Long Non-coding RNA X-Inactive Specific Transcript Promotes Esophageal Squamous Cell Carcinoma Progression via the MicroRNA 34a/Zinc Finger E-box-Binding Homeobox 1 Pathway.

BACKGROUND: The long non-coding RNA X-inactive specific transcript (XIST) plays a crucial role in transcriptional silencing of the X chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-mesenchymal transition (EMT) regulation. AIMS: This study aimed to investigate the impact of XIST on esophageal squamous cell carcinoma (ESCC) progression and its underlying mechanism involving the miR-34a/ZEB1/E-cadherin/EMT pathway. METHODS: XIST and ZEB1 expression were analyzed using quantitative PCR and immunohistochemistry. XIST knockdown was achieved in KYSE150 ESCC cells using siRNA or shRNA lentivirus transfection. Proliferation, migration, and invasion abilities were assessed, and luciferase reporter assays were performed to confirm XIST-miR-34a-ZEB1 interactions. In vivo ESCC growth was evaluated using a xenograft mouse model. RESULTS: XIST and ZEB1 were upregulated in tumor tissues, correlating with metastasis and reduced survival. XIST knockdown inhibited proliferation, migration, and invasion of KYSE150 cells. It decreased ZEB1 expression, increased E-cadherin and miR-34a levels. Luciferase reporter assays confirmed miR-34a binding to XIST and ZEB1. XIST knockdown suppressed xenograft tumor growth. CONCLUSION: XIST promotes ESCC progression via the miR-34a/ZEB1/E-cadherin/EMT pathway. Targeting the XIST/miR-34a/ZEB1 axis holds therapeutic potential and serves as a prognostic biomarker in ESCC.

Real-world data on the first-line immune checkpoint inhibitors or in combination with chemotherapy in older patients (aged ≥ 75 years) with advanced non-small cell lung cancer.

Purpose: The purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. Methods: We enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. Results: In total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. Conclusion: In the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.

Prognostic value of neutrophil to lymphocyte ratio and platelet counts during chemotherapy in patients with advanced gastric cancer.

OBJECTIVES: To investigate the predictive significance of dynamic changes in the neutrophil to lymphocyte ratio (NLR) and platelet counts (PLTs) in patients with advanced gastric cancer (GC) during chemotherapy. METHODS: A total of 259 advanced GC patients receiving chemotherapy were enrolled and grouped by high or low NLR with a cut value of 2.5 and PLT with cut value of 300×109/L. The Kaplan-Meier survival model and the Log-rank test were carried out to determine the comparison on the overall survival differences. Cox regression analysis was employed to carry out both univariate and multivariate regression studies, aiming to explore potential prognostic factors acting independently. RESULTS: Higher pre-chemotherapy NLR exhibited an association with metastasis and advanced grade of Borrmann type, and higher NLR of pre- or post-chemotherapy GC patients was related with Borrmann type grade. Moreover, higher PLT counts are associated with advanced grades of Borrmann type. Interestingly, patients with lower post-chemotherapy NLR or decreasing NLR hold better overall response rate and disease control rate than those with higher NLR or increasing NLR. Furthermore, patients with high post-chemotherapy NLR alone or higher post-chemotherapy NLR plus higher post-chemotherapy PLT. CONCLUSION: Our study suggested that high post-chemotherapy NLR and post-chemotherapy PLT might be adverse prognostic markers in advanced GC patients undergoing chemotherapy.

SCN4B inhibits the progression of lung adenocarcinoma and is associated with better prognosis.

INTRODUCTION: Lung adenocarcinoma (LUAD) is the major type of non-small cell lung cancer with low a survival rate caused by metastasis. SCN4B encoding voltage-gated sodium channel ß subunit is regarded as a metastasis-suppressor gene. We aim to explore how SCN4B influences the progression and prognosis of LUAD. METHODS: The gene expression profiles of 585 LUAD samples in TCGA and GSE31210, GSE116959, and GSE72094 datasets from the GEO database were downloaded for analysis. Differentially expressed genes were obtained through the "limma" package. The "clusterProfiler" package was used to conduct GSEA. Survival analysis was conducted via "survival" and "survminer" packages. Transcription factors regulating SCN4B expression were screened by correlation analysis and further predicted by FIMO. Infiltration of immune cells was analyzed by CIBERSORT. ESTIMATE algorithm was used to evaluate the immune-related scores. RESULTS: SCN4B expressed higher in normal samples than in LUAD samples and higher in female samples than male samples. One hundred and twenty-six pathways were significantly enriched between high and low SCN4B expression groups. Six transcription factors' expressions were positively related to SCN4B expression, and ChIP-seq data from "Cistrome" verified that TAL1 and ERG might bind to the upstream sequence of SCN4B. SCN4B expression was significantly correlated with activated memory CD4 T cells, resting mast cells, and monocytes. TMB status, three scores based on ESTIMATE algorithm, and expression of three immune checkpoints showed significant differences between SCN4B high- and low-expression groups. SCN4B could be considered as an independent prognostic signature of LUAD patients that higher expression represents a better prognosis. CONCLUSION: SCN4B expresses higher in normal samples, and SCN4B is able to be an independent prognostic signature for LUAD patients. TAL1 and ERG may regulate the expression of SCN4B by binding its upstream sequences. Our research is valuable in improving the effectiveness of treatment in LUAD.

