LC Patients Research Articles

Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Lastly, MAGEB2 is significantly associated with immune cell infiltration (CD8+ T cells particularly, IHC staining confirmed that as the protein expression of MAGEB2 increased, the protein level of CD8 (representing tumor-infiltrating CD8 + T cells) decreased in vitro), immunomodulators (knockdown or overexpression of MAGEB2 on LC cell lines can significantly affect the chemokine/cytokine secretion in vitro), and immunogenicity(TMB) in LC, which hints that MAGEB2 is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for LC patients.

Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis.

BackgroundLiver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis.ResultsThe expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC.ConclusionsFor LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.

P017 Transcriptional characterization of lymphocytic colitis and comparison to collagenous colitis

Abstract Background Lymphocytic colitis (LC) is an inflammatory disease of the large intestine that causes chronic, watery, non-bloody diarrhoea. LC is characterized by infiltration of lymphocytes in the colonic mucosa. To better understand LC pathophysiology on a molecular level, we performed genome-wide RNA sequencing (RNA-seq) analysis on LC mucosal samples. Methods We collected colonic biopsies from healthy controls (Hc), and LC patients with active disease. Collagenous colitis (CC) samples were included as a separate control. Total RNA was isolated from biopsies for bulk RNA-seq. Whole-genome expression data were analysed by principal component analysis (PCA), differential gene expression (DGE), and gene-set variation analysis (GSVA) using R statistical software. Benjamini-Hochberg FDR was used to adjust p values, considering <0.05 as statistically significant. Gene-set enrichment analysis (GSEA) was performed using GSEA software and visualized in Cytoscape. Results PCA of all samples identified 2 principal components that explained 65% of the transcriptional variation and separated sample groups into distinct clusters of gene expression. Subsequent analysis revealed differential expression of 5045 genes in patients with active LC compared to Hc, which were mainly involved in DNA and telomere repair, in ubiquitinylation and proteasomal degradation, response to viruses and interleukin (IL)-12 signalling according to GSEA. Compared to CC samples, we identified 384 differentially expressed genes (DEGs) with LC. Pathway analysis displayed an enrichment in cell adhesion and proliferation genes in LC, whereas DEGs related to microbial response, collagen and wound healing processes, chemotaxis, and epithelial biology (e.g. ion channels, epithelial cell proliferation) were enriched for CC samples. Estimations of infiltrating immune cells performed by GSVA indicated a possible role for professional antigen-presenting cells (i.e. macrophages and inactive dendritic cells) as well as T regulatory cells in LC pathogenesis. Conclusion LC is a transcriptionally homogeneous disease that can be characterised by increased expression of cell adhesion and proliferation-related genes. Furthermore, our analyses confirm an elevated immune response in LC, particularly involving macrophages, dendritic and T regulatory cells. Comparison of LC and CC gene expression additionally supports that these diseases are pathobiologically distinct.

ENDOTHELIUM DYSFUNCTION IN PATIENTS WITH LIVER CIRRHOSIS

Aim: To assess endothelial dysfunction in patients with liver cirrhosis. Material and methods: The study involved 95 patients with alcoholic liver cirrhosis. The data were subjected to analysis of variance involving the calculation of arithmetic mean value and variance (М±m), estimating the values validity according to Student’s t-test and measuring Pearson correlation coefficient for binary variables. Results: The brachial artery diameter was 0.4±0.02 mm narrower, with its blood velocity flow being 25.8±3.4 cm/s slower in the mean, in the patients with liver cirrhosis with signs of hepatic encephalopathy as compared to the control group. The maximum EDV values were recorded in the patients in Group I (7.5±1.9 %), while Group III patients displayed the lowest EDV value (5.6±1.9 %). The LC patients were found to exhibit a significant increase in the concentration of ET-1 up to 1.14±0.07 fmol/ml as opposed to 0.34±0.05 fmol/ml in the control group (р<0.01), an increase in the level of VWF by 139.4±24,8 % as compared to the control group (р<0.01) and D-dimer by a factor of 6.8. Conclusions: The patients with liver cirrhosis were found to have endothelial damage, namely the dysfunction of the vasoregulating activity of vascular wall against the background of portal hypertension. Changes in the vasoactive BAS values are indicative of the damage to the vascular endothelium in LC patients with signs of HE. A steady and gradual increase or decrease in the levels of ЕТ-1, VWF, АТ ІІІ, and D-dimer may suggest the progressive character of ED in the LC patients.

