Correlation of Ktrans derived from dynamic contrast-enhanced MRI with treatment response and survival in locally advanced NSCLC patients undergoing induction immunochemotherapy and concurrent chemoradiotherapy.

PURPOSE: This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments. MATERIAL AND METHODS: Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including Ktrans, Kep, Ve, and Vp were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis. RESULTS: 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The Ktrans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-Ktrans group (n=67, Ktrans＞164.3×10-3/min) and low-Ktrans group (n=44, Ktrans≤164.3×10-3/min) based on the ROC analysis. The high-Ktrans group had a significantly higher objective response rate than the low-Ktrans group (85.1% (57/67) vs 22.7% (10/44), p<0.001). The high-Ktrans group also presented better PFS (median: 21.1 vs 11.3 months, p=0.002) and OS (median: 34.3 vs 15.6 months, p=0.035) than the low-Ktrans group. CONCLUSIONS: Pretreatment Ktrans value emerged as a significant predictor of the early response to induction immunochemotherapy and survival outcomes in unresectable stage III NSCLC patients who underwent immunotherapy-based multimodal treatments. Elevated Ktrans values correlated positively with enhanced treatment response, leading to extended PFS and OS durations.

Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase I Study.

PURPOSE: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT. RESULTS: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively. CONCLUSIONS: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes.

Spleen tyrosine kinase facilitates the progression of papillary thyroid cancer regulated by the hsa_circ_0006417/miR-377-3p axis.

Papillary thyroid cancer (PTC) is a prevalent malignancy worldwide. Spleen tyrosine kinase (SYK) is a crucial enzyme that participates in various biological processes, including cancer progression. This study aims to uncover the biological function of SYK in PTC. SYK expression patterns in PTC were evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and western blot. Cell function assays were performed to assess the effects of SYK on PTC. Bioinformatics analysis was conducted to identify intriguing microRNA (miRNA) and circular RNA (circRNA). Dual-Luciferase Reporter or RNA immunoprecipitation assays were used to investigate the correlation among SYK, miR-377-3p, and hsa_circ_0006417. SYK was upregulated in PTC. Overexpression of SYK exhibited a positive correlation with tumor size, lymph node metastasis, and unfavorable disease-free survival. Functional assays revealed that SYK exerted tumorigenic effect on PTC cells through mTOR/4E-BP1 pathway. Mechanistically, hsa_circ_0006417 and miR-377-3p regulated SYK expression, offering modulating its tumor-promoting effects. Collectively, SYK acts as an oncogene in PTC through mTOR/4E-BP1 pathway, which is regulated by the hsa_circ_0006417/miR-377-3p axis, thereby providing a potential alternative for PTC treatment.

A pilot trial of consolidation bevacizumab after hypo-fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non-squamous non-small-cell lung cancer.

PURPOSE: To determine the feasibility of incorporating bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) for patients with unresectable locally advanced non-squamous non-small-cell lung cancer (LA-NS-NSCLC). PATIENTS AND METHODS: Eligible patients were treated with hypo-RT (40Gy in 10 fractions) followed by hypo-boost (24-28Gy in 6-7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo-CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment-related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), and objective response rate (ORR). All time-to-event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy. RESULTS: Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9-65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0-18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months. CONCLUSIONS: This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration.

CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4.

BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. RESULTS: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. CONCLUSION: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.

Patlak-Ki derived from ultra-high sensitivity dynamic total body [18F]FDG PET/CT correlates with the response to induction immuno-chemotherapy in locally advanced non-small cell lung cancer patients.

