CT-based peritumoral radiomics nomogram on prediction of response and survival to induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: The study aims to harness the value of radiomics models combining intratumoral and peritumoral features obtained from pretreatment CT to predict treatment response as well as the survival of LA-NPC(locoregionally advanced nasopharyngeal carcinoma) patients receiving multiple types of induction chemotherapies, including immunotherapy and targeted therapy. METHODS: 276 LA-NPC patients (221 in the training and 55 in the testing cohort) were retrospectively enrolled. Various statistical analyses and feature selection techniques were applied to identify the most relevant radiomics features. Multiple machine learning models were trained and compared to build signatures for the intratumoral and each peritumoral region, along with a clinical signature. The performance of each model was evaluated using different metrics. Subsequently, a nomogram model was constructed by combining the best-performing radiomics and clinical models. RESULTS: In the testing cohort, the nomogram model exhibited an AUC of 0.816, outperforming the other models. The nomogram model's calibration curve showed good agreement between predicted and observed outcomes in both the training and testing sets. When predicting survival, the model's concordance index (C-index) was 0.888 in the training cohort and 0.899 in the testing cohort, indicating its robust predictive ability. CONCLUSION: In conclusion, the combined nomogram model, incorporating radiomics and clinical features, outperformed other models in predicting treatment response and survival outcomes for LA-NPC patients receiving induction chemotherapies. These findings highlight the potential clinical utility of the model, suggesting its value in individualized treatment planning and decision-making.

Cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of patients with metastatic or recurrent nasopharyngeal carcinoma in China.

BACKGROUND: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost-effective in China. The purpose of this study is to evaluate the cost-effectiveness of tislelizumab plus GP for the first-line treatment of R/M NPC from the perspective of the Chinese healthcare system. METHODS: A partitioned survival model with three discrete health states was constructed to evaluate the cost-effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE-309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality-adjusted life years (QALYs), total cost, and incremental cost-benefit ratio (ICER). RESULTS: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost-effective at the willingness-to-pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD-L1 expression had little impact on the ICER of this regimen. CONCLUSION: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first-line treatment, is more cost-effective than the GP regimen in China.

Cost-effectiveness analysis of sintilimab plus IBI305 versus sorafenib for unresectable hepatic cell carcinoma in China.

BACKGROUND: Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first-line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. METHODS: From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost-effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. RESULTS: Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality-adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness-to-pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost-effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. CONCLUSIONS: Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Cost-effectiveness analysis of durvalumab plus chemotherapy as first-line treatment for biliary tract cancer.

Objective: The TOPAZ-1 trial reported a significant survival benefit of durvalumab in combination with chemotherapy for the first-line treatment of biliary tract cancer (BTC). However, no studies have evaluated the economics of this treatment option. The aim of this study was to assess the cost effectiveness of durvalumab plus chemotherapy compared to placebo plus chemotherapy from the perspective of US and Chinese payers. Methods: Based on clinical data from the TOPAZ-1 trial, a Markov model was developed to simulate 10-year life expectancy and total healthcare costs for patients with BTC. The treatment group received durvalumab in combination with chemotherapy and the control group received placebo plus chemotherapy. The primary outcomes analyzed included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainty in the analysis results was assessed by sensitivity analysis. Results: For US payers, the placebo plus chemotherapy group had a total cost of $56,157.05 and a utility of 1.10 QALYs, while the durvalumab plus chemotherapy group had a total cost of $217,069.25, a utility of 1.52 QALYs, resulting in an ICER of $381,864.39/QALY. For Chinese payers, the ICER of durvalumab plus chemotherapy group was $367,608.51/QALY. Sensitivity analysis showed that the analysis was most sensitive to the price of durvalumab. For US and Chinese payers, under the respective willing to pay thresholds, the likelihood of the durvalumab plus chemotherapy arm being cost-effective was 0%. Conclusions: Both in China and in the US, durvalumab in combination with chemotherapy is not a cost-effective option for the first-line treatment of BTC compared with chemotherapy.

m6A-related lncRNA-based immune infiltration characteristic analysis and prognostic model for colonic adenocarcinoma.

BACKGROUND: Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A-associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear. METHODS: We screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model. CONCLUSIONS: Quantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus chemotherapy as the first-line treatment for advanced esophageal cancer.

OBJECTIVE: The KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. METHODS: A Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. RESULTS: The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. CONCLUSIONS: Evidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.

The association between single nucleotide polymorphisms and ovarian cancer risk: A systematic review and network meta-analysis.