Clinical Course of Liver Cirrhosis in Torch-infected Patients and the Possibility of Correction Using “Polyana Kvasova” Mineral Water

Aim: To investigate the peculiarities of clinical and laboratory changes in liver cirrhosis in TORCH-infected patients and their dynamics against the background of complex therapy with the use of Polyana Kvasova mineral water (MW). Materials and Methods: 64 patients with alcohol-related LC were examined. The study was carried out in two stages. At the 1st stage, the examined patients with LC were divided into two groups depending on the presence or absence of TORCH infections to determine the characteristics of the clinical course of LC in these patients. Group I included patients with LC (n=30), who were not diagnosed with TORCH infection, and group II included patients with LC who tested positive for antibodies to infections of the TORCH group (n=34). The data of patients of group II were divided into two subgroups, depending on the treatment performed. Patients of subgroup IIA (n=16) received only basic therapy (BT), and patients of subgroup IIB (n=18) were additionally prescribed 100 ml of warm, still carbonated bicarbonate-sodium Polyana Kvasova mineral water (MW), 15-20 minutes before meals 6 times a day. The duration of the treatment and observation of patients at the second stage of the study was 1 month. Results: In patients with LC of group II, signs of jaundice, pain and dyspeptic syndromes were statistically significantly more often detected - p<0.05. In group II of patients with LC, a more pronounced, statistically significant increase in the indicators of cholestatic syndrome. A more significant reduction in the manifestations of dyspeptic and pain syndrome, as well as the severity of jaundice, was observed in LC patients of the IIB subgroup who, in addition to BT, were prescribed Polyana Kvasova MW. A significant decrease in laboratory markers of cholestatic syndrome was established (TBIL level by 20.0±0.6 mmol/L; ALP by 84.0±1.8 IU/L, GGT by 48.7±1.5 U/L) in the subgroup of patients, who in addition to BT were prescribed MW. Conclusions: 1. In TORCH-infected patients, alcohol-related liver cirrhosis is more often detected at the stage of subcompensation (class C according to Child-Pugh) and is clinically detected by signs of dyspeptic and pain syndromes, as well as laboratory manifestations of cholestatic syndrome and jaundice syndrome. 2. The use of Polyana Kvasova MW as part of the complex therapy of patients with alcohol-related liver cirrhosis in combination with TORCH infection is a pathogenetically based and safe method for reducing the severity of dyspeptic and pain syndromes, as well as clinical and laboratory signs of jaundice in these patients.

Lung Cancer Scenario of NICRH: A Cross Sectional View

Introduction: Lung cancer alone and in coalition can deactivate life-wheel. But a very little attention had been paid to address the riddle. This effort is to candle the light on the lung cancer disease.
 Objective: This study was conducted to delineate the sociodemographic factors and clinical conditions of lung cancer patients. To determine some associations of SD variables and clinical conditions.
 Methods & Materials: This cross-sectional study was conducted in NICRH from July 2017 to June 2018 among 167 LC patients. Data were collected by interview using semi-structured questionnaire and reviewing of check list. Data were checked thoroughly, edited, coded, categorized, cleaned and analyzed using software (SPSS version 23).
 Results: This study revealed that mean age of the patients was 56.16 ± SD 9.88. Among which 80.2% were male and 19.8% female. Majority had primary 51.1% education Secondary were 26.4%. Regarding occupation, farmer were 37.1%, businessmen were 20.4% and homemaker were 15.6. The mean income was Tk. 17163 ± SD Tk. 10587. Most had nuclear family 89.2%. Rural inhabitants were 61.1%. In describing cancer type, 81.5% had NSCC and 16.8% had SCC. Regarding clinical condition, 70% had poor, 7.8% had average and 22.2% had severe clinical condition. The residential areas are significantly (χ2, p < .05) associated with clinical conditions. Staging of lung cancer is significantly (χ2, p < .05) associated with clinical conditions.
 Conclusion: Socioeconomic factors like age, family income, education, residential condition may affect clinical condition.
 AKMMC J 2022; 13(1) : 37-41

Patterns of cardiac involvement in patients with long COVID syndrome using cardiovascular magnetic resonance

