer Patients (acceptance of death, controlling one's life), types of institution (oncology department of tertiary hospitals), self-perceived economic burden (extreme), Karnofsky Performance Status score, age, and medical insurance status (self-paid, inter-provincial medical insurance) were identified as associated factors of death anxiety (R 2 â€‹= â€‹0.335, F â€‹= â€‹20.072, P â€‹< â€‹0.001). Patients with good family function scores had significantly low level of death anxiety in univariate analysis (F â€‹= â€‹5.892, P â€‹= â€‹0.003). Multivariate analysis revealed no significant association between family function and death anxiety. Conclusions: Our results demonstrated that the oncology department of a tertiary hospital, extremely high of self-perceived economic burden, self-pay, and inter-provincial medical insurance might be associated with higher death anxiety in patients with advanced cancer. Lower level death anxiety was associated with higher level acceptance of death, a greater sense of life control, better physical performance, and older age. Further confirmation about the association between family function and death anxiety in patients with advanced cancer is warranted in the future.

Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer.

Abnormal lipid metabolism often occurs under hypoxic microenvironment, which is an important energy supplement for cancer cell proliferation and metastasis. We aimed to explore the lipid metabolism characteristics and gene expression features of pancreatic ductal adenocarcinoma (PDAC) related to hypoxia and identify biomarkers for molecular classification based on hypoxic lipid metabolism that are evaluable for PDAC prognosis and therapy. The multiple datasets were analyzed integratively, including corresponding clinical information of samples. PDAC possesses a distinct metabolic profile and oxygen level compared with normal pancreatic tissues, according to the bioinformatics methods. In addition, a study on untargeted metabolomics using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry(UPLC-MS) revealed lipid metabolites differences affected by oxygen. Analysis of PDAC gene expression profiling in The Cancer Genome Atlas (TCGA) revealed that the sphingolipid process correlates closely with HIF1α. According to the characters of HIF-1 and sphingolipid, samples can be clustered into three subgroups using non-negative matrix factorization clustering. In cluster2, patients had an increased survival time. Relatively high MUC16 mutation arises in cluster2 and may positively influence the cancer survival rates. This study explored the expression pattern of lipid metabolism under hypoxia microenvironment in PDAC. On the basis of metabolic signatures, we identified the prognosis subtypes linking lipid metabolism to hypoxia. The classifications may be conducive to developing personalized treatment programs targeting metabolic profiles.

Hsa-microRNA-370-3p targeting Snail and Twist1 suppresses IL-8/STAT3-driven hepatocellular carcinoma metastasis.

The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa-miR-370-3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL-8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR-370-3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL-8-mediated modification of miR-370-3p. Gain- and loss-of-function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro- and antitumor activities. Interleukin-8 and miR-370-3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL-8 experienced more metastasis and shorter survival. Interleukin-8 induced epithelial-mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA-370-3p interacted with its cognate mRNA within the 3'-UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL-8 protumoral effects on liver cancer cells. Interleukin-8 negatively modulated miR-370-3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR-370-3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR-370-3p and low IL-8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL-8/STAT3/miR-370-3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR-370-3p in HCC metastasis.

Self-perceived burden and influencing factors in patients with cervical cancer administered with radiotherapy.

BACKGROUND: Cervical cancer is the fourth commonest malignancy in women around the world. It represents the second most commonly diagnosed cancer in South East Asian women, and an important cancer death cause in women of developing nations. Data collected in 2018 revealed 5690000 cervical cancer cases worldwide, 85% of which occurred in developing countries. AIM: To assess self-perceived burden (SPB) and related influencing factors in cervical cancer patients undergoing radiotherapy. METHODS: Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University, China between March 2018 and March 2019. The survey was completed using a self-designed general information questionnaire, the SPB scale for cancer patients, and the self-care self-efficacy scale, Strategies Used by People to Promote Health, which were delivered to patients with cervical cancer undergoing radiotherapy. Measurement data are expressed as the mean ± SD. Enumeration data are expressed as frequencies or percentages. Caregivers were the spouse, offspring, and other in 46.4, 40.9, and 12.7%, respectively, and the majority were male (59.1%). As for pathological type, 90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas, respectively. Stage IV disease was found in 12 (10.9%) patients. RESULTS: A total of 115 questionnaires were released, and five patients were excluded for too long evaluation time (n = 2) and the inability to confirm the questionnaire contents (n = 3). Finally, a total of 110 questionnaires were collected. They were aged 31-79 years, with the 40-59 age group being most represented (65.4% of all cases). Most patients were married (91.8%) and an overwhelming number had no religion (92.7%). Total SPB score was 43.13 ± 16.65. SPB was associated with the place of residence, monthly family income, payment method, transfer status, the presence of radiotherapy complications, and the presence of pain (P < 0.05). The SPB and self-care self-efficacy were negatively correlated (P < 0.01). In multivariate analysis, self-care self-efficacy, place of residence, monthly family income, payment method, degree of radiation dermatitis, and radiation proctitis were influencing factors of SPB (P < 0.05). CONCLUSION: Patients with cervical cancer undergoing radiotherapy often have SPB. Self-care self-efficacy scale, place of residence, monthly family income, payment method, and radiation dermatitis and proctitis are factors independently influencing SPB.