Association between baseline C­reactive protein level and survival outcomes for cancer patients treated with immunotherapy: A meta­analysis.

The prognostic impact of baseline C-reactive protein (CRP) in patients with cancer receiving immune checkpoint inhibitors (ICIs) is unclear. The present meta-analysis aimed to review the prognostic value of baseline C-reactive protein (CRP) levels for patients with cancer receiving immunotherapy. Electronic databases, including PubMed, EMbase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, WanFang, Chinese Literature Biomedical Database and Weipu Database, were used to identify cohort studies on the relationship between the baseline CRP levels and ICI survival outcomes from inception to November 2020. Literature screening, data extraction and quality evaluation of studies were independently performed by two reviewers. Subsequently, a meta-analysis was performed using STATA 14.0. A total of 13 cohort studies comprising 2,387 patients with cancer were included in the present meta-analysis. The results indicated that high baseline CRP levels (serum CRP measured within 2 weeks before ICI treatment) were associated with low overall survival (OS) and progression-free survival (PFS) rate among patients treated with ICIs. The subgroup analysis based on cancer type showed that high baseline CRP levels were associated with poor survival outcomes of multiple types of cancer, such as non-small cell lung cancer (6/13; 46.2%), melanoma (2/13; 15.4%), renal cell (3/13; 23.0%) and urothelial carcinoma (2/13; 15.4%). Similar results were observed in subgroup analysis based on the CRP cut-off value of 10 mg/l. In addition, a higher mortality risk was reported in patients with cancer and CRP ≥10 mg/l (hazard ratio, 2.76; 95% CI, 1.70-4.48; P<0.001). Compared with patients with low baseline CRP levels, increased baseline CRP levels were associated with low OS and PFS rate in patients with cancer receiving ICIs. Furthermore, CRP ≥10 mg/l indicated a worse prognosis. Therefore, baseline CRP levels may serve as a marker for the prognosis of patients with certain types of solid tumor treated with ICIs. Due to the limited quality and quantity of included studies, more prospective well-designed studies are required to verify the present findings.

Correlation Analysis between T790M Status and Clinical Characteristics of Patients with EGFR-sensitive Mutation Advanced NSCLC who Progressed after the First-line EGFR-TKIs Administration: A Real-world Exploratory Study.

AIM: The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) administration. METHODS: A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly. RESULTS: The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs 10.9 months, P=0.023) and (median PFS: 14.0 vs 10.1 months, P=0.001). CONCLUSION: This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently.

Multivariate analysis of prognostic factors in patients with lung cancer.

Objective: Lung cancer is the leading cause of cancer-related mortality in China. The purpose of this study was to determine the effect of non-therapeutic and therapeutic factors of patients with lung cancer on survival rate. Methods: In this retrospective study, a total of 458 patients diagnosed as lung cancer at the Department of Thoracic Surgery, the Fourth Affiliated Hospital of Hebei Medical University from September 2008 to October 2013 were enrolled. The COX proportional hazards model was used to analyze the possible factors affecting the survival of patients. Model variables included age, sex, family history, smoking, tumor location, pathological type, stage, chemotherapy, radiotherapy, operation, and targeted therapy. Results: The median survival time (MST) was 32.0 months (95% CI: 29.0-34.0 months), while the 1-, 3-, and 5-year survival rates were 70.74%, 36.90%, and 30.13%, respectively. The univariate analysis showed that stage, chemotherapy, radiotherapy, and operation significantly affected the median survival time of patients. Multivariate cox regression analysis suggested that sex (female vs male, 2.096, 95% CI: 1.606-2.736), stage (stage I vs IV, 0.111, 95% CI: 0.039-0.314; stage II vs IV, 0.218, 95%CI: 0.089-0.535), chemotherapy (no vs yes, 0.469, 95% CI: 0.297-0.742), and operation (no vs yes, 2.667, 95% CI: 1.174-6.055) were independently associated with the survival of patients with lung cancer. Conclusion: Our study showed that male, early stage, operation were protective factors for the survival of patients, while female, advanced stage, chemotherapy were risk factors for the survival of patients. Larger studies are required to address the usefulness of these prognostic factors in defining the management of patients with lung cancer.

