Corrigendum: ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway.

[This corrects the article DOI: 10.3389/fonc.2022.887068.].

Development and validation of a nomogram based on multiple preoperative immunoinflammatory indexes for survival prediction in patients with stage IA-IB endometrial cancer.

OBJECTIVES: To evaluate the preoperative systemic immune-inflammation index (SII), advanced lung cancer inflammation index (ALI), neutrophil to lymphocyte ratio (NLR), and prognostic nutritional index (PNI) capacity to predict the prognosis of stage IA-IB endometrial carcinoma (EC) patients after operation, and establish a nomogram model to guide clinical practice. METHODS: A total of 387 patients with EC (R0 resection, stage IA-IB) were assessed. Clinical information and the SII, NLR, ALI, and PNI values were obtained. The low and high ratio groups were separated using the receiver operating characteristic curve (ROC). Pearson's χ2-test or Fisher's exact test was used to determine their relationship with clinical variables. To determine the independent prognostic factors, Cox regression was utilized to do the univariate and multivariate survival analyses. The Kaplan-Meier method was used to draw the survival curve in our survival analysis. Depending upon the independent prognostic factors, the nomogram for Overall survival (OS) and Disease-free survival (DFS) nomogram was developed, and its discrimination ability was validated by the consistency index (C-index) and calibration curve. RESULTS: Cox regression analysis revealed that FIGO staging, Ki-67 expression level, PNI, and ALI are independent prognostic factors for both OS and DFS. Then a novel predictive nomogram was developed, and its C-index value for OS and DFS was 0.829 and 0.814, respectively. The calibration curves demonstrated consistency amid the predicted prognosis using the developed nomogram and the actual observed outcomes. CONCLUSIONS: The ALI and PNI could serve as readily available prognostic indicators for OS and DFS prediction in stage IA-IB EC patients. The nomogram developed owned superior power for OS and DFS prediction in stage IA-IB EC patients, and it would assist clinical oncologists in accurately predicting the individual's OS and DFS.

Extended adjuvant temozolomide in newly diagnosed glioblastoma: A single-center retrospective study.

Objective: To investigate whether extending adjuvant temozolomide (TMZ) improved the prognosis of newly diagnosed glioblastoma (GBM) patients with different mutation statuses of O6-methylguanine DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 (IDH1), p53 and different expression level of Ki67. Methods: This study was a retrospective cohort study that postoperative patients with newly diagnosed GBM who did not progress after receiving radiotherapy with concomitant and 6 cycles of adjuvant TMZ were enrolled in control group, and those received more than 6 cycles of adjuvant TMZ were incorporated in extended group. Patients were stratified by MGMT expression, IDH1 mutation, p53 mutation and expression level of Ki67. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Result: A total of 93 postoperative patients with newly diagnosed GBM were included in this study, 40 and 53 cases were included in control group and extended group, respectively. On the whole, extended adjuvant TMZ chemotherapy significantly prolonged OS and PFS of patients with newly diagnosed GBM [median OS (mOS): 29.00 months vs. 16.70 months, P < 0.001; median PFS (mPFS): 13.80 months vs. 9.60 months, P = 0.002]. The results of subgroup analysis showed that patients with methylated MGMT in extended group had significantly longer OS and PFS than those in control group; patients with IDH1 mutation benefited more from extended adjuvant TMZ chemotherapy than those with wild-type IDH1; there was no significant difference in the effect of extended TMZ chemotherapy on OS between GBM patients with wild-type p53 and those with mutant p53; compared with GBM patients with lower expression of Ki67, extended adjuvant TMZ treatment dramatically improved the OS and PFS of those with higher expression of Ki67. Conclusion: The therapeutic schedule of extended adjuvant TMZ significantly prolonged OS and PFS of patients with newly diagnosed GBM regardless of p53 mutation status, and patients with different MGMT methylation, IDH1 mutation and Ki67 expression level benefited differently from extended adjuvant TMZ chemotherapy.

ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway.

Pancreatic adenocarcinoma (PAAD) is one of the most aggressive digestive system tumors in the world, with a low early diagnosis rate and a high mortality. Integrin beta 5 (ITGB5) is demonstrated to be a potent tumor promoter in several carcinomas. However, it is unknown whether ITGB5 participates in the occurrence and development of PAAD. In this study, we confirmed a high expression of ITGB5 in PAAD and its role in promoting invasiveness and transitivity in PAAD. Besides, the knockdown of ITGB5 increased cell sensitivity to radiation by promoting DNA damage repair and the MEK/ERK signaling pathway. Collectively, these results show that ITGB5 plays an essential role in pancreatic cancer growth and survival.