PURPOSE: This study aimed to investigate the predictive value of metabolic features in response to induction immuno-chemotherapy in patients with locally advanced non-small cell cancer (LA-NSCLC), using ultra-high sensitivity dynamic total body [18F]FDG PET/CT. METHODS: The study analyzed LA-NSCLC patients who received two cycles of induction immuno-chemotherapy and underwent a 60-min dynamic total body [18F]FDG PET/CT scan before treatment. The primary tumors (PTs) were manually delineated, and their metabolic features, including the Patlak-Ki, Patlak-Intercept, maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were evaluated. The overall response rate (ORR) to induction immuno-chemotherapy was evaluated according to RECIST 1.1 criteria. The Patlak-Ki of PTs was calculated from the 20-60 min frames using the Patlak graphical analysis. The best feature was selected using Laplacian feature importance scores, and an unsupervised K-Means method was applied to cluster patients. ROC curve was used to examine the effect of selected metabolic feature in predicting tumor response to treatment. The targeted next generation sequencing on 1021 genes was conducted. The expressions of CD68, CD86, CD163, CD206, CD33, CD34, Ki67 and VEGFA were assayed through immunohistochemistry. The independent samples t test and the Mann-Whitney U test were applied in the intergroup comparison. Statistical significance was considered at P < 0.05. RESULTS: Thirty-seven LA-NSCLC patients were analyzed between September 2020 and November 2021. All patients received two cycles of induction chemotherapy combined with Nivolumab/ Camrelizumab. The Laplacian scores showed that the Patlak-Ki of PTs had the highest importance for patient clustering, and the unsupervised K-Means derived decision boundary of Patlak-Ki was 2.779 ml/min/100 g. Patients were categorized into two groups based on their Patlak-Ki values: high FDG Patlak-Ki (H-FDG-Ki, Patlak-Ki > 2.779 ml/min/100 g) group (n = 23) and low FDG Patlak-Ki (L-FDG-Ki, Patlak-Ki ≤ 2.779 ml/min/100 g) group (n = 14). The ORR to induction immuno-chemotherapy was 67.6% (25/37) in the whole cohort, with 87% (20/23) in H-FDG-Ki group and 35.7% (5/14) in L-FDG-Ki group (P = 0.001). The sensitivity and specificity of Patlak-Ki in predicting the treatment response were 80% and 75%, respectively [AUC = 0.775 (95%CI 0.605-0.945)]. The expression of CD3+/CD8+ T cells and CD86+/CD163+/CD206+ macrophages were higher in the H-FDG-Ki group, while Ki67, CD33+ myeloid cells, CD34+ micro-vessel density (MVD) and tumor mutation burden (TMB) were comparable between the two groups. CONCLUSIONS: The total body [18F]FDG PET/CT scanner performed a dynamic acquisition of the entire body and clustered LA-NSCLC patients into H-FDG-Ki and L-FDG-Ki groups based on the Patlak-Ki. Patients with H-FDG-Ki demonstrated better response to induction immuno-chemotherapy and higher levels of immune cell infiltration in the PTs compared to those with L-FDG-Ki. Further studies with a larger patient cohort are required to validate these findings.

An exploratory analysis of MR-guided fractionated stereotactic radiotherapy in patients with brain metastases.

Purpose: To assess the feasibility and potential benefits of online adaptive MR-guided fractionated stereotatic radiotherapy (FSRT) in patients with brain metastases (BMs). Methods and materials: Twenty-eight consecutive patients with BMs were treated with FSRT of 30 Gy in 5 fractions on the 1.5 T MR-Linac. The FSRT fractions employed daily MR scans and the contours were utilized to create each adapted plan. The brain lesions and perilesional edema were delineated on MR images of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3, Fx4 and Fx5) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume, Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. Planning target volume (PTV) coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. Results: A total of 28 patients with 88 lesions were evaluated, and 23 patients (23/28, 82.1%) had primary lung adenocarcinoma. Significant tumor volume reduction had been found during FSRT compared to Fx0 for all 88 lesions (median -0.75%, -5.33%, -9.32%, -17.96% and -27.73% at Fx1, Fx2, Fx3, Fx4 and Fx5, p < 0.05). There were 47 (47/88, 53.4%) lesions being accompanied by perilesional edema and the inter-fractional changes were significantly different compared to those without perilesional edema (p < 0.001). Patients with multiple lesions (13/28, 46.4%) had more significant inter-fractional tumor changes than those with single lesion (15/28, 53.6%), including tumor volume reduction and anatomical shift (p < 0.001). PTV coverage of non-adaptive plans was below the prescribed coverage in 26/140 fractions (19%), with 12 (9%) failing by more than 10%. All 140 adaptive fractions met prescribed target coverage. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p < 0.001). Conclusions: Significant inter-fractional tumor changes could be found during FSRT in patients with BMs treated on the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans showed dosimetric benefit in patients with perilesional edema or multiple lesions.

Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

Prognostic value of STC1 in solid tumors: a meta-analysis.

Aim: The prognostic value of STC1 has been evaluated in solid tumors. However, the results remain controversial. Materials & methods: Relevant studies published up to 27 February 2021 were identified by a comprehensive search of the PubMed, EMBASE and Web of Science databases. Hazard ratios (HRs) and odds ratios with 95% CIs were applied to explore the association between STC1 and survival outcome and clinical characteristics. Results: Sixteen articles involving 2942 participants were included in this meta-analysis. The pooled analysis showed that high STC1 expression was significantly associated with worse overall survival (HR: 1.91; 95% CI: 1.63-2.24) and disease-free survival/progression-free survival/relapse-free survival (HR: 2.01; 95% CI: 1.34-3.02). Conclusion: STC1 may be an effective prognostic marker in solid tumors.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of the NT5DC Family in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its incidence is obviously increasing. The NT5DC family has been shown to be involved in the progression of many tumors. However, the biological function of NT5DC family members in HCC is still not well understood. METHODS: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, cBioPortal, GeneMANIA, Metascape, and TIMER were applied to assess the biological function of NT5DC family members in HCC. RESULTS: Most of the NT5DC family members were highly expressed in HCC. High expression of NT5C2, NT5DC2, and NT5DC3 was closely associated with higher tumor stage and poor overall survival (OS). In addition, high NT5DC2 and NT5DC3 expression also predicted poor disease-free survival (DFS). Enrichment analysis revealed that the NT5DC family in HCC mainly involved the IMP metabolic process, purine ribonucleoside monophosphate metabolic process, and purine nucleoside monophosphate metabolic process. The expression of NT5DC family members was closely related to the infiltration of some immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. CONCLUSION: Our findings provided new insights into the biological function and prognostic value of NT5DC family members in HCC.