BackgroundLong COVID (LC) is an increasingly recognized late complication of COVID-19 infection. Cardiovascular involvement has also been implicated, however, the type and extent of the underlying cardiovascular injury remains unknown.PurposeTo evaluate the association between ongoing symptoms and findings with cardiovascular magnetic resonance (CMR) in consecutive patients recently recovered from COVID-19 illness.MethodsProspective observational cohort study of patients recently recovered from COVID-19 illness and no previously known cardiovascular disease were included between April 2020 and April 2021. Demographic characteristics, cardiac blood markers, and CMR imaging a minimum of 4 weeks from the diagnosis were obtained.ResultsOf the 389 included patients, 192 (49%) were male, the mean (±standard deviation) age was 44 (±13) years and 61 (16%) required hospitalization during the acute illness. The median (IQR) time interval between COVID-19 diagnosis and CMR was 94 (71–165) days. 298 (77%) of patients continued to experience ongoing cardiovascular symptoms (long COVID, LC), including dyspnea, palpitations, atypical chest pain and fatigue at the time of CMR at least 4 weeks after the infection. In most patients, the symptoms were only effort related 137 (46%), whereas in 98 (33%) the symptoms affected the activities of daily life; 10 (3%) had severe and debilitating symptoms at rest. Compared to those with no LC (NLC, n=91), LC patients were more commonly hospitalized, had significantly higher native T1, native T2, and showed pericardial enhancement and effusion (Figure 1). There were no differences in cardiac biomarkers, left ventricular (LV) and right ventricular ejection fraction and mass. Proportionally, men and women were similarly affected (n=144 (73%) vs. n=157 (80%), p=0.18). Previous hospitalization was associated with hypertension and ongoing detectable troponin. LC status was associated with previous hospitalization and CMR findings of raised native T1 and native T2, and in females also pericardial enhancement. Severity of symptoms were associated with increased native T1 and T2 and decreased end-diastolic volume, whereas cardiac function showed no significant difference.ConclusionsIn this cohort of patients recently recovered from COVID-19 infection, ongoing cardiovascular symptoms were common. The LC status was related to previous hospitalization and CMR imaging findings of myopericardial inflammation. The extent and type of cardiovascular findings was associated with the severity of symptoms. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.Funding AcknowledgementType of funding sources: Foundation. Main funding source(s): The German Heart Foundation (Deutsche Herzstiftung) and Bayer AG, Leverkusen, Germany Figure 1

The Association Between PNPLA2 Methylation in Peripheral Blood and Early-Stage Lung Cancer in a Case-Control Study.

PurposeLung cancer (LC) brings great burden to the society worldwide. Exploring novel biomarkers in vitro for the early detection of LC would be of great importance.Patients and MethodsWe measured DNA methylation levels of 21 CpG sites within Patatin-like phospholipase domain containing 2 (PNPLA2) gene in the peripheral blood of 168 early-stage LC cases (94.0% LC at stage I) and 187 age- and gender-matched cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression adjusted for covariates. Non-parametric tests were applied for the comparisons of stratified groups.ResultsHypomethylation of PNPLA2_CpG_8,10 and hypermethylation of PNPLA2_CpG_9 were correlated to the early-stage LC with the ORs of 1.44 (95% CI: 1.06–1.96, P = 0.018) and 0.82 (95% CI: 0.69–0.98, P = 0.029), respectively. The associations were still significant for the very early-stage LC patients (stage I). Further gender- and age-stratified analyses indicated that the association between hypomethylation of PNPLA2_CpG_8,10 and LC existed only in females and in subjects younger than 55 years. In addition, the association between LC and hypermethylation of PNPLA2_CpG_6 and PNPLA2_CpG_9 was also observed in the younger population.ConclusionTaken together, our study has proved the hypothesis that the altered methylation in the peripheral blood may be correlated with the burden of cancer at an early stage. Here, we find a novel association between blood-based aberrant PNPLA2 methylation and LC at a very early stage and particularly for women at a younger age.

Specific Gut Microbiome and Serum Metabolome Changes in Lung Cancer Patients.