Different classes of antibiotics exhibit disparate negative impacts on the therapeutic efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

It has been reported that antibiotics (ATBs) have adverse effect on the efficacy of treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Since different classes of ATBs have different antibacterial spectrum, we aimed to study whether all ATBs had similar or different negative effects on the clinical outcomes of ICIs in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who received ICIs were included in this retrospective study and grouped by the class of ATBs they had used around the ICIs treatment time. The overall survival (OS) and the progression free survival (PFS) of patients among these groups were compared using Kaplan-Meier method and Cox proportional hazards model. A total of 148 eligible patients were enrolled, and 80 patients used ATBs. The results indicated that quinolones had no significant negative consequence on the clinical outcomes, while ß-lactams significantly shortened the OS and PFS of patients. Furthermore, patients exposed to the combination of ß-lactams and quinolones suffered the worst OS and PFS. Moreover, the subgroup analysis of ß-lactams revealed that only penicillins, but not carbapenems and cephalosporins, markedly reduced both OS and PFS. In addition to the class of ATBs used, the time frame of ATBs used also affected the clinical outcomes of ICIs therapy. Patients receiving ATBs within 60 days prior to and 30 days after the initiation of ICI treatment had significantly shorter OS and PFS compared with those who did not use ATBs. This study demonstrated that different classes of ATBs had disparate negative impacts on the clinical outcomes, and the use of ß-lactams, especially penicillins, should be avoided in advanced NSCLC patients who are receiving or scheduled to receive ICIs within 60 days.

Systematic pan-cancer analysis identifies RBM39 as an immunological and prognostic biomarker.

RNA-binding Motif Protein39 (RBM39) is identified as a splicing factor and transcription coactivator. Despite mounting evidence that RBM39 plays a critical role in the development of specific malignancies, no systematic pan-cancer investigation of RBM39 has been conducted. As a result, we set out to investigate RBM39's prognostic significance and putative immunological activities in 33 different cancers. Based on TCGA and CCLE, GTEx, cBioportal and HPA, we used a series of bioinformatics approaches to explore the potential oncogenic role of RBM39, including analysis of the expression of the pan-cancer species RBM39, the prognostic relationship between RBM39 expression and overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI), the relationship between RBM39 expression and clinical phenotype, analysis of the relationship between RBM39 expression and tumour mutational burden (TMB), microsatellite instability (MSI), DNA methylation and immune cell infiltration. Our results showed that RBM39 is overexpressed in most cancers. RBM39 was positively or negatively correlated with the prognosis of different tumours. RBM39 expression was associated with TMB and MSI in 9 and 12 cancer types. In addition, RBM39 expression was associated with DNA methylation in almost all tumours. There are eight tumours were screened for further study, including BRCA, COAD, HNSC, LIHC, LUSC, SKCM, STAD, UCEC. In the screed tumours, RBM39 was found to be negatively correlated with the infiltration of most immune cells. In addition, the correlation with RBM39 expression varied by immune cell subtype. Based on RBM39's role in tumorigenesis and tumour immunity, we suggest it can serve as a surrogate prognostic marker.

A novel preoperative MRI-based radiomics nomogram outperforms traditional models for prognostic prediction in pancreatic ductal adenocarcinoma.

To develop an efficient prognostic model based on preoperative magnetic resonance imaging (MRI) radiomics for patients with pancreatic ductal adenocarcinoma (PDAC), the preoperative MRI data of PDAC patients in two independent centers (defined as development cohort and validation cohort, respectively) were collected retrospectively, and the radiomics features of tumors were then extracted. Based on the optimal radiomics features which were significantly related to overall survival (OS) and progression-free survival (PFS), the score of radiomics signature (Rad-score) was calculated, and its predictive efficiency was evaluated according to the area under receiver operator characteristic curve (AUC). Subsequently, the clinical-radiomics nomogram which incorporated the Rad-score and clinical parameters was developed, and its discrimination, consistency and application value were tested by calibration curve, concordance index (C-index) and decision curve analysis (DCA). Moreover, the predictive value of the clinical-radiomics nomogram was compared with traditional prognostic models. A total of 196 eligible PDAC patients were enrolled in this study. The AUC value of Rad-score for OS and PFS in development cohort was 0.724 and 0.781, respectively, and the value of Rad-score was negatively correlated with PDAC's prognosis. Moreover, the developed clinical-radiomics nomogram showed great consistency with the C-index for OS and PFS in development cohort was 0.814 and 0.767, respectively. In addition, the DCA demonstrated that the developed nomogram displayed better clinical predictive usefulness than traditional prognostic models. We concluded that the preoperative MRI-based radiomics signature was significantly related to the poor prognosis of PDAC patients, and the developed clinical-radiomics nomogram showed better predictive ability, it might be used for individualized prognostic assessment of preoperative patients with PDAC.

