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@#Objective To construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. Results A total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.
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@#Objective To investigate the biological characteristics and clinical significance of cuproptosis-related genes in lung adenocarcinoma (LUAD) based on the multi-omics data from The Cancer Genome Atlas. Methods The cuproptosis-related genes were obtained from a study published in Science in March 2022. The whole genome data were used to reveal the mutation spectrum and copy number variation landscape of cuproptosis-related genes in LUAD and analyze its effects on transcriptome expression. Cuproptosis-related genes were annotated using Metascape analysis to further understand the pathways or functions in which these genes were involved. Subsequent univariate Cox analysis and Kaplan-Meier methods determined the prognosis of these genes in LUAD patients, and CellMiner analysis were used to identify those potential anticancer drugs for potentially targeting cuproptosis-related genes. Results Cuproptosis-related genes were less frequently mutated in LUAD, and the effect of gene mutations on transcriptomic expression may depend on the type of mutation. Gene copy number variation was an important factor resulting in the disordered expression of cuproptosis-related genes. The 16 cuproptosis-related genes were mainly involved in glyoxylate metabolism and glycine degradation, copper ion entry, proteolitidylation, cellular amino acid catabolism process, oxidative stress response, etc. Among them, 6 genes (DLD, FDX1, DLAT, DLST, PDHA1, CDKN2A) were prognostic risk genes in LUAD. The CellMiner analysis suggested that 13 drugs were associated with 7 cuproptosis-related genes and they might be potential anticancer drugs for potentially targeting cuproptosis. Conclusion This study reveals the biological characteristics and clinical significance of cuproptosis-related genes in LUAD, and provides some reference and theoretical basis for the subsequent research of cuproptosis in cancer.
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Objective To understand preliminaryly the epidemiological trend of lung cancer in recent years by retrospective analysis of 2 403 cases of lung cancer in Zhongnan Hospital of Wuhan University from 2013 to 2017.Methods The clinical data of patients with primary bronchogenic cancer diagnosed in Zhongnan Hospital of Wuhan University from 2013 to 2017 were collected.The clinical data such as gender,age,history of tobacco and alcohol,operation,pathological type,clinical stage and epidermal growth factor receptor (EGFR) gene mutation were analyzed statistically.Results A total of 2 403 cases of lung cancer were collected,including 1 766 males and 637 females.There was no significant difference in gender ratio between male and female in five years (x2 =8.481,P =0.075).There were 2 398 cases with age information,the male-to-female ratios of lung cancer patients aged less than 40,40-49,50-59,60-69,70-79,80 and over were 0.9 ∶ 1.0,1.4 ∶ 1.0,2.4 ∶ 1.0,3.6 ∶ 1.0,3.4 ∶ 1.0 and 3.3 ∶ 1.0 respectively,and the difference was statistically significant (x2 =59.004,P ＜ 0.001).The composition difference of adenocarcinoma was not statistically significant in five years (x2 =2.165,P =0.705).There was no statistically significant difference in the composition ratio of squamous cell carcinoma (x2 =4.788,P =0.310).Adenocarcinoma accounted for 43.15％ (762/1 766) and 81.95％ (522/637) of the pathological types of male and female patients respectively,and the difference was statistically significant (P ＜ 0.001).Squamous cell carcinoma accounted for 39.01％ (689/1 766) and 7.28％ (47/637) respectively,and the difference was statistically significant (P ＜ 0.001).The proportion of squamous cell carcinoma in smoking patients was 42.99％ (583/1 356),which was significantly higher than that in non-smoking patients (14.61％,153/1 047);the proportion of squamous cell carcinoma in drinking patients was 40.56％ (277/683),which was higher than that in nondrinking patients (26.69％,459/1 720),and the differences were statistically significant (both P ＜ 0.001).A total of 1 252 patients underwent surgery,accounting for 52.10％ (1 252/2 403) of the total cases.The surgical rate of small cell carcinoma was 21.72％ (48/221),and that of non-small cell carcinoma was 55.18％ (1 204/2 182).In five years,the surgical rates of lung cancer patients were 55.11％ (221/401),51.53％ (252/489),58.23％ (244/419),53.18％ (276/519) and 45.04％ (259/575) respectively,and there was significant difference in the proportion of surgical and non-surgical patients in each year (x2 =19.553,P =0.001).A total of 483 patients were tested for E GFR mutation,the EGFR mutation rate was 58.8％ (251/ 427) in adenocarcinoma patients and 15.6％ (5/32) in squamous cell carcinoma patients.Among lung cancer patients aged less than 40,40-49,50-59,60-69,70-79,80 and over,the proportions of adenocarcinoma were 76.74％ (33/43),62.39％ (136/218),57.73％ (381/660),47.95％ (455/949),52.22％ (235/450) and 52.56％ (41/78) respectively,and the difference was statistically significant (x2 =33.078,P ＜ 0.001);the proportions of squamous cell carcinoma were 9.30％ (4/43),21.56％ (47/218),28.03 ％ (185/660),34.14％ (324/949),32.44％ (146/450) and 35.90％ (28/78) respectively,and the difference was statistically significant (x2 =26.977,P ＜ 0.001).The difference of composition ratio of TNM staging was statistically significant in five years (x2 =21.003,P =0.034).Conclusion There has been no significant change of male-to-female ratio in patients with lung cancer in the past five years.With the increase of age,the male-to-female ratio increases first and then decreases.The proportion of adenocarcinoma and squamous cell carcinoma has not increased or decreased significantly in the past five years.Adenocarcinoma and squamous cell carcinoma are both common in male lung cancer patients,while the pathological type of female patients is mainly adenocarcinoma.Squamous cell carcinoma is highly prevalent in smokers and drinkers.The surgical rate of squamous cell carcinoma is higher than that of adenocarcinoma,and the surgical rate of non-small cell lung cancer is higher than that of small cell lung cancer.The EGFR mutation rate is higher in adenocarcinoma.With the increase of age,the proportion of adenocarcinoma in all pathological types tends to decrease,while that of squamous cell carcinoma tends to increase.The patients' TNM staging has a downward trend,and the operation rate decreases slightly.