BackgroundLung cancer (LC) is one of the most aggressive, prevalent and fatal malignancies. Gut microbes and their associated metabolites are thought to cause and modulate LC development, albeit influenced by the host genetic make-up and environment. Herein, we identified and classified gut microbiota and serum metabolites associated with LC.MethodsStool samples were collected from 41 LC patients and 40 healthy volunteers. The gut microbiota was analyzed using 16S rRNA gene sequencing. Serum samples were collected from the same LC patients (n=30) and healthy volunteers (n=30) and serum metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). Microbiome and metabolome data were analyzed separately and integrated for combined analysis using various bioinformatics methods.ResultsSerum metabolomics uncovered 870 metabolites regulated in 76 metabolic pathways in both groups. Microbial diversity analyses identified 15967 operational taxonomic units (OTUs) in groups. Of these, the abundance of 232 OTUs was significantly different between HC and LC groups. Also, serum levels of glycerophospholipids (LysoPE 18:3, LysoPC 14:0, LysoPC 18:3), Imidazopyrimidines (Hypoxanthine), AcylGlcADG 66:18; AcylGlcADG (22:6/22:6/22:6) and Acylcarnitine 11:0 were substantially different between HC and LC groups. Combined analysis correlated LC-associated microbes with metabolites, such as Erysipelotrichaceae_UCG_003, Clostridium and Synergistes with glycerophospholipids.ConclusionsThere is an intricate relationship between gut microbiome and levels of several metabolites such as glycerophospholipids and imidazopyrimidines. Microbial-associated metabolites are potential diagnostic biomarkers and therapeutic targets for LC.

Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients.

Identification of host genetic factors influencing the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection may help to refine patients' selection to benefit from specific preventative measures and/or adapted screening policies. Thus, this study aimed to investigate the association of MTHFR c.677C > T and c.1298A > C in addition to TYMS 3'-UTR 6-bp ins/del polymorphisms with the susceptibility to HCV-related HCC in an Egyptian population. Polymerase chain reaction-restriction fragment length polymorphism was performed to genotype the polymorphisms in 194 HCV-infected patients subdivided into liver cirrhotic (LC, n = 104) and HCC (n = 90) patients as well as 100 healthy subjects. In healthy controls, the MTHFR c.677C > T polymorphism under the homozygous and recessive models (p = 0.005) and the c.1298A > C polymorphism under all the tested genetic models (p-values range from < 0.001 to 0.007) were associated with an increased risk of HCC. In LC patients, the MTHFR c.677C > T polymorphism under the homozygous, dominant, and recessive models (p-values range from 0.001 to 0.007), as well as MTHFR c.1298A > C under the homozygous model only (p = 0.014), increased the susceptibility to HCC. The C/C and T/C haplotypes of MTHFR c.677C > T and MTHFR c.1298A > C polymorphisms were contributed to an increased risk of healthy subjects to develop HCC (p-values range from < 0.001 to 0.015), while only the T/C haplotype was associated with the progression of HCC in LC patients (p = 0.001). In conclusion, MTHFR c.677C > T and c.1298A > C in addition to their haplotypes may contribute to the development of HCV-related HCC in an Egyptian population. These findings may aid in the early diagnosis and management of HCC.

The role of metformin on lung cancer survival: the first systematic review and meta-analysis of observational studies and randomized clinical trials.

To assess the effects of metformin use onlung cancer (LC) survival according to summarized results from observational studies (OBs) and randomized clinical trials (RCTs). We systematically searched electronic databases and, to our knowledge, for the first time, RCTs were included in a systematic review and meta-analysis about the role of metformin onLC survival. We carried out meta-analyses separately for OBs and RCTs. Analyses for overall survival (OS) concerning OBs were stratified by studies with and without time-dependent approach. Subgroup analyses were adopted for OBs to identify the sources of heterogeneity. Included studies were assessed for quality. We identified ten OBs and four RCTs. For OBs, metformin use was associated with improved OS for LC patients. Only two studies used time-dependent approach in which a higher ratio was found when compared to the non-use of the time-dependent analysis in eight studies. OBs were classified as high quality but the risk of bias was "unclear" in eight OBs due to absence of the time-dependent analysis. For RCTs, metformin use was not beneficial for OS and neither for progression-free survival. Heterogeneous quality was found among RCTs. Sources of bias that could alter significantly the results or raise doubts were identified in RCTs. Time-dependent analysis should be considered an appropriate strategy for OBs focused on the metformin use for LC patients' survival, and further studies applying this approach are required. More well-designed RCTs are needed to provide consistent results for the association between metformin use and LC survival.