BACKGROUND: The relationship between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk remains controversial. This systematic review and network meta-analysis was aimed to determine the association between SNPs and OC risk. METHODS: Several databases (PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang databases, China Science and Technology Journal Database, and China Biology Medicine disc) were searched to summarize the association between SNPs and OC published throughout April 2021. Direct meta-analysis was used to identify SNPs that could predict the incidence of OC. Ranking probability resulting from network meta-analysis and the Thakkinstian's algorithm was used to select the most appropriate gene model. The false positive report probability (FPRP) and Venice criteria were further tested for credible relationships. Subgroup analysis was also carried out to explore whether there are racial differences. RESULTS: A total of 63 genes and 92 SNPs were included in our study after careful consideration. Fok1 rs2228570 is likely a dominant risk factor for the development of OC compared to other selected genes. The dominant gene model of Fok1 rs2228570 (pooled OR = 1.158, 95% CI: 1.068-1.256) was determined to be the most suitable model with a FPRP <0.2 and moderate credibility. CONCLUSIONS: Fok1 rs2228570 is closely linked to OC risk, and the dominant gene model is likely the most appropriate model for estimating OC susceptibility.

Cost-effectiveness analysis of pembrolizumab vs. chemotherapy as second-line treatment for advanced esophageal carcinoma in the United States.

Background: The national Comprehensive Cancer Network has suggested pembrolizumab as a second-line therapy for esophageal squamous cell carcinoma (ESCC) patients with a programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10. However, despite the increased survival rate associated with pembrolizumab in these patient population, the high cost of pembrolizumab may influence its antitumor effect. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared to chemotherapy as second-line treatments for esophageal carcinoma (EC) based on KEYNOTE-181 trial. Methods: A Markov model was constructed using TreeAge 2021 based on three different groups: all intent-to-treat patients (ITT population), patients with ESCC (ESCC population), and patients with a PD-L1 CPS ≥10 (CPS ≥10 population). Incremental cost, Incremental effect, Life-years, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. Analyses were conducted on the setting of a willingness-to-pay threshold of $150,000 from the US perspective. Results: The ICERs for pembrolizumab were $157,589.545 per QALY, $60,238.823 per QALY, and $100,114.929 per QALY compared with chemotherapy in the ITT, ESCC, and CPS≥10 populations, respectively. The ICER of the ITT population was higher than $150,000, suggesting that pembrolizumab was not a cost-effective treatment scheme in patients with a PD-L1 CPS ≤ 10 or esophageal adenocarcinoma. The ICER was < $150,000 in the ESCC and CPS≥10 populations, indicating that pembrolizumab was cost-effective in these two subgroups. Conclusion: The determining of pembrolizumab as a cost-effective second-line therapy for EC in the United States depends on the histologic type and PD-L1 expression.

Cost-Effectiveness Analysis of Sintilimab Combined with Chemotherapy Versus Chemotherapy Alone as the First-Line Treatment for Advanced Esophageal Cancer.

Background: Esophageal cancer has a poor prognosis and currently ranks sixth in global cancer mortality rates. The ORIENT-15 trial showed sintilimab plus chemotherapy significantly improved survival when compared to chemotherapy alone. This study aimed to evaluate the cost-effectiveness of sintilimab, a programmed death-ligand 1 (PD-L1) inhibitor, plus chemotherapy in treating patients with esophageal cancer compared with chemotherapy alone. Methods: A Markov model with a 10-year horizon was developed based on the perspective of the Chinese healthcare payers. We conducted a cost-effectiveness analysis for sintilimab combined with chemotherapy based on a questionnaire. Patients were grouped into the sintilimab group based on a positive score of 10 or more (combined positive score (CPS) ≥ 10 groups), and those with any other PD-L1 expression were randomized into patient groups. We estimated the cost and the effectiveness of sintilimab on the quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) was computed. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness results. Results: In the base-case analysis, compared with chemotherapy alone, the ICER of sintilimab plus chemotherapy for all patients was $21024.05 per QALY, and in the CPS≥10 group, it was $20974.23 per QALY. This was lower than $37653 per QALY. One-way sensitivity analysis demonstrated that ICERs were most sensitive to the price of sintilimab. Conclusion: The study demonstrated that sintilimab plus chemotherapy for advanced esophageal cancer as its first-line treatment would be more cost-effective than chemotherapy alone in Chinese patients.

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma.

Background: The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM. Methods: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results. Results: In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter. Conclusions: The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.

Clinical analysis of 12 patients with primary lymphoepithelial carcinoma of the parotid gland.

