Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.

Associations between interleukin-1 polymorphisms and gastric cancers among three ethnicities

AIM:To investigate the associations between interleukin(IL)-1B and IL-1RN polymorphisms and gastric cancers among the Tibet,Hui and Han ethnicities.METHODS:Genomic DNA was extracted from peripheral blood of 210,205,and 202 healthy volunteers and from 155,158,and 197 gastric cancer patients from the Tibet,Hui,and Han populations,respectively.Polymorphisms in IL-1B and IL-1RN were analyzed by denaturing high-performance liquid chromatography.RESULTS:Carriers of the IL-1B-31 CC genotype had an increased risk of intestinal type gastric cancer [odds ratio(OR) = 2.17,P = 0.037] in the Tibet ethnicity.Carriers of the IL-1B 2/L genotype had an increased risk of both intestinal and diffuse types of gastric cancer(OR = 2.08,2.31,P = 0.007,0.016,respectively) in the Hui ethnicity.In the Han population,carriers of the IL-1B-31 CC,IL-1B-511CT,TT genotypes had increased risk of intestinal type gastric cancer(OR = 2.51,2.74,5.66,P = 0.005,0.002,0.000,respectively).CONCLUSION:IL-1B and IL-RN genotypes may differentially contribute to gastric cancer among the Tibet,Hui,and Han ethnicities in the Qinghai area of China.

Application of rational emotive behavior therapy in patients with colorectal cancer undergoing adjuvant chemotherapy

Objective:This study aimed to explore the effects of our rational emotive behavior therapy(REBT)program on symptoms,anxiety,depression,and sleep state in patients with colorectal cancer(CRC)undergoing chemotherapy.Methods:From October 2020 to May 2021,fifty-six patients with CRC in a hospital in the Hunan Province were randomly divided into an intervention group(n=28)and a control group(n=28).The patients in the intervention group completed a 6-week REBT program based on routine nursing care,including four courses:1)establish a relationship and formulate health files;2)group communications and study symptom management;3)continuously provide health knowledge and strengthen healthy behavior;and 4)review the treatment and summary.The control group maintained routine nursing care.The simplified Chinese version of the Memorial Symptom Assessment Scale Short Form(MSASeSFeSC),the Hospital Anxiety and Depression Scale(HADS),and the Pittsburgh Sleep Quality Index(PSQI)scale were used to investigate and compare the intervention effects of the two groups at baseline(T1,before the intervention),four weeks(T2),and six weeks(T3)after the intervention.Results:The intervention group was significantly improved in symptoms,anxiety,depression,and sleep state,compared with the control group.At T2,MSASeSFeSC(24.43±4.26 vs.28.07±3.91),symptom distress(17.29±4.04 vs.19.39±3.59),symptom frequency(7.14±1.51 vs.8.68±1.42),HADS(13.68±3.38 vs.15.86±3.79),anxiety(3.89±1.85 vs.5.18±2.18),and depression(9.79±2.06 vs.10.68±2.23),showed that the difference between the two groups was statistically significant(P<0.05).At T3,MSASeSFeSC(23.89±3.54 vs.30.14±3.94),symptom distress(17.61±3.52 vs.21.32±3.57),symptom frequency(6.29±1.49 vs.8.82±1.47),HADS(11.82±2.57 vs.16.29±3.13),anxiety(3.21±1.64 vs.5.61±1.77),and depression(8.61±1.52 vs.10.68±1.81),showed that the difference between the two groups was statistically significant(P<0.05).The sleep state of the intervention group was better than the control group at T3,with decreased score of PSQI[4.00(3.00,8.00)vs.9.00(7.00,12.50),Z=-3.706,P<0.001].Conclusion:The 6-week REBT program can effectively improve the symptom,anxiety,depression,and sleep state of patients with CRC undergoing chemotherapy,which could as a care plan for patients with CRC who are repeatedly admitted to the hospital for chemotherapy.