Synchronous bone metastasis in lung cancer: retrospective study of a single center of 15,716 patients from Tianjin, China

BackgroundThis study aimed to describe the incidence, clinical characteristics, and prognosis of lung cancer patients with synchronous bone metastasis (SBM) and to analyze the prognostic factors of the lung cancer patients with SBM.MethodsA total of 15,716 lung cancer patients who were diagnosed between 2009 to 2018 in the Tianjin Medical University Cancer Institute and Hospital were retrospectively reviewed. Among them, patients with SBM were checked. Both the demographic and clinical characteristics were included as follows: age, gender, marital status, history of smoking, alcohol consumption, family history of tumor, Karnofsky score, lymph node metastasis, histological type. Besides, laboratory data such as alkaline phosphatase, lactate dehydrogenase, carcinoembryonic antigen, squamous cell carcinoma antigen, cytokeratin-19 fragment, and neuron specific enolase were also included. The log-rank test and multivariate Cox regression analysis were employed to reveal the potential prognostic predictors. A further analysis using the Kaplan–Meier was employed to demonstrate the difference on the prognosis of LC patients between adenocarcinoma and non-adenocarcinoma.ResultsAmong the included patients, 2738 patients (17.42%) were diagnosed with SBM. A total of 938 patients (34.3%) with SBM were successfully followed and the median survival was 11.53 months (95%CI: 10.57–12.49 months), and the 1-, 2-, and 5-year overall survival rate was 51, 17, and 8%, respectively. Multivariable Cox regression results showed history of smoking and high level of NSE were associated with the poor prognosis, while adenocarcinoma histological type was associated with better survival.ConclusionThe prevalence of SBM in lung cancer is relatively high with poor survival. The lung cancer patients with SBM showed diverse prognosis. Among all the pathological types, the division of adenocarcinoma suggested different prognosis of the lung cancer patients with SBM. The present study emphasized the importance of pathological diagnosis on prognostic determinants in lung cancer patients with SBM.

Dignity therapy in Mexican lung cancer patients with emotional distress: Impact on psychological symptoms and quality of life

To analyze the effect of DT on anxiety, depression, hopelessness, emotional distress, dignity-related distress, and quality of life (QoL) in a group of Mexican patients with stage IV LC undergoing active medical treatment with baseline emotional distress. In this preliminary pretest-posttest study, patients received three sessions of DT and were evaluated with the HADS, Distress Thermometer, Patient Dignity Inventory, single-item questions, and QLQ-30. In total, 24 out of 29 patients completed the intervention. Statistically significant improvements were found in anxiety, depression, emotional distress, hopelessness, and dignity-related distress with large effect sizes. Patients reported that DT helped them, increased their meaning and purpose in life, their sense of dignity, and their will to live, while it decreased their suffering. No changes were found in QoL. DT was well accepted and effective in improving the emotional symptoms of LC patients with distress that were undergoing medical treatment. Although more research is warranted to confirm these results, this suggests that DT can be used in the context of Latin-American patients.

Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression

The inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.

Ferroptosis-related genes for predicting prognosis of patients with laryngeal squamous cell carcinoma.

Previous studies reported that ferroptosis-related genes can regulate the process of tumor cell changes by regulating iron metabolism. However, the prognostic value of ferroptosis-related genes in LC remains to be further elucidated. Ferroptosis-related gene expression profiles of coexisting ferroptosis-related genes were extracted from both cohorts (TCGA and GSE27020) for eligible analysis. LASSO Cox regression was utilized to build an optimum ferroptosis-related prognostic model. Kaplan-Meier curve was performed by log-rank test, and time-dependent ROC curve was constructed to evaluate the predictive power of this signature in both cohorts. GO and KEGG enrichment analysis was used to investigate the potential mechanism of differential enrichment signal pathways. 112 LC patients from the TCGA cohort and 108 LC patients with clinical information from the GEO cohorts were eventually included in the study. Three ferroptosis-related genes were identified as an independent risk factor to establish the prognostic risk score. Kaplan-Meier curve represented that patients with high-risk group favors with worse OS than their low-risk group (P = 0.04). The good performance of the gene signature for predicting OS was evaluated by area under the curve (AUC) of time-dependent ROC curves achieved 0.74 at 3years, and 0.70 at 5years. Similar performance has been proved in the external validation cohort. GO and KEGG enrichment analysis have been performed to explore the signaling pathways and underlying mechanisms were significantly active in LC patients. In summary, our study developed a ferroptosis-related model that could be an effective biomarker to predict the prognosis of laryngeal cancer.