A new 7-gene survival score assay for pancreatic cancer patient prognosis prediction.

Gene expression features that are valuable for pancreatic ductal adenocarcinoma (PDAC) prognosis are still largely unknown. We aimed to explore pivotal molecular signatures for PDAC progression and establish an efficient survival score to predict PDAC prognosis. Overall, 163 overlapping genes were identified from three statistical methods, including differentially expressed genes (DEGs), coexpression network analysis (WGCNA), and target genes for miRNAs that were significantly related to PDAC patients' overall survival (OS). Then, according to the optimal value of the cross-validation curve (lambda = 0.031), 7 non-zero coefficients (ARNTL2, DSG3, PTPRR, ANLN, S100A14, ANKRD22, and TSPAN7) were selected to establish a prognostic prediction model of PDAC patients. We further confirmed the expression level of 7 genes using RT-PCR, western blot, and immunohistochemistry staining in PDAC patients' tissues. Our results showed that the ROC curve of the 7-mRNA model indicated good predictive ability for 1- and 2-year OS in three datasets (TCGA: 0.71, 0.69; ICGC: 0.8, 0.74; GEO batch: 0.61, 0.7, respectively). The hazard ratio (HR) of the low-risk group had a similar significant result (TCGA: HR = 0.3723; ICGC: HR = 0.2813; GEO batch: HR = 0.4999; all P < 0.001). Furthermore, Log-rank test results in three cohorts showed that the 7-mRNA assay excellently predicted the prognosis and metastasis, especially in TNM stage I&II subgroups of PDAC. In conclusion, the strong validation of our 7-mRNA signature indicates the promising effectiveness of its clinical application, especially in patients with TNM stages I&II.

Predictive value of intratumour inflammatory cytokine mRNA levels of hepatocellular carcinoma patients and activation of two distinct pathways govern IL-8 induced epithelial-mesenchymal transition in human hepatic cancer cell lines.

Hepatocellular carcinoma (HCC) is always accompanied by persistent inflammation of liver tissues, which is considered to exert protumourigenic effects by promoting cancer growth, progression, and metastasis. However, the tumour-promoting roles and predictive value of intratumoural inflammatory cytokines remain unclear. In the present study, we used database analysis, clinical pathological studies, and in vitro biological experiments on human hepatic cancer cell lines to assess the prognostic potential of the primary tumour cytokine mRNA levels and underlying mechanisms in HCC. First, we assessed the prognostic value of several cytokines from the TCGA database and found that IL-8 is a unique cytokine that is associated with poor overall survival of HCC patients. Then, we collected 87 HCC tumour and adjacent non-tumour specimens from patients and confirmed that patients with low IL-8 expression exhibited less intrahepatic invasion or distant metastasis, a lower recurrence rate and longer overall survival time compared to patients with high IL-8 expression. Wound healing, transwell, and western blotting assay results showed that IL-8 promotes the migration and invasion of Huh-7 and HepG2 cells, and the underlying mechanism is that IL-8 induces the EMT of HCC cells via the IL-8/ERK1/2/SNAI1 and IL-8/STAT3/TWIST1 signalling pathways. These results provide valuable biological IL-8 information which needs to be further investigated in liver cancer target therapy research. Furthermore, the intratumoural cytokine expression at the mRNA level may provide insight into hepatocarcinoma prognosis.