Skin rash caused by EGFR-TKI could be treated successfully by Pien Tze Huang Unguentum Compositum: a case report

Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)plays an important role in cancer therapy.However,EGFR is highly expressed in the skin and gives rise to one of the most concerning issues for the EGFR-TKI treatment,namely skin toxicity.Antibiotics and corticosteroids are usually used to treat the EGFR inhibitor-associated skin rash,with prominent side effects over long-time use.Pien Tze Huang(PZH)Unguentum Compositum is a traditional product for external application which is made of traditional Chinese medicine and oil base.Herein,we reported the case of a 50-year-old man who presented with skin rash on the face,head,and back induced by an EGFR-TKI named erlotinib.By using PZH Unguentum Compositum,we observed that the skin rash was mitigated and eventually disappeared.This case report suggests that PZH Unguentum Compositum may be an effective therapy in treating skin rash caused by EGFR-TKI with fewer side effects.

Effect of microRNA-143-3p-mediated CTNND1 on the biological function of lung cancer cells

Lung cancer poses a serious threat to human life with high incidence and miRNA is an important biomarkerin tumors. This study aimed to explore the effect of miR-143-3p on the biological function of lung cancer cells and theunderlying mechanism. Eighty-seven samples of lung cancer tissues and 81 samples of tumor-adjacent tissues from patients undergoing radical lung cancer surgery in our hospital were collected. The lung cancer cells and lung fibroblastcells (HFL-1) were purchased, and then miR-143-3p-mimics, miR-NC, si-CTNND1, and NC were transfected into A549 and PC-9 cells to establish cell models. MiR-143-3p and CTNND1 expression levels were measured by the qRT-PCR, Bax, Bcl-2, and CTNND1 expression levels by the Western Blot (WB), and cell proliferation, invasion, and apoptosis by the MTT assay, Transwell assay, and flow cytometry. Dual luciferase report assay was used to determinethe relationship between miR-143-3p and CTNND1. In this study, miR-143-3p was lowly expressed in lung cancer and CTNND1 was highly expressed in lung cancer. The overexpression of miR-143-3p inhibited cell proliferation and invasion, promoted cell apoptosis, significantly increased Bax protein expression, and decreased Bcl-2 protein expression. The inhibition of CTNND1 led to opposite biological characteristic in cells. The dual luciferase reporter assay demonstrated that miR-143-3p was a target region of CTNND1. Such results suggest that miR-143-3p can inhibitthe proliferation and invasion of lung cancer cells by regulating the expression of CTNND1 and promote the apoptosisof lung cancer cells, sott is expected to be a potential target for lung cancer.

Roxadustat for treatment of anemia in a cancer patient with endstage renal disease:A case report

BACKGROUNDMost cancer patients are accompanied by anemia, which will be more seriouswhen combined with end-stage renal disease (ESRD). At present, cancer-relatedanemia and renal anemia treatments mainly include erythropoiesis-stimulatingagents (ESAs), iron supplementation, and blood transfusion, but their effects areoften poor with several safety concerns. We have used roxadustat to treat anemiain a cancer patient with ESRD and achieved a successful outcome for the firsttime.CASE SUMMARYA 64-year-old man was diagnosed with right renal cancer (clear cell renal cellcarcinoma). He did not receive surgery or radiotherapy before admission. He wastreated with oral soltan (sunitinib malate) on April 18, 2017. During oral chemotherapy,he had numerous complications, including anemia, hypertension,thyroid hypofunction, skin pigment loss, and renal function deterioration. At last,he progressed to ESRD and began hemodialysis treatment. We initially treated thepatient with high-dose ESAs, iron supplementation, adequate dialysis, and evenblood transfusion, but his anemia did not improve. Roxadustat is a newlydeveloped drug for renal anemia treatment, but not for cancer-related anemia, letalone to treat anemia in cancer patients with ESRD. We prescribed oral roxadustatto the patient. After a period, his hemoglobin gradually increased. He did nothave obvious discomfort symptoms, and his tumor did not progress significantly.CONCLUSIONOral roxadustat could achieve good results in treating anemia in cancer patients with ESRD.

