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Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 388
Author(s):  
Nobuaki Fujikuni ◽  
Kazuaki Tanabe ◽  
Minoru Hattori ◽  
Yuji Yamamoto ◽  
Hirofumi Tazawa ◽  
...  

Background: The prognostic prolongation effect of reduction surgery for asymptomatic stage IV gastric cancer (GC) is unfavorable; however, its prognostic effect for symptomatic stage IV GC remains unclear. We aimed to compare the prognosis of gastrectomy and gastrojejunostomy for symptomatic stage IV GC. Methods: This multicenter retrospective study analyzed record-based data of patients undergoing palliative surgery for symptomatic stage IV GC in the middle or lower-third regions between January 2015 and December 2019. Patients were divided into distal gastrectomy and gastrojejunostomy groups. We compared clinicopathological features and outcomes after propensity score matching (PSM). Results: Among the 126 patients studied, 46 and 80 underwent distal gastrectomy and gastrojejunostomy, respectively. There was no difference in postoperative complications between the groups. Regarding prognostic factors, surgical procedures and postoperative chemotherapy were significantly different in multivariate analysis. Each group was further subdivided into groups with and without postoperative chemotherapy. After PSM, the data of 21 well-matched patients with postoperative chemotherapy and 8 without postoperative chemotherapy were evaluated. Overall survival was significantly longer in the distal gastrectomy group (p = 0.007 [group with postoperative chemotherapy], p = 0.02 [group without postoperative chemotherapy]). Conclusions: Distal gastrectomy for symptomatic stage IV GC contributes to prognosis with acceptable safety compared to gastrojejunostomy.


2022 ◽  
Vol 11 ◽  
Author(s):  
Jiexia Zhang ◽  
Shuangfeng Tang ◽  
Chunning Zhang ◽  
Mingyao Li ◽  
Yating Zheng ◽  
...  

BackgroundPALB2, a gene in the homologous recombination repair (HRR) pathway of the DNA damage response (DDR), is associated with the efficacy of platinum-based chemotherapy, immunotherapy, and PARP inhibitor therapy in several tumors. However, the PALB2 characteristics, its correlation with immunotherapy biomarker, and the prognostic effect of immunotherapy in non-small cell lung cancer (NSCLC) were unknown.MethodsTumor tissue samples from advanced Chinese NSCLC patients were analyzed by next-generation sequencing (NGS) (panel on 381/733-gene). Tumor mutation burden (TMB) is defined as the total number of somatic non-synonymous mutations in the coding region. Microsatellite instability (MSI) was evaluated by NGS of 500 known MSI loci. Programmed Cell Death-Ligand 1 (PD-L1) expression was evaluated using immunohistochemistry (Dako 22C3 or SP263). One independent cohort (Rizvi2018.NSCLC.240.NGS cohort) containing genomic and clinical data from 240 patients with advanced NSCLC and two cohorts (the OAK and POPLAR study cohort) containing genomic and clinical data from 429 patients with advanced NSCLC were used to analyze the prognostic effect of PALB2 on immunotherapy.ResultsGenetic mutation of 5,227 NSCLC patients were analyzed using NGS, of which 162 (3.1%) harbored germline PALB2 mutation (PALB2gmut) and 87 (1.66%) harbored somatic PALB2 mutation (PALB2smut). In NSCLC patients with PALB2gmut and PALB2smut, the most frequently mutated gene was TP53 (65%, 64%). PALB2smut (14.52 Muts/Mb) was associated with higher TMB (p < 0.001) than PALB wild-type (PALB2wt) (6.15 Muts/Mb). However, there was no significant difference in TMB between PALB2gmut (6.45 Muts/Mb) and PALB2wt (6.15 Muts/Mb) (p = 0.64). There was no difference in PD-L1 expression among PALB2gmut, PALB2smut, and PALB2wt. In the Rizvi2018.NSCLC.240.NGS cohort, there was no difference in progression-free survival (PFS) (HR =1.06, p = 0.93) between PALB2 mutation (3.15 months) and PALB2wt (3.17 months). The OAK and POPLAR study cohort of NSCLC patients showed that there was no difference in overall survival (OS) (HR =1.1, p = 0.75) between PALB2 mutation (10.38 months) and PALB2wt (11.07 months).ConclusionsThese findings suggest that PALB2 may not be used as a biomarker for determining prognosis on immunotherapy in NSCLC.