The role of necroptosis in disease and treatment.

Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases.

Association of glycosylated hemoglobin and outcomes in patients with COVID-19 and pre-existing type 2 diabetes: A protocol for systematic review and meta-analysis.

BACKGROUND: The impact of glycosylated hemoglobin on mortality in patients with coronavirus disease 2019 (COVID-19) and type 2 diabetes (T2D) remains uncertain. In this study, we aim to assess the effect of pre-hospital blood glucose regulation on patients with COVID-19 and pre-existing T2D. METHODS: All randomized controlled trials (RCTs) and cohort studies of association of glycosylated hemoglobin and outcomes in patients with COVID-19 and T2D will be included in this review. PubMed, Embase, and CNKI will be searched for relevant literature, up to August 20, 2020 in English and Chinese language. Two reviewers will select trials independently for inclusion and assess trial quality. Two pairs of authors will independently extract information for each included trials. Primary outcomes are death and composite adverse outcomes: the number of participants who died or remained severely disabled. Revman 5.3 will be used for heterogeneity assessment, data synthesis, subgroup analysis, sensitivity analysisa and generating funnel-plots. RESULTS: We will provide practical results about the association of glycosylated hemoglobin and outcomes in patients with COVID-19 and T2D. CONCLUSION: The stronger evidence about the association of glycosylated hemoglobin and outcomes in patients with COVID-19 and T2D will be provided for clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020200574. ETHICS AND DISSEMINATION: There is no need for ethical approval, and the review will be reported in a peer-reviewed journal.

A comparison of sotagliflozin therapy for diabetes mellitus between week 24 with week 52 : A protocol for mixed treatment comparisons meta-analysis.

BACKGROUND: According to the centers for disease control and prevention, 14% of American adults have diabetes - 10% know it, and more than 4% go undiagnosed. Sotagliflozin is a new type of diabetes drug This study is to compare the efficacy of Sotagliflozin therapy for Diabetes Mellitus (DM) between week 24 with week 52. METHODS AND ANALYSIS: Through to October 2019, Web of Science, PubMed Database, Cochrane Library, EMBASE, Clinical Trials and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA therapy for DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software. We will provide practical and targeted results assessing the lost efficacy of SOTA therapy for DM from week 24 to week 52, to provide reference for clinicians. ETHICS AND DISSEMINATION: The stronger evidence about the lost efficacy of SOTA for DM from week 24 to week 52 will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133027. STRENGTHS AND LIMITATIONS OF THIS STUDY: Whether the efficacy of SOTA could last for a long time is still inconclusive, high quality research is still lacking, and this study attempts to explore this issue; The efficacy of SOTA at different times will be compared by direct comparisons and indirect comparisons, this can lead to more accurate and reliable results; The quality of the included literatures are uneven, and some data might be estimated by calculation, which may affect the quality of this study.

Effect of lipid metabolism disorder on liver function in patients with malignant tumors after chemotherapy: a case-control study.

BACKGROUND: This study aims to investigate the effect of lipid metabolism disorder on liver function in patients with malignant tumors after chemotherapy. METHOD: A total of 428 patients with malignant tumors with normal liver function in our hospital between May 2013 to June 2018 were divided into an observation group (lipid metabolism disorder, n = 265) and control group (normal lipid metabolism, n = 163). The lipid metabolism levels and liver damage of the two groups were compared before and after chemotherapy. RESULTS: No significant differences in age, gender, body mass index, tumor types, history of surgery, levels of alanine aminotransferase (ALT; an indicator of liver function), and chemotherapy regimen were observed between the two groups. However, the observation group showed increased levels of total cholesterol (P = 0.000), triglycerides (P = 0.000), and low-density lipoprotein (P = 0.01), as well as decreased levels of high-density lipoprotein (P = 0.000) before chemotherapy compared with the control group. Furthermore, patients with lipid metabolism disorders were more likely to develop abnormal liver function after chemotherapy. Moreover, mixed lipid metabolism disorder was more likely to cause severe liver damage after chemotherapy. Additionally, the number of patients with lipid metabolism disorders after chemotherapy (n = 367) was significantly increased compared with before chemotherapy (n = 265) (P < 0.01), indicating that chemotherapy might induce or aggravate an abnormal lipid metabolism. CONCLUSIONS: After receiving chemotherapy, patients with malignant tumors presenting lipid metabolism disorders are more prone to liver damage and lipid metabolism disorders than patients with a normal lipid metabolism.