Case report: A case of rare metastasis of gastric cancer to the axillary lymph node metastasis treated with combination immunotherapy.

Lymph node (LN) metastasis is a common mode of metastasis in advanced gastric cancer (GC), while axillary LN metastasis infrequently occurs in GC. There are few reports on this rare type of metastasis - especially its clinicopathological features - and systemic treatment are unclear. We describe a case of GC with extensive metastasis, including the rare axillary LN metastasis. The patient achieved partial response of optimal efficacy, who was treated with combination immunotherapy as second-line treatment for nearly two years. The potential mechanisms were revealed by clinical and immune characteristics, such as high expression of PD-L1, high tumor mutational burden (TMB-H), Epstein-Barr virus (EBV) positive and CD8+ tumor-infiltrating lymphocyte positive.

Using stacked deep learning models based on PET/CT images and clinical data to predict EGFR mutations in lung cancer.

Purpose: To determine whether stacked deep learning models based on PET/CT images and clinical data can help to predict epidermal growth factor receptor (EGFR) mutations in lung cancer. Methods: We analyzed data from two public datasets of patients who underwent 18F-FDG PET/CT. Three PET deep learning ResNet models and one CT deep learning ResNet model were trained as low-level predictors based on PET and CT images, respectively. A high-level Support Vector Machine model (Stack PET/CT and Clinical model) was trained using the prediction results of the low-level predictors and clinical data. The clinical data included sex, age, smoking history, SUVmax and SUVmean of the lesion. Fivefold cross-validation was used in this study to validate the prediction performance of the models. The predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves. The area under the curve (AUC) was calculated. Results: One hundred forty-seven patients were included in this study. Among them, 37/147 cases were EGFR mutations, and 110/147 cases were EGFR wild-type. The ROC analysis showed that the Stack PET/CT & Clinical model had the best performance (AUC = 0.85 ± 0.09), with 0.76, 0.85 and 0.83 in sensitivity, specificity and accuracy, respectively. Three ResNet PET models had relatively higher AUCs (0.82 ± 0.07, 0.80 ± 0.08 and 0.79 ± 0.07) and outperformed the CT model (AUC = 0.58 ± 0.12). Conclusion: Using stack generalization, the deep learning model was able to efficiently combine the anatomic and biological imaging information gathered from PET/CT images with clinical data. This stacked deep learning model showed a strong ability to predict EGFR mutations with high accuracy.

Prognostic significance of PTOV1 expression in cancers: A protocol for systematic review and meta-analysis.

BACKGROUND: Prostate tumor overexpressed-1 (PTOV1) was firstly depicted as gene and protein overexpressed in prostate cancers and preneoplastic lesions of high-grad intraepithelial neoplasia. Recently, people have paid recent attention to the oncogenic PTOV1 protein as a regulator with various cellular functions and pathways that tend to enhance cell growth and self-renewal in numerous cancer cell types. Its prognostic role in cancers remains controversial. METHODS: Eligible studies are identified by comprehensively searching literature in all available databases. The associations between PTOV1 expression and overall survival, disease-free survival, relapse-free survival, progression-free survival, and clinicopathological characteristics are estimated by employing hazard ratios and the confidence intervals of 95%. STATA 12.0 software was adopted to perform the meta-analysis. RESULTS: This study will provide high-quality synthesis to evaluate the associations between PTOV1 expression and overall survival, disease-free survival /relapse-free survival , progression-free survival, and clinicopathological features. CONCLUSION: The study will provide updated evidence to assess whether the expression of PTOV1 is in association with poor prognosis in patients with cancers. PROSPERO REGISTRATION NUMBER: CRD42020183853.

Myosteatosis reduces overall survival in patients with digestive system malignancies: a meta-analysis with trial sequential analysis.

The impact of myosteatosis on the outcomes of digestive malignancies has gained great attention recently. However, studies on the impact of myosteatosis show inconsistent results. We conducted a meta-analysis to clarify the relationship between myosteatosis and the overall survival of digestive cancer patients. The systematic literature search was conducted on PubMed/MEDLINE, Web of Science, and Embase from inception through March 27, 2021. Meta-analysis was performed using the random-effects model. Out of 3451 studies screened, 47 studies including 21,194 patients passed the screening criteria. The average prevalence of myosteatosis was 46.4%. Patients with myosteatosis had 44% increased mortality risk compared with non-myosteatosis patients (HR: 1.44, 95% CI: 1.33-1.55, P < .05). The predictive value of myosteatosis held regardless of country zone, study design, statistical model, Newcastle-Ottawa Scale (NOS) scores, treatment, sample size, and tumor stage. Nevertheless, the predictive value of myosteatosis was only evident for patients with esophagogastric cancers, cholangiocarcinoma/pancreatic cancers, or colorectal cancers. Overall, the results of this meta-analysis were robust based on sensitivity, subgroup, meta-regression, and trial sequential analyses and suggested that myosteatosis predicted worse overall survival (OS) in digestive malignancies patients.