2022 ◽  
Vol 12 ◽  
Author(s):  
Meihong Gao ◽  
Shuhui Liu ◽  
Yang Qi ◽  
Xinpeng Guo ◽  
Xuequn Shang

Long non-coding RNAs (lncRNAs) play critical roles in cancer through gene expression and immune regulation. Identifying immune-related lncRNA (irlncRNA) characteristics would contribute to dissecting the mechanism of cancer pathogenesis. Some computational methods have been proposed to identify irlncRNA characteristics in human cancers, but most of them are aimed at identifying irlncRNA characteristics in specific cancer. Here, we proposed a new method, ImReLnc, to recognize irlncRNA characteristics for 33 human cancers and predict the pathogenicity levels of these irlncRNAs across cancer types. We first calculated the heuristic correlation coefficient between lncRNAs and mRNAs for immune-related enrichment analysis. Especially, we analyzed the relationship between lncRNAs and 17 immune-related pathways in 33 cancers to recognize the irlncRNA characteristics of each cancer. Then, we calculated the Pscore of the irlncRNA characteristics to evaluate their pathogenicity levels. The results showed that highly pathogenic irlncRNAs appeared in a higher proportion of known disease databases and had a significant prognostic effect on cancer. In addition, it was found that the expression of irlncRNAs in immune cells was higher than that of non-irlncRNAs, and the proportion of irlncRNAs related to the levels of immune infiltration was much higher than that of non-irlncRNAs. Overall, ImReLnc accurately identified the irlncRNA characteristics in multiple cancers based on the heuristic correlation coefficient. More importantly, ImReLnc effectively evaluated the pathogenicity levels of irlncRNAs across cancer types. ImReLnc is freely available at https://github.com/meihonggao/ImReLnc.


2021 ◽  
Author(s):  
Thilo Stolze ◽  
Sabine Franke ◽  
Johannes Haybaeck ◽  
Markus Moehler ◽  
Peter P. Grimminger ◽  
...  

Abstract Purpose. In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings.Methods. Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. Results. MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI: 0.13-3.37, P=0.63) and 1.44 (95% CI: 0.66-3.13, P=0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI: 0.14-0.91, P=0.03), whereas those with MMRp had a HR of 1.18 (95% CI: 0.89-1.58, P=0.26).Conclusion. Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Dechang Zhao ◽  
Rusi Zhang ◽  
Longjun Yang ◽  
Zirui Huang ◽  
Yongbin Lin ◽  
...  

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC.Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1–2, 3–8, and ≥9 lymph nodes) and 3 groups (0, 1–3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis.Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438–0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476–0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups.Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bai-Quan Qiu ◽  
Xia-Hui Lin ◽  
Song-Qing Lai ◽  
Feng Lu ◽  
Kun Lin ◽  
...  

Abstract Background Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. Methods Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. Results We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. Conclusion Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.


2021 ◽  
Author(s):  
Yuying Liu ◽  
Guotian Ruan ◽  
Yizhong Ge ◽  
Qinqin Li ◽  
Qi Zhang ◽  
...  

Abstract Objective: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet–lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC).Methods: A total of 1131 patients with GC (811 men and 320 women, average age: 59.45 years) were evaluated. Receiver operating characteristic curves were used to determine the best cut-off values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. Results: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.06; 95% CI: 0.95-1.18; adjusted P = 0.271). In patients with SII >1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI: 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score, the worse the OS (P<0.001).Conclusion: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A Higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.


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