Based on cuproptosis-related lncRNAs, a novel prognostic signature for colon adenocarcinoma prognosis, immunotherapy, and chemotherapy response.

Introduction: Colon adenocarcinoma (COAD) is a special pathological subtype of colorectal cancer (CRC) with highly heterogeneous solid tumors with poor prognosis, and novel biomarkers are urgently required to guide its prognosis. Material and methods: RNA-Seq data of COAD were downloaded through The Cancer Genome Atlas (TCGA) database to determine cuproptosis-related lncRNAs (CRLs) using weighted gene co-expression network analysis (WGCNA). The scores of the pathways were calculated by single-sample gene set enrichment analysis (ssGSEA). CRLs that affected prognoses were determined via the univariate COX regression analysis to develop a prognostic model using multivariate COX regression analysis and LASSO regression analysis. The model was assessed by applying Kaplan-Meier (K-M) survival analysis and receiver operating characteristic curves and validated in GSE39582 and GSE17538. The tumor microenvironment (TME), single nucleotide variants (SNV), and immunotherapy response/chemotherapy sensitivity were assessed in high- and low-score subgroups. Finally, the construction of a nomogram was adopted to predict survival rates of COAD patients during years 1, 3, and 5. Results: We found that a high cuproptosis score reduced the survival rates of COAD significantly. A total of five CRLs affecting prognosis were identified, containing AC008494.3, EIF3J-DT, AC016027.1, AL731533.2, and ZEB1-AS1. The ROC curve showed that RiskScore could perform well in predicting the prognosis of COAD. Meanwhile, we found that RiskScore showed good ability in assessing immunotherapy and chemotherapy sensitivity. Finally, the nomogram and decision curves showed that RiskScore would be a powerful predictor for COAD. Conclusion: A novel prognostic model was constructed using CRLs in COAD, and the CRLs in the model were probably a potential therapeutic target. Based on this study, RiskScore was an independent predictor factor, immunotherapy response, and chemotherapy sensitivity for COAD, providing a new scientific basis for COAD prognosis management.

Efficacy and treatment-related adverse events of multi-targeted tyrosine kinase inhibitors in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) are used to treat advanced non-small cell lung cancer (NSCLC). Their efficacy and safety have been studied in randomized controlled trials. AIM: This meta-analysis aimed to summarize the most up-to-date evidence regarding the efficacy and adverse events of TKIs in NSCLC treatment. METHOD: Randomized controlled trials were searched from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The intervention arm was the TKI-containing group, and the control arm was the TKI-free group. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival, and adverse events were extracted and synthesized. The last search was performed in April 2022. Two researchers independently screened articles, extracted data, and evaluated the quality of the included studies. The Cochrane risk-of-bias tool was used to assess the quality of each study. Random or fixed-effect models were used in statistical methods. I2 statistics were used to assess heterogeneity. RESULTS: Thirty-one studies (12,517 patients) were included. Compared to the control group, the TKI group had significantly higher ORR (relative risk RR 1.52, 95% confidence interval, CI [1.29, 1.80], P < 0.05), DCR (RR 1.34, 95%CI [1.19, 1.51], P < 0.05), and prolonged PFS (hazard ratio HR 0.67, 95%CI [0.59, 0.77], P < 0.05). The TKI group showed a higher rate of adverse events (RR 1.70, 95%CI [1.34, 2.16], P < 0.05) and grade 3-5 adverse events (RR 1.59, 95% CI [1.35, 1.88], P < 0.05). CONCLUSION: TKIs could increase ORR and DCR and prolong PFS for advanced NSCLC. Adverse events should be closely monitored.

WITHDRAWN: Diagnostic performance of MASP-2 in the diagnosis of colorectal carcinoma.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The publisher regrets that an error occurred which led to the premature publication of this paper. The publisher apologizes to the authors and the readers for this unfortunate error.

Angiotensin I-converting enzyme gene plays a crucial role in the pathology of carcinomas in colorectal cancer.

Angiotensin I-Converting Enzyme (ACE, CD143) Gene plays a crucial role in the pathology of carcinomas in many cancers including colorectal cancer (CRC). However, the methylation of ACE was rarely reported. In this study, our purpose was to investigate the methylation status of ACE and explored its prognostic value in CRC. The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis while the methylation status of ACE was measured via methylation-specific polymerase chain reaction (MSP). The result demonstrated that ACE expression was up-regulated in tumour tissues and HT-29 cells compared with the controls. ACE was also confirmed to be hypomethylated in CRC. Next, we evaluated the influence of ACE hypomethylation on cell growth. It was proved to be a favourable factor for the cell proliferation, cell colony forming, but an inhibitor for the cell apoptosis of CRC cells according to MST assay, colony forming assay and flow cytometry assay. ACE hypomethylation was also considered to be related to the prognosis of CRC through Cox regression analysis. Taken together, the over-expression of ACE was regulated by its hypomethylation and the ACE hypomethylation might be an independent prognostic indicator in CRC.

Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma.

Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.

Nedaplatin or oxaliplatin combined with paclitaxel and docetaxel as first-line treatment for patients with advanced non-small cell lung cancer.

BACKGROUND: Both nedaplatin and oxaliplatin combined with paclitaxel or docetaxel have demonstrated potent activity in advanced non-small cell lung cancer (NSCLC) patients, but there is no study comparing the difference between these 2 chemotherapy regimens. The aim of this study was to evaluate and compare the efficacy and safety between the combination chemotherapy of nedaplatin or oxaliplatin plus paclitaxel and docetaxel in patients with advanced NSCLC. MATERIAL AND METHODS: We retrospectively reviewed patients with stage III-IV unresectable NSCLC from 1 January 2010 to 31 December 2013 at Southwest Hospital. They all received nedaplatin (80 mg/m2, nedaplatin group) or oxaliplatin (130 mg/m2, oxaliplatin group) combined with paclitaxel (175 mg/m2) or docetaxel (75 mg/m2) as first-line treatment. RESULTS: There are 174 patients enrolled - 123 patients in the nedaplatin group and 51 patients in the oxaliplatin group. The objective response rates were 47.3% and 34.1% and the disease control rates were 87.5% and 79.5% in nedaplatin and oxaliplatin groups, respectively. The progression-free survival time was 10.4 months and 9.6 months (p=0.722) and the overall survival time was 18.5 months and 25.5 months in the nedaplatin and oxaliplatin groups, respectively (p=0.09). Total toxicity was greater in the oxaliplatin group (p=0.008), but there is no significant difference among ¾ grade adverse events between the 2 groups (P=0.595). CONCLUSIONS: The effect of nedaplatin plus paclitaxel and docetaxel is the same as oxaliplatin plus paclitaxel and docetaxel, and the toxicity of nedaplatin is well tolerate as first-line treatment for patients with advanced NSCLC.