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Immunosenescence refers to the immune system undergoing a series of degenerative changes with advancing age and is tightly associated with the initiation and progression of cancers. However, the immunosenescence-related genes as critical biomarkers for bladder cancer (BLCA) have not been systematically analyzed. We retrieved the immunosenescence-related genes from the public database and verified their association with hallmarks of immunosenescence based on The Cancer Genome Atlas (TCGA) cohort. Through gene pairing, Lasso, and univariate Cox regression, an 8-gene pair model was constructed to evaluate the overall survival of BLCA, which was then validated in the training cohort (P < 0.001 , n = 396), two external validation cohorts (P < 0.05 , n = 165 ; P < 0.001 , n = 224), and local samples (P < 0.05 , n = 10). We also downloaded the clinical information and gene expression matrices of other 32 different cancers from TCGA. The established model showed significant predictive value for the prognosis in 15 cancers (P < 0.05). The risk model could also serve as a promising predictor for immunotherapeutic response, which has been verified by the TIDE algorithm (P < 0.05), IMvigor210 dataset (P < 0.01 , n = 298), and other two datasets correlated with immunotherapy (P < 0.05 , n = 56 ; P = 0.17 , n = 27). The TCGA dataset, in vitro cell experiments, and pan-cancer analysis displayed that the gene signature was associated with cisplatin sensitivity (P < 0.05). Overall, we proposed a novel immunosenescence-related gene signature to predict prognosis, immunotherapeutic response, and cisplatin sensitivity of BLCA, which were validated in different independent cohorts, local samples, and pan-cancer analyses. [ABSTRACT FROM AUTHOR]

The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity. [ABSTRACT FROM AUTHOR]

Background. Multiple studies have reported the significance of the systemic immune-inflammation index (SII) in the prognosis of colorectal cancer (CRC), but no consensus has yet been reached. The purpose of this study was to systematically assess the prognostic value of SII in patients with CRC. Materials and Methods. We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for eligible studies. The correlation between pretreatment SII and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in CRC patients was evaluated by combining the hazard ratio (HR) and 95% confidence interval (CI). Results. Twelve studies involving 3919 patients were included. Comprehensive analysis results showed that high SII indicated poor OS in CRC patients (HR = 1.777 , 95% CI: 1.328-2.376). Compared with patients with low SII values, patients with high SII had lower PFS (HR = 1.658 , 95% CI: 1.189-2.311). Subgroup analysis further verified the above results. Conclusions. SII may be a noninvasive and powerful tool for predicting survival outcomes in CRC patients. However, more well-designed studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between programmed death-ligand 1 (PD-L1) coupled with CD8+ tumor-infiltrating lymphocytes (TILS) and the clinicopathological features, along with prognosis of cervical squamous cell carcinoma (CSCC). Methods. 95 patients of CSCC received tumor resection at the Department of Pathology of the First Affiliated Hospital of University of Science and Technology of China (USTC) from 2015 to 2020. Full-automatic immunohistochemistry was applied to measure PD-L1 expression and CD8+ TILS density. Our literature deeply assessed the links between PD-L1 expression, clinicopathological features, and the influences of combination of PD-L1 and CD8+ TILS (PD-L1+/CD8+ TILS) on the prognosis of CSCC. Results. 64.21% of CSCC patients (61/95) expressed PD-L1, and PD-L1 expression was related to the Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, invasion depth, differentiation degree, metastasis of lymph node, and vascular invasion (P < 0.05). Dramatic correlation between PD-L1 expression and CD8+ TILS density was illustrated in CSCC patients (r = − 0.461 , P < 0.001). Obvious differences in differentiation degree, FIGO stage, infiltration depth, and lymph node metastasis were shown between patients with PD-L1 coupled with high-density of CD8+ TILS and those with PD-L1 coupled with low-density of CD8+ TILS (P < 0.05). Patients with PD-L1 negative expression exhibited better prognosis compared with those with PD-L1 positive expression (P < 0.05). Patients with PD-L1 coupled with high-density of CD8+ TILS showed better prognostic status, while those with PD-L1 coupled with low-density of CD8+ TILS had worse prognostic condition (P < 0.05). Differentiation, metastasis of lymph node, and FIGO stage were substantive impact elements of a CSCC patient's overall survival (OS) by Cox multivariate analysis. Conclusions. CD8+ TILS density is related to PD-L1 expression in carcinoma. PD-L1/CD8+ TILS density can be regarded as evaluation for the prognosis of patients with CSCC, providing a new therapeutic target in clinical application. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancy tumors with insidious onset, rapid development and metastasis, and poor prognosis. Therefore, it is necessary to understand molecular mechanisms of HCC and identify clinically useful biomarkers for it. This study aimed to investigate the role of retinoblastoma binding protein 5 (RBBP5) in HCC. The expression level of RBBP5 was examined by immunohistochemistry and western blot. The effect of RBBP5 on cell cycle, proliferation, apoptosis, and drug sensitivity was analyzed. RBBP5 was significantly upregulated in HCC tissues and cells. High RBBP5 expression was significantly associated with elevated level of AFP, advanced TNM stage, high Ki-67 expression, larger tumor size, and poor prognosis. Knockdown of RBBP5 significantly inhibited proliferation of HCC cells through cell cycle arrest. In addition, inhibition of RBBP5 increased the sensitivity of HCC cells to doxorubicin. In conclusion, our findings suggest that RBBP5 plays an important role in the progression of HCC and may serve as a novel biomarker and potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

To investigate the prognostic significance of time to recurrence (TTR) for overall survival (OS) and survival after recurrence (SAR) in patients with localized or regionally advanced cutaneous melanoma. A total of 731 cutaneous melanoma patients with an initial diagnosis of 8th American Joint Committee on Cancer (AJCC) clinical stage I‐III were included in this study. The prognostic factors associated with OS and SAR were estimated through Kaplan‐Meier and Cox regression analysis. Of the total cohort, 329 patients (45%) died, and 418 patients (57%) experienced recurrence. The median follow‐up and TTR were 55.6 months and 9.6 months, respectively. A total of 141 patients (19%) experienced recurrence in <6 months, and 277 patients (38%) experienced recurrence in ≥6 months. Patients with stage III and positive lymph node dissection (LND) were more common in the early TTR group than in the late TTR group. Both the OS and SAR rates at 5 years