Distal-continual colon interposition for esophageal reconstruction after esophagectomy: Two case reports.

Background: Colon interposition is a complex and time-consuming procedure requiring at least three or four digestive anastomoses. However, the long-term functional outcomes are promising, with an acceptable operative risk. Case presentation: Herein, two cases of esophageal carcinoma that received esophagus reconstruction using the distal continual colon interposition technique have been described. The transverse colon was lifted to the thoracic cavity for the end-to-side anastomosis with the esophagus, and a closure device was used to close the colon instead of severing and isolating the distal end. The duration of the operation was 140 and 150 min, respectively. The blood supply of the colon was maintained during the intervention. The tension-free anastomosis was performed without severe complications, and oral food intake was resumed on postoperative day 6. Neither anastomotic stenosis, antiacid or heartburn, dysphagia, or emptying obstacles nor complaints of diarrhea, bloating, or malodor were reported during the follow-up period. Conclusions: The modified distal-continual colon interposition technique may have the advantages of a short operation time and potential prevention of serious complications caused by the torsion of mesocolon vessels.

Comparative clinical analysis of fever in tumor patients, normal patients, and those infected with new coronavirus pneumonia.

BACKGROUND: Under the current epidemic of the coronavirus disease of 2019 (COVID-19), there is a need to distinguish the differences between the laboratory examinations of COVID-19-infected patients, tumor patients with fever, and those with normal fever patients. We aimed to investigate the temperature of tumor patients with different tumor burdens, stages, and cancer types. METHODS: We recruited 3 groups of patients to this study: fever patients with malignant tumors, ordinary fever patients, and confirmed cases of COVID-19, with 31, 55, and 28 cases in each group, respectively. RESULTS: The levels of leukocytes and neutrophils were the highest among non-tumor patients, and the count of COVID-19 was the lowest, with a P value of 0.000. Among the leukocytosis group, non-tumor patients had the highest proportion (43.6%), while that of COVID-19 was only 3.6% (P=0.000). Similarly, there were significant differences in the grading of neutrophils, where most of the infected patients were in the normal group and the P value was 0.000. The lymphocyte count of the tumor group was significantly reduced, with an average of (0.97±0.66) ×109/L (P=0.004). In the lymphocyte grades, most of the infected patients were the normal group (71.4%), while tumor patients in the lymphocytopenia group accounted for 63.1% (P=0.006). There were also significant differences in the neutrophil to lymphocyte ratio (NLR) (P=0.006). There was a significant difference in temperature between different tumor burden groups (P=0.014). CONCLUSIONS: The normal fever group had the highest count of leukocyte and neutrophils, whereas the infected group had the lowest relative count. The NLR was the lowest in the infected group. The NLR was higher in the bigger tumor load group.

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing.

BACKGROUND: This study aimed to use a panel targeting 197 genes and 38 fusions to observe the features of gene variations in lung cancer patients, as well as their prognostic values. METHODS: Patients admitted to our hospital between 2016 and 2017 were enrolled. All patients received OseqTM-Drug genetic testing using peripheral venous blood, followed by 1-2 years of observation. RESULTS: For all included patients, 32 genes were observed with mutations. EGFR exhibited the highest mutation rate (46.5%), followed by TP53. The majority of patients carried only one mutant gene. Interestingly, 18 (41.8%) patients showed no mutations, and some cases carried mutations in six genes simultaneously. There was no statistical relationship between mutations and demographic influence. Pathological subtypes were associated with mutations including FLI1, IGF1R, and NOTCH1. A significant correlation was observed between mutant genes and stage at diagnosis, however this requires further confirmation as there was only one case in these mutations: AKT2, AR, STK11, VEGFA, HDAC6, and ASPSCR. For the 33 patients with lymph node metastases at the time of diagnosis, no correlation with any gene mutant was found. Finally, no associations between the survival or prognosis indices (1-year survival, 1-year progression, progression free survival (PFS), and overall survival (OS)) were observed with gene mutations. CONCLUSIONS: Together, individualized genetic testing is a feasible and minimally invasive approach in cancer genetic analysis. However, gene mutation detection has a limited efficacy in the prediction of prognosis.