BACKGROUND AND PURPOSE: The WHO recently designated salivary gland lymphoepithelial carcinoma as a unique malignant tumor that most commonly occurs in the parotid gland. This is a rare cancer and there are few reports in the literature. Among 854 patients with parotid gland tumors who were admitted to our institution, we diagnosed 12 patients (1.41%) with parotid lymphoepithelial carcinoma. METHODS: Retrospective analysis of 12 patients with parotid lymphoepithelial carcinoma diagnosed by the Department of Pathology, Xiangya Hospital of Central South University. RESULTS: All 12 patients had unilateral parotid gland disease and 8 had cervical lymph node metastasis. Five patients received PCR testing for the Epstein-Barr virus and two were positive. All patients received surgical treatment, two received surgical resection alone, nine received surgery and postoperative radiotherapy and chemotherapy, and one received surgery and postoperative chemotherapy. The postoperative follow-up time ranged from 13 to 77 months. As of the last follow-up, eight patients were tumor-free, one patient was lost to follow-up, and three patients died. The main cause of death was local tumor recurrence and multiple metastases throughout the body. CONCLUSION: Parotid lymphoepithelial carcinoma is a malignant neoplasm characterized by proliferation, invasion, and inclusion of poorly differentiated or undifferentiated carcinoma, and a high rate of metastasis to ipsilateral cervical lymph nodes. The comprehensive treatment method consists of radical resection combined with postoperative radiotherapy and chemotherapy. After this comprehensive treatment, the 1-year, 3-year, and 5-year overall survival rates of our patients were 100%, 78.8%, and 39.4%.

Effect of urinary tract infection on the risk of prosthetic joint infection: A systematic review and meta-analysis.

PURPOSE: Urinary tract infection (UTI) are very common in the general population, however it is unclear whether UTI is a risk factor of prosthetic joint infection (PJI). Our purposes were: (1) To determine whether UTI is a risk factor of PJI after joint replacement, and (2) to determine whether the microorganisms causing PJI and UTI are the same. METHODS: PubMed, Web of Science, the Cochrane Library, and EMBASE were searched systematically for studies. The effect sizes of RR were calculated for included studies that reported raw counts with 95% CIs. The aim 1 of the study is a meta-analysis; the aim 2 is a systematic review. RESULTS: The aim 1 indicated that the risk of PJI was significantly higher in the UTI group than in the control group (RR = 3.17; 95% CI, 2.19-4.59). The aim 2 indicated that the microorganisms of UTI and PJI were the same in the same patient, and these included Enterococcus faecalis, and Pseudomonas, which supports the theory of PJI occurring via the haematogenous route from the genitourinary tract that harbours bacteria in UTI. CONCLUSION: This study identified UTI as being significantly associated with PJI after joint arthroplasty and PJI occurring via the haematogenous route from the genitourinary tract harbouring bacteria in UTI. Therefore, postponing surgery and even treating patients with known UTI preoperatively are recommended.

A systematic review and network meta-analysis of single nucleotide polymorphisms associated with pancreatic cancer risk.

In this meta-analysis, we systematically investigated the correlation between single nucleotide polymorphisms (SNPs) and pancreatic cancer (PC) risk. We searched PubMed, Network Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang databases up to January 2020 for studies on PC risk-associated SNPs. We identified 45 case-control studies (36,360 PC patients and 54,752 non-cancer individuals) relating to investigations of 27 genes and 54 SNPs for this meta-analysis. Direct meta-analysis followed by network meta-analysis and Thakkinstian algorithm analysis showed that homozygous genetic models for CTLA-4 rs231775 (OR =0.326; 95% CI: 0.218-0.488) and VDR rs2228570 (OR = 1.976; 95% CI: 1.496-2.611) and additive gene model for TP53 rs9895829 (OR = 1.231; 95% CI: 1.143-1.326) were significantly associated with PC risk. TP53 rs9895829 was the most optimal SNP for diagnosing PC susceptibility with a false positive report probability < 0.2 at a stringent prior probability value of 0.00001. This systematic review and meta-analysis suggest that TP53 rs9895829, VDR rs2228570, and CTLA-4 rs231775 are significantly associated with PC risk. We also demonstrate that TP53 rs9895829 is a potential diagnostic biomarker for estimating PC risk.