Pretreatment albumin-to-alkaline phosphatase ratio as a prognostic indicator in solid cancers: A meta-analysis with trial sequential analysis.

BACKGROUND: Albumin-to-alkaline phosphatase ratio (AAPR), a novel and economic serum biomarker, is associated with survival in patients with cancer. This study aimed to evaluate the potential role of AAPR as a prognostic indicator of solid cancers. METHODS: This meta-analysis with trial sequential analysis of retrospective studies was designed to investigate the relationship between AAPR and overall survival (OS) in solid cancers. The meta-analysis included 5951 patients from 20 cohorts. The main predictor variable was AAPR, and the main outcome was OS. Statistical tests were performed using Stata 12.0, Revman 5.3, and R 3.6.1. RESULTS: Compared to patients with a lower AAPR, those with a higher AAPR had a better OS (hazard ratio [HR]: 0.50; 95% confidence interval [CI]: 0.43-0.58; p < 0.001). Subgroup analysis by tumor type indicated that a higher AAPR was associated with a better OS in non-small cell lung cancer (HR: 0.45; 95% CI: 0.26-0.78; p < 0.001), small cell lung cancer (HR: 0.60; 95% CI: 0.44-0.82; p < 0.001), hepatocellular carcinoma (HR: 0.49; 95% CI: 0.34-0.69; p < 0.001), pancreatic ductal adenocarcinoma (HR: 0.47; 95% CI: 0.31-0.71; p < 0.001), and nasopharyngeal carcinoma (HR: 0.42; 95% CI: 0.21-0.85; p = 0.016). CONCLUSION: Pretreatment AAPR may be a useful prognostic indicator in solid cancers.

Prognostic Value of Circular RNA ciRS-7 in Various Cancers: A PRISMA-Compliant Meta-Analysis.

BACKGROUND: Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis. As a member of circRNAs, ciRS-7 is thought to be a negative prognostic indicator in multiple types of cancer. The present study aimed to comprehensively explore the value of ciRS-7 in tumor malignancy. Materials and Methods. A systematic review of PubMed, Web of Science, and the Cochrane library was carried out to examine the related studies. The pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from the available publications by STATA 12.0. Subgroup analysis, publication bias, sensitivity analysis, and meta-regression were conducted. RESULTS: This meta-analysis included 1,714 patients from 13 cohorts. The results suggested that high ciRS-7 expression was significantly associated with overall survival (OS) (HR = 2.17, 95% CI = 1.50-3.15, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07. CONCLUSIONS: High expression of ciRS-7 has a significant correlation with the high stage in various cancers, and ciRS-7 is intimately associated with an adverse OS in numerous cancers. Thus, ciRS-7 may act as a potential biomarker for the development of malignancies.

Glycolysis-Based Genes Associated with the Clinical Outcome of Pancreatic Ductal Adenocarcinoma Identified by The Cancer Genome Atlas Data Analysis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadly tumors in digestive tract tumors. Although there has been advancement in PDAC treatment, its prognosis still remains unsatisfactory, mainly because of dismal diagnosis. This article aims to develop new prognostic factors related to energy metabolism in PDAC and to use these genes for novel risk stratification. Hundred fifty messenger RNA (mRNA) expression profiles and clinicopathological data of PDAC were downloaded from The Cancer Genome Atlas dataset. The glycolysis pathway was the significant pathway based on the gene set enrichment analysis. We chose the glycolysis pathway-related 176 genes for further analysis. Multivariate Cox regression analysis and forward stepwise Cox regression model established a novel three-gene glycolytic signature (including MET, B3GNT3, and SPAG4) for PDAC patients' prognosis prediction. All 150 patients were classified into two groups by the median risk score. High-risk group had a worse outcome compared to the low-risk group. The risk score was also significantly correlated with age and radiotherapy. A nomogram, including the glycolytic gene signature, has shown some clinical net benefit for overall survival prediction. We also validated the validity and reliability in the Puleo dataset. This novel gene expression signature may be involved in the pathophysiology and used for risk stratification and prognosis prediction in PDAC.