Research Progress on the Effect of Sphingosine Kinase 2 on Glioma

Objective:The purpose of this study is to explore the role of sphingosine kinase 2(SphK2)in the treatment of glioma,which is the most common primary tumor in the central nervous system.Methods:A total of 82 patients were included in this study,with 27 cases in the control group and 55 cases in the glioma group;the expressions of SphK2 and gpl30 in the two groups were compared by immunohistochemical method,and the correlation between the two factors was analyzed.Results:Both SphK2 and gpl30 were upregulated in the glioma group,and the two factors were significantly correlated.Conclusion:The high expression of SphK2 may play an important role in the occurrence,development,and diagnosis of glioma.

C-terminal variants of the P2X7 receptor are associated with prostate cancer progression and bonemetastasis–evidence from clinical and pre-clinical data

Dear Editor Bone is the most common site for metastasis in prostate cancer(PCa),and identifying clinically useful biomarkers to predict the risk of currently incurable bone metastases is a major priority in PCa research.Extracellular adenosine triphosphate(ATP)was shown to be a major biochemical constituent of the tumor microenvironment and regulates the tumor and host interactions by acting at P2 purinergic receptors.Among the P2 receptors,the ion channel P2X purinergic receptor 7(P2X7R)has an unusually long C-terminus containing 200 amino acids,which forms the molecular basis for the unique bi-function of P2X7R promoting cancer cell proliferation or inducing membrane permeabilization and apoptosis,upon activation by a low or high concentration of ATP,respectively.

Clinical observation and therapeutic evaluation of intravenous pump of recombinant human endostatin combined with TP regimen in treating patients with advanced ovarian cancer

Objectives: To observe the curative effects and adverse reactions of recombinant human (rh)-endostatin injection combined with a TP regimen for treating patients with advanced ovarian cancer.Methods: Fifty-four patients with pathologically confirmed ovarian cancer were randomly divided into a combined treatment (intravenous pump of rh-endostatin + TP regimen) group and a control (single chemotherapy) group, twenty-seven patients in each group.All patients were given a conventional CT examination.The level of vascular endothelial growth factor (VEGF), the size of tumor before treatment, after 2 cycles and after 4 cycles of treatment were determined for the comparison of curative effects and adverse reactions.Results: The effective rate was 37.0％ (10/27) and disease control rate was 63.0％ (17/27) in the combined treatment group after 2 cycles of treatment.The effective rate was 25.9％ (7/27) and disease control rate was 63.0％ (17/27) in the control group.The comparison between these two groups showed no significant differences (P ＞ 0.05).The effective rate was 63.0％ (17/27) and disease control rate was 92.6％ (25/27) in the combined treatment group after 4 cycles of treatment.The effective rate was 29.6％ (8/27) and disease control rate was 63.0％ (17/27) in the control group.The effective rate and disease control rate between these two groups after 4 cycles of treatment showed significant differences (P ＜ 0.05).The incidences of cardiovascular toxicity, myelosuppression, sore muscles and joints, alopecia and gastrointestinal reaction was not significantly different between two groups (P ＞ 0.05).Conclusion: The pump delivery of rh-endostatin can down-regulate the expression of VEGF in ovarian cancer and has the better curative effect and slighter adverse reactions.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial

Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.

Genetic alternations and immune characteristics in patients with small cell lung cancer

Dear Editor,As an aggressive and recalcitrant subtype of lung cancer,small cell lung cancer(SCLC)is linked with a dismal prognosis where chemotherapy remains the backbone of treatment.In this disappointing context,immunotherapy has brought hope for patients with SCLC[1].However,data on the genomic and immunological landscape of SCLC are urgently needed to achieve more precise and effective treatment.Here,we conducted a comprehensive analysis of genetic alteration and immune characteristics in a cohort of Chinese patients with SCLC.