A comprehensive evaluation of single nucleotide polymorphisms associated with atrophic gastritis risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with atrophic gastritis (AG) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with AG. METHODS: To identify all associated studies of SNPs and AG published, databases had been searched through January 2020 from the databases of PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, Embase, the Chinese Science and Technology Periodical Database (VIP), Cochrane Library, and Wanfang databases. With the help of network meta-analysis and Thakkinstian algorithm, the best genetic model with the strongest correlation with AG was selected, the final result - matching to the noteworthy correlation - was obtained by referring to the false positive reporting rate (false positive report probability, FPRP). Based on STREGA's stated criteria, the methodological quality of the data we collected was valued. Both Stata 14.0 and GeMTC will be used for a comprehensive review of the system and will be used in our meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with AG susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with AG susceptibility. REGISTRATION: INPLASY202050016.

A comprehensive evaluation of single nucleotide polymorphisms associated with gastric cancer risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with gastric cancer (GC) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with GC. METHODS: Databases were searched to identify association studies of SNPs and GC published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wan fang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability for noteworthy associations. The methodological quality of data was assessed based on the STrengthening the REporting of Genetic Association Studies statement Stata 14.0 will be used for systematic review and meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with GC susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with GC susceptibility. REGISTRATION: INPLASY202040132.

A comprehensive assessment of single nucleotide polymorphisms associated with pancreatic cancer risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with pancreatic cancer (PC) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with PC. METHODS: Databases were searched to identify association studies of SNPs and PC published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database (VIP) and Wanfang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability (FPRP) for noteworthy associations. The methodological quality of data was assessed based on the STREGA statement Stata 14.0 will be used for systematic review and meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with pancreatic cancer susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with pancreatic cancer susceptibility.Registration: INPLASY202040023.

A comprehensive evaluation of single nucleotide polymorphisms associated with osteosarcoma risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with osteosarcoma (OS) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with OS. METHODS: Databases were searched to identify association studies of SNPs and OS published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wan fang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability for noteworthy associations. The methodological quality of data was assessed based on the STrengthening the REporting of Genetic Association Studies statement Stata 14.0 will be used for systematic review and meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with OS susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with OS susceptibility. REGISTRATION: INPLASY202040023.

A comprehensive evaluation of association between homocysteine levels and single nucleotide polymorphisms with hypertension risk: A protocol of systematic review and network meta-analysis.

BACKGROUND: According to the relevant reports that single nucleotide polymorphisms (SNPs) may contribute to change of homocysteine (HCY) levels and increase the risk of hypertension (HTN). During the inconsistent results, this meta-analysis purpose is systematically review and synthesized relevant data on HCY levels and SNPs in HTN. METHODS: The systematic search database, from the following database to find out the association studies of SNPs and HTN publications up until March 2020 from the databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), the Chinese Science and Technology Periodical Database (VIP) and Wan fang databases, and Chinese Biomedical Literature Database (CBM). Network meta-analysis and Thakkinstian's algorithm were used to select the most appropriate genetic model, along with false positive report probability (FPRP) for noteworthy associations. All statistical analyses were calculated with STATA software (version 14.0; StataCorp, College Station, TX). RESULTS: This meta-analysis will provide high-quality evidence to the effects of SNP on HTN and levels of HCY, and find between SNPs and HTN susceptibility on in all the genetic models, and choose the best one. CONCLUSIONS: This meta-analysis will research which SNP is the most correlated with HTN risk. REGISTRATION: INPLASY202050002.

Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma.

This work aimed to investigate tumor-infiltrating immune cells (TIICs) and immune-associated genes in the tumor microenvironment of osteosarcoma. An algorithm known as ESTIMATE was applied for immune score assessment, and osteosarcoma cases were assigned to the high and low immune score groups. Immune-associated genes between these groups were compared, and an optimal immune-related risk model was built by Cox regression analyses. The deconvolution algorithm (referred to as CIBERSORT) was applied to assess 22 TIICs for their amounts in the osteosarcoma microenvironment. Osteosarcoma cases with high immune score had significantly improved outcome (P<0.01). The proportions of naive B cells and M0 macrophages were significantly lower in high immune score tissues compared with the low immune score group (P<0.05), while the amounts of M1 macrophages, M2 macrophages, and resting dendritic cells were significantly higher (P<0.05). Important immune-associated genes were determined to generate a prognostic model by Cox regression analysis. Interestingly, cases with high risk score had poor outcome (P<0.01). The areas under the curve (AUC) for the risk model in predicting 1, 3 and 5-year survival were 0.634, 0.781, and 0.809, respectively. Gene set enrichment analysis suggested immunosuppression in high-risk osteosarcoma patients, in association with poor outcome.