SNF2 histone linker PHD RING helicase related Has_circ_0001649 as a diagnostic and prognostic biomarker in solid cancer: A PRISMA-compliant meta-analysis based on the Chinese population.

BACKGROUND: Dysregulated circular RNAs have been implicated in the pathogenesis of cancer. Recent studies indicate that has_circ_0001649 lowly expressed in multiple types of cancer. The purpose of this study is to investigate the roles of has_circ_0001649 as a diagnostic and prognostic marker for Chinese patients with cancer. METHODS: Adhering to preferred reporting items for systematic reviews and meta-analyses guidelines, systematic literature searches were performed using Pubmed, Embase, and the web of Science to retrieve articles fulfilled all inclusion criteria. The significance of has_circ_0001649 in diagnosis and prognosis of cancer patients were evaluated. Meta-Disc 1. 4 and STATA 12. 0 were used to analyze the data from collected studies. RESULTS: Eleven articles with 761 patients were included in present meta-analysis, of which 4 were about diagnosis, 5 were about prognosis, and 6 were about tumor differentiation grade. For the diagnostic value of has_circ_0001649, the pooled results for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with their 95% confidential intervals were 0. 78 (0. 73-0. 83), 0. 75 (0. 70-0. 80), 3. 17 (2. 56-3. 93), 0. 29 (0. 23-0. 36), and 11. 41 (7. 80-16. 7), respectively. The area under the curve of summary receiver operator characteristic was 0.8408 (Q = 0. 7725). Meanwhile, the result showed no obvious publication bias in this analysis for the P-value of Deeks' test was .489. For the prognostic value, the pooled hazard ratio for overall survival was 0.45 (0.324-0.626). Lower expression of has_circ_0001649 was also prone to lower tumor differentiation grade (odds ratio = 2.58, P < .0001). CONCLUSIONS: Has_circ_0001649 could be used as a potential biomarker for diagnosis and prognosis in solid cancer. Further prospective studies are required to validate its clinical application.

hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer.

PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. MATERIALS AND METHODS: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. RESULTS: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). CONCLUSION: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT.

Prognostic Role of the Prognostic Nutritional Index in Pancreatic Cancer: A Meta-analysis.

OBJECTIVE: The prognostic nutritional index (PNI) has been reported to play an important prognostic role in various malignancies. Here we performed a meta-analysis to explore the predictive value of PNI in pancreatic cancer (PC). METHODS: Clinical studies about PNI and prognosis in PC were retrieved from Pubmed, Embase, Web of Science and Cochrane Libarary updated on 31 December 2017. Stata 12 was used to compute pooled hazard radio (HR) and 95% confidence interval (CI) to estimate the relationship between PNI and overall survival (OS). RESULTS: Ten studies with 2064 patients were eligible for final analysis. The pooled HR (1.48, 95%CI: 1.32-1.66, I 2 = 25.5% P = 0.201）revealed that low PNI was related to poor prognosis in patients with PC. The significant relationship between PNI and prognosis was not affected by subgroup analysis based on tumor stage, treatment method, sample size, cutoff value, HR data source and study quality. CONCLUSION: Our meta-analysis suggests PNI maybe a potential prognostic indicator for patients with PC.

MAGI1 Inhibits the Proliferation, Migration and Invasion of Glioma Cells.

BACKGROUND: Membrane-associated guanylate kinase inverted repeat member 1 (MAGI1) acts as a tumor suppressor in a variety of tumors; however, its expression and biological function in glioma are still unknown. METHODS: MAGI1 expression in glioma was examined by immunohistochemistry. In addition, overexpression of MAGI1 in U87 and U373 cells, colony formation and MTT assays were used to evaluate cell proliferation, Transwell assays to determine cell migration and invasion, and a xenograft model established using U87 cells to evaluate the effect of MAGI1 overexpression in vivo. Western blot assays were used to analyze the Akt, MMP2, MMP9 and E-cadherin/N-cadherin/vimentin pathway changes after overexpression of MAGI1. RESULTS: We demonstrated that MAGI1 was expressed at low levels in glioma. Low MAGI1 expression was positively correlated with the malignant progression of glioma and indicated a poor prognosis. Moreover, we found that overexpressed MAGI1 inhibited the proliferation, migration and invasion of glioma cells by regulating cell growth and EMT through Akt, MMP2, MMP9 and the E-cadherin/N-cadherin/vimentin pathway. CONCLUSION: These findings demonstrate a novel function of MAGI1 in glioma progression and suggest that MAGI1 might be a target for the diagnosis and treatment of glioma.