Effect and Mechanism of Transthyretin over-Expression on Proliferation and Cell Cycle of Lung Cancer A549 Cells.

Background:The effects of transthyretin (TTR) over-expression on the proliferation and cell cycle of non-small cell lung cancer (NSCLC) A549 cells and its possible mechanism were verified.Methods:A total of 196 LC patients and 20 healthy controls were enrolled at Tianjin Hospital, Tianjin, China between Apr 2017 and Oct 2017. The serum TTR content was detected by ELISA. Through lentiviral transfection method, NSCLC cells were divided into non-transfected group (group A), negative control group (group B) transfected with empty vector and experimental group (group C) transfected with TTR over-expression. Cell proliferation was detected by CCK-8 method, TTR mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and TTR protein expression was tested by Western blot (WB). Cell cycle was detected by flow cytometry, Wnt3a/β-catenin protein expression was detected by WB, and mRNA expression was detected by RT-qPCR.Results:The serum TTR content in early, middle and late LC group was remarkably lower than that in healthy group (P<0.05). Compared with late stage, TTR content in early and middle stages of LC group was higher, and the difference was statistically marked (P < 0.05). The absorbance value of group C was lower than that of groups A and B, indicating that the cell proliferation activity dramatically decreased, with statistically marked difference (P<0.05). LC A549 cells in group C were obviously blocked in G2M, with statistical significance (P<0.05).Conclusion:TTR over-expression can inhibit the proliferation of NSCLC A549 cells, and the expression is related to Wnt3a/β-catenin pathway. TTR in serum of patients was helpful for diagnosing LC and has certain clinical value.

Management and Prognosis of Interstitial Lung Disease With Lung Cancer (ILD-LC): A Real-World Cohort From Three Medical Centers in China

Background and ObjectiveInterstitial lung disease with lung cancer (ILD-LC) is rare and its management has not been fully described. This study aimed to investigate the management and prognosis of ILD-LC patients in China.MethodsThe present analysis is a retrospective real-world cohort study. Clinical data of ILD-LC patients were obtained from 3 hospitals in China. The overall survival (OS) of patients was analyzed. Univariate and multivariate regression analyses were performed.ResultsOne hundred eighty-four ILD-LC patients included were biased toward male (85.3%), smokers (75.5%), idiopathic pulmonary fibrosis (IPF) (58.2%) patients with comorbidities (67.9%) and ECOG-PS score of 1 (65.2%). Most patients were advanced peripheral non-small cell lung cancer. The initial anti-cancer regimen for ILD-LC is mainly chemotherapy, and patients with early-stage LC prefer surgery. In the anti-cancer cohort, the number of ILD-LC patients who underwent the 2nd and 3rd or more anti-cancer regimens were 78 (55.7%) and 32 (22.8%), respectively. In the non-anticancer cohort, the median OS was 3.5 months. In the early-stage cohort, the median OS was 14.2 months in the systematic therapy group; however, the median OS was not reached in the surgery group. In the advanced-stage cohort with systematic therapy, the median OS was 7.2 months. Interstitial pneumonia (IIP) and anti-angiogenesis were associated with OS in the univariate analysis, whereas anti-angiogenesis was an independent protective factor for advanced LC with ILD.ConclusionPatients with ILD-LC have very poor prognosis. Appropriate anti-tumor treatment can prolong the survival time of patients who can tolerate it. Targeted therapy and immunotherapy are alternative treatments for LC patients with mild ILD. For ILD patients with advanced LC, antiangiogenic regimens significantly improve the prognosis of the disease.