Preparation of a Bombyx mori acetylcholinesterase enzyme reagent through chaperone protein disulfide isomerase co-expression strategy in Pichia pastoris for detection of pesticides.

The cholinesterase-based spectrophotometric methods for detection of organophosphate pesticides (OPs) and carbamate pesticides (CPs) have been proposed as a good choice for their high efficiency, simplicity and low cost. The enzyme, as a core reagent, is of great importance for the developed method. In this study, a protein disulfide isomerase (PDI) co-expression strategy in Pichia pastoris was employed to enhance the yield of recombinant Bombyx mori acetylcholinesterase 2 (rBmAChE2). Subsequently, the prepared enzyme reagent was used to detect the pesticides in real samples. The results showed that the co-expression of rBmAChE2 with PDI increased the enzyme activity of the supernatant and the yield of purified rBmAChE2 up to 60 U/mL and 6 mg/L respectively, both almost 5-fold higher than those of original recombinant strain. In addition, 5 g/L gelatin reagent could help to preserve nearly 90% of the rBmAChE2 activity for 90 days in 4°C and the limits of detections (LODs) of the rBmAChE2-based assay for 20 kinds of OPs or CPs ranged from 0.010 to 2.725 mg/kg, which were lower than most of indexes present in current Chinese National Standard (GB/T 5009.199-2003) or the maximum residue limits (GB 2763-2019). Furthermore, the detection results of 23 vegetable samples were verified by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, which indicated that the rBmAChE2-based assay in this work is suitable for pesticide residues rapid detection.

LncRNA PTCSC3 Inhibits Tumor Growth and Cancer Cell Stemness in Gastric Cancer by Interacting with lncRNA Linc-pint.

BACKGROUND: The tumor suppressor role of lncRNA PTCSC3 has been reported in papillary thyroid carcinoma, our study aimed to investigate its involvement in gastric cancer. METHODS: Tumor tissues and adjacent healthy tissues were collected from gastric cancer patients. Expression of PTCSC3 and lncRNA Linc-pint in these tissues was analyzed by RT-qPCR. The interaction between PTCSC3 and Linc-pint was analyzed by overexpression experiments. Cell proliferation and stemness were analyzed by CCK-8 assay and cell stemness assay, respectively. RESULTS: PTCSC3 and lncRNA Linc-pint were both downregulated in tumor tissues than in adjacent healthy tissues of gastric cancer patients. Low levels of PTCSC3 and Linc-pint were closely correlated with poor survival. PTCSC3 and Linc-pint overexpression inhibited tumor growth and cancer cell stemness, while Linc-pint knockdown played an opposite role an attenuated the effects of PTCSC3 overexpression. Expression levels of PTCSC3 and Linc-pint were significantly correlated in tumor tissues but not in adjacent healthy tissues. Overexpression of PTCSC3 and Linc-pint upregulated the expression of each other. CONCLUSION: PTCSC3 inhibits tumor growth and cancer cell stemness in gastric cancer by interacting with lncRNA Linc-pint.

Linc­pint overexpression inhibits the growth of gastric tumors by downregulating HIF­1α.

Long intergenic non­protein coding RNA, p53 induced transcript (Linc­pint) has been reported to be downregulated in various cancer cell lines; however, its expression profile and role in gastric cancer remains unknown. The present study aimed to investigate the involvement of Linc­pint in gastric cancer. Through quantitative polymerase chain reaction, western blotting and viability assays, it was observed that Linc­pint expression was significantly downregulated in gastric biopsies from patients with gastric cancer, compared with healthy controls. Conversely, the expression of hypoxia­inducible factor­1α (HIF­1α) mRNA was significantly upregulated in patients with gastric cancer compared with in healthy controls. Using a variety of statistical inference tests, including receiver operating characteristic curve and correlation analyses, it was determined that the expression levels of Linc­pint and HIF­1α exhibited a significantly negative correlation in patients with gastric cancer but not in healthy controls. Linc­pint expression was significantly and inversely associated with tumor size but not tumor metastasis. Linc­pint overexpression inhibited the proliferation of gastric cancer cells, whereas treatment with exogenous HIF­1α promoted proliferation. Linc­pint overexpression downregulated the expression of HIF­1α, whereas exogenous HIF­1α did not significantly alter Linc­pint expression. Furthermore, treatment with exogenous HIF­1α suppressed the inhibitory effects of Linc­pint overexpression on the proliferation of gastric cancer cells. In conclusion, overexpression of Linc­pint may inhibit the growth of gastric tumors via downregulation of HIF­1α.