Prognostic and clinicopathological significance of CCAT2 in Chinese patients with various tumors.

BACKGROUND: Colon cancer-associated transcript 2 (CCAT2) as a long noncoding RNA (lncRNA) is overexpressed and plays a significant prognostic role in patients with tumors. The present study aimed to comprehensively evaluate the clinical value of CCAT2 in the Chinese population, as a potential prognostic marker in multiple cancers. METHODS: A systematic search of eligible studies was conducted in the PubMed, Web of Science, Cochrane Library, Wanfang and the China National Knowledge Infrastructure databases as of March 31, 2017. Approximately 1,711 tumor patients from 16 eligible studies were selected. Analyses of the pooled data were performed, and the odds ratio (OR) or hazard ratio (HR) and the 95% confidence interval (95% CI) were calculated and summarized to evaluate the strength of this association using a fixed- or random-effects model. RESULTS: Overall analyses showed that increased CCAT2 expression was associated with a higher risk of lymph node metastasis (LNM), an increased potential for distant metastasis (DM) and higher clinical stage (p<0.001 for LNM, p = 0.001 for DM, p<0.001 for clinical stage). HR and the 95% CI for overall survival (OS) were assessed to pool the effect size using a fixed-effects model. A significant association was observed between increased CCAT2 expression and poor OS (pooled HR = 1.91, 95% CI, 1.63-2.22, p<0.001). CONCLUSIONS: These results indicate that CCAT2 is a biomarker to predict tumor progression and a potential prognostic marker in multiple cancers. Additional well-designed clinical studies are needed to validate these findings.

Prognostic Role of the Pretreatment C-Reactive Protein/Albumin Ratio in Solid Cancers: A Meta-Analysis.

The C-reactive protein/albumin ratio (CAR) has been shown to play a significant prognostic role in several cancers. We aimed to comprehensively explore the potential role of the CAR as a prognostic indicator in solid cancers. In this meta-analysis, we collected data from 10 studies that examined the association between serum CAR and overall survival in patients with cancer. This meta-analysis included 4592 tumor patients. The eligible studies were found through the PubMed and Web of Science databases updated on 6 Oct 2016. The pooled hazard ratio (2.01, 95% CI: 1.58-2.56, p < 0.001) indicated that high CAR yielded worse survival in different cancers. Subgroup analyses showed a significant association between CAR and prognosis, regardless of the cutoff value, cutoff value selection, treatment method, country, sample size, stage and cancer type. This meta-analysis suggests that CAR may be a potential prognostic marker in solid cancers. However, further large prospective studies should be conducted to explore the critical role of CAR in survival of cancer patients.

[Dosimetric comparing between protons beam and photons beam
for lung cancer radiotherapy: a meta-analysis].

BACKGROUND AND OBJECTIVE: The clinical evidences are not sufficient on the proton beam therapy of lung cancer for lacking of the RCTs on the comparing the proton with the photon beam in lung cancer radiotherapy. The aim of this study is to evaluate the dosimetry superiority of the proton beam and provide more valuable evidences to the clinical researches. METHODS: Clinical trails of dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy were obtained from the Cochrane library, Pubmed, EMbase, CBM, CNKI, VIP, and Wan Fang databases. The data included in the study were evaluated and analyzed using the Cochrane Collaboration's RevMan 5.2 software. RESULTS: Six trails were included. Compared to photon therapy (three-dimensional conformal photon radiotherapy, 3D-CRT), the proton therapy had a significantly lower total lung Dmean (MD=-4.15, 95%CI: -5.56--2.74, P<0.001) and V20, V10, V5 (MD=-10.92, 95%CI: -13.23--8.62, P<0.001); The V20, V10, V5 significantly decreased in proton therapy group. Compared to photon therapy (intensity-modulated photon radiotherapy, IMRT), V20, V10, V5 were also significantly lowered in proton therapy group (MD=-3.70, 95%CI: -5.31--2.10, P<0.001; MD=-8.86, 95%CI: -10.74--6.98, P<0.001; MD=-20.13, 95%CI: -27.11--13.14, P<0.001); The esophagus Dmean was not lowered, while the heart Dmean decreased in proton therapy group. CONCLUSIONS: Comparing to photon beam radiotherapy (3D-CRT and IMRT), proton beam therapy is advantageous in dosimetry of the lung cancer radiotherapy and recommended for clinical applying.