Clinicopathologic characteristics of laryngeal chondrosarcoma: An analysis of the National Cancer Database

ObjectivesLaryngeal Chondrosarcoma (LC) is a rare malignancy with limited studies documenting its clinicopathologic characteristics and treatment options. This study reports demographic and clinical determinants of outcomes for this rare tumor. MethodsThe National Cancer Database (NCDB) was queried for cases of LC reported from 2004–2016. 274 cases that met inclusion criteria were analyzed for demographic and clinicopathologic characteristics. Kaplan-Meier (KM) and Cox proportional hazard analyses were conducted to identify variables that impacted the overall survival of these patients. ResultsLC was found to be more common in males (74.8%). The mean age of patients was 61.8 years and 92.3% of the patients were white. 91.3% of patients were treated with only surgical resection, most commonly: partial laryngectomy (31.6%), total laryngectomy (25.7%), and local resection (22.4%). 98.8% of patients had no evidence of nodal disease and 99.6% of patients did not have distant metastasis at presentation. KM analysis revealed a 5-year overall survival (5YOS) of 89.0%. Age, insurance status, facility type, and surgery type were significant predictors of 5YOS (p<0.05). On Cox Proportional Hazard analysis, private insurance significantly improved survival (HR 0.21; p = 0.048) while increasing age was a poor prognostic indicator (HR 1.10; p = 0.004). ConclusionThe majority of LC patients present with no nodal involvement or distant metastasis at diagnosis, and overall this tumor has a favorable prognosis. Increasing age was found to be a poor prognostic factor while private insurance status was associated with improved survival.

Bim's Effect on the Expression of miR-423-3p in Promoting Primary Hepatic Cancer (PHC) and Role of miR-423-3p in PHC Proliferation and Invasion.

In this study, we analyzed the miR-423-3p expression in primary hepatic cancer (PHC), its effect on cell proliferation, and migration and explored Bcl-2-interacting mediator effect on the role of miR-423-3p in promoting liver cancer. The miR-423-3p expression levels in LC tissues and adjacent non-tumor tissues were compared, and the relationship between miR-423-3p and clinical pathological characteristics of patients was analyzed. These levels in peripheral blood of LC patients and healthy volunteers were compared, and the diagnostic value of miR-423-3p in LC was analyzed. The miR-423-3p and BCL-2-interacting mediators of cell death (Bim) expression in LC cells SMMC-7721 and Huh-7 were analyzed. The changes of cell proliferation, invasion, and apoptosis level were evaluated. Furthermore, the association and regulatory relationship between miR-423-3p and Bim were evaluated by dual luciferase report. The miR-423-3p expression level in LC increased, indicating miR-423-3p could be a diagnostic marker for LC. miR-423-3p expression was relatively low in patients with low TNM stage (I-II) and LC with serum AFP level ≤ 20μg/L, related to the 5-year survival rate of LC patients. The 5-year survival rate of patients with low miR-423-3p expression was dramatically higher than that of those with high miR-423-3p expression. The miR-423-3p can promote proliferation and migration of LC cells and inhibit apoptosis, Bim can inhibit their growth and metastasis, and miR-423-3p can also regulate Bim expression. The miR-423-3p expression level in LC increased and could inhibit Bim to promote the proliferation and invasion of LC cells and inhibit apoptosis.

Insulin Growth Factor-1 as a Predictor for the Progression of Hepatic Disease in Chronic Hepatitis B Virus Infection

Background &amp; Aims: The aim of this study was to assess IGF-1 in chronic liver diseases associated with HBV infection and describe the impact of liver status on IGF-1 variables. Methods: This cohort study included 348 subjects and conducted between December 2018 and December 2019 at El-Sahel Teaching Hospital, Cairo, Egypt. Subjects were divided into 4 groups: group I included HBV positive hepatocellular carcinoma patients “HCC” (n= 87), group II included HBV positive patients with liver cirrhosis “LC” (n = 87), group III included chronic hepatitis B (CHB) patients with neither HCC nor cirrhosis “CHB” (n = 87) and group IV of healthy volunteers as controls (n = 87). Serum IGF-1 was measured quantitatively using a commercially available enzyme immunoassay. Results: Serum levels of IGF-1 were measured in each of the 4 groups. The comparison showed marked differences in IGF1-related measures. It was found to be significantly reduced in HCC patients (32.08 ± 9.2 ng/ml), LC patients (50.6±14.1ng/ml) and CHB patients (61.4±14.3 ng/ml) in comparison to healthy subjects (140.4±49.9 ng/ml). The reduction of IGF-1 levels was also statistically significant between both HCC and LC patients and CHB patients also between HCC and LC patients. Conclusion: Serum IGF-1 levels are significantly reduced with the progression of hepatic disease in HBV patients and it may be a promising serological marker alone or in association with others for prediction of development of liver cirrhosis and HCC in chronic HBV patients.