A Novel Nine-Gene Signature Associated With Immune Infiltration for Predicting Prognosis in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its prognosis remains unsatisfactory. The identification of new and effective markers is helpful for better predicting the prognosis of patients with HCC and for conducting individualized management. The oncogene Aurora kinase A (AURKA) is involved in a variety of tumors; however, its role in liver cancer is poorly understood. The aim of this study was to establish AURKA-related gene signatures for predicting the prognosis of patients with HCC. Methods: We first analyzed the expression of AURKA in liver cancer and its prognostic significance in different data sets. Subsequently, we selected genes with prognostic value related to AURKA and constructed a gene signature based on them. The predictive ability of the gene signature was tested using the HCC cohort development and verification data sets. A nomogram was constructed by integrating the risk score and clinicopathological characteristics. Finally, the influence of the gene signature on the immune microenvironment in HCC was comprehensively analyzed. Results: We found that AURKA was highly expressed in HCC, and it exhibited prognostic value. We selected eight AURKA-related genes with prognostic value through the protein-protein interaction network and successfully constructed a gene signature. The nine-gene signature could effectively stratify the risk of patients with HCC and demonstrated a good ability in predicting survival. The nomogram showed good discrimination and consistency of risk scores. In addition, the high-risk group showed a higher percentage of immune cell infiltration (i.e., macrophages, myeloid dendritic cells, neutrophils, and CD4+T cells). Moreover, the immune checkpoints SIGLEC15, TIGIT, CD274, HAVCR2, and PDCD1LG2 were also higher in the high-risk group versus the low-risk group. Conclusions: This gene signature may be useful prognostic markers and therapeutic targets in patients with HCC.

NTF3 Correlates With Prognosis and Immune Infiltration in Hepatocellular Carcinoma.

Background: The potential role of Neurotrophic factor-3(NTF3) in liver cancer is unknown. Therefore, we aimed to explore the clinical value of NTF3 in hepatocellular carcinoma (HCC). Methods: We used a variety of databases to analyze the expression, relationship with prognosis and immune significance of NTF3 in liver cancer through bioinformatics. Results: NTF3 was low expressed in HCC and was an independent prognostic factor in patients with HCC. CIBERSORT analysis indicated that NTF3 expression was positively correlated with CD4+ cells, mast cells, NK cells, macrophages and B cells in the tumor microenvironment. Furthermore, we found that NTF3 expression was negatively correlated with the immune checkpoints PD-L1, TIGIT and TIM-3. Functional network analysis revealed that NTF3 regulates HCC progression through a variety of cancer-related kinases, transcription factors and signaling pathways. Conclusions: We demonstrate that NTF3 correlates with prognosis and immune infiltration in HCC.

ABL1 Is a Prognostic Marker and Associated with Immune Infiltration in Hepatocellular Carcinoma.

BACKGROUND: The role of ABL1 in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the potential role of ABL1 in the progression of HCC using bioinformatics methods. METHODS: We analyzed the expression, prognostic potential, and immune cell effect of ABL1 in HCC by using a variety of datasets. RESULTS: ABL1 is highly expressed in HCC and associated with unfavorable overall survival (OS) and disease-free survival (DFS). Functional network analysis revealed that ABL1 plays an important role in mitochondrial activity, ATP metabolism, protein translation and metabolism, various neurological diseases, nonalcoholic fatty liver disease, and notch signaling pathway. In addition, we found that ABL1 expression was closely correlated with B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, ABL1 expression was positively associated with the expression levels of immune checkpoint genes, such as PD-1L, TIM3, TIGIT, and CTLA4. CONCLUSION: ABL1 is associated with immune infiltration and prognosis of HCC.

Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers: A meta-analysis.

BACKGROUND: Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers. METHODS: Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses. RESULTS: Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69-2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67-1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86-4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52-0.97). CONCLUSIONS: The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed.

Prognostic significance of microRNA miR-24 in cancers: a meta-analysis.

The prognostic significance of miR-24 in tumors has not been determined. Therefore, we conducted a meta-analysis to systematically assess the correlation between miR-24 and its prognostic value in cancers PubMed, EMBASE, and Web of Science databases were used to search relevant articles (up to 1 October 2020). Studies that evaluated the prognostic value of miR-24 in tumors were included. The hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to evaluate survival outcomes and clinical characteristics. All data analyses were implemented using STATA 12.0 software. A total of 17 studies from 15 articles involving 1705 patients were collected for the meta-analysis. The pooled analysis revealed that elevated miR-24 expression was obviously associated with poor overall survival (OS) (HR = 1.66, 95% CI: 1.20-2.31). Furthermore, we also found that elevated miR-24 expression was positively correlated with tumor size (large or small) and tumor stage (III-IV vs I-II). Elevated miR-24 expression indicates poor prognosis and may be a promising prognostic marker in different cancers. Our findings needed to be verified through further investigations. [Figure: see text].

Prognostic value of miR-142 in solid tumors: a meta-analysis.

Several studies on the prognostic value of microRNA 142 (miR-142) in solid tumors have reported conflicting results. Therefore, the aim of this meta-analysis was to evaluate the relationship between the miR-142 and prognosis in solid tumors. A comprehensive search for relevant studies was conducted until 10 November 2020. Studies that investigated the prognostic significance of the miR-142 in solid tumors were included. The hazard ratio and 95% confidence interval were calculated using a random-effects model. All data analyses were performed using the STATA 12.0 software (Stata Corporation, College Station, TX, U.S.A.). Twenty articles involving 2451 participants were included in the meta-analysis. The results showed that high miR-142 expression was a better predictor of overall survival (OS) (HR = 0.66, 95% CI: 0.47-0.93) and disease-free/progression-free/recurrence-free survival (DFS/PFS/RFS) (HR = 0.71, 95% CI: 0.55-0.91) compared with low miR-142 expression. MiR-142 can be used as an effective prognostic marker for patients with solid tumors. Future large prospective studies are warranted to further confirm the present findings.

Prognostic value of combined pretreatment fibrinogen and neutrophil-lymphocyte ratio in digestive system cancers: a meta-analysis of 17 retrospective studies.

BACKGROUND: Several epidemiological studies have reported the relationship between the combined pretreatment fibrinogen and neutrophil-lymphocyte ratio (F-NLR) and prognosis of digestive system cancers (DSCs). However, the results are controversial. We aimed to assess the prognostic value of F-NLR in patients with DSCs. METHODS: A comprehensive search for relevant studies was conducted until June, 2020. Studies that evaluated the association of the F-NLR score with survival outcome in patients with any DSCs were included. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a fixed-effects model. All data analyses were performed using the STATA 12.0 software. RESULTS: A total of 17 studies involving 5,767 participants were included in the meta-analysis. We found that high F-NLR score was significantly associated with poor overall survival (OS) in patients with DSCs (HR =2.0; 95% CI, 1.78-2.24). In addition, patients with high F-NLR score had poor disease-free survival/progression-free survival/recurrence-free survival (DFS/PFS/RFS) (HR =2.01; 95% CI, 1.47-2.74) and DFS (HR =1.97; 95% CI, 1.35-2.87). Sensitivity analyses for OS confirmed that the results were stable. CONCLUSIONS: High F-NLR score is significantly associated with poor prognostic outcomes in patients with DSCs and can serve as an effective prognostic indicator for the Asian population.

The Prognostic Significance of Combined Pretreatment Fibrinogen and Neutrophil-Lymphocyte Ratio in Various Cancers: A Systematic Review and Meta-Analysis.

PURPOSE: The prognostic value of a new scoring system, termed F-NLR, that combines pretreatment fibrinogen level with neutrophil-lymphocyte ratio has been evaluated in various cancers. However, the results are controversial. The purpose of this study was to comprehensively analyze the prognostic value of F-NLR score in patients with cancers. METHODS: An integrated search of relevant studies was conducted by screening the PubMed and Embase databases. Pooled hazard ratios, with 95% confidence intervals (CIs), for overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were calculated to estimate the prognostic significance of F-NLR score in patients with various tumors. A random effects model was used for comprehensive analysis, and subgroup and meta-regression analyses were used to explore sources of heterogeneity. RESULTS: Thirteen articles reporting data from of 4747 patients were included in the study. Pooled analysis revealed that high F-NLR score was significantly associated with poor OS (HR = 1.77; 95% CI, 1.51-2.08) and poor DFS/PFS (HR = 1.63; 95% CI, 1.30-2.05). Subgroup and meta-regression analyses did not alter the prognostic role of F-NLR score in OS and DFS/PFS. CONCLUSIONS: Increased F-NLR score is significantly associated with poor prognosis in patients with cancers and can serve as an effective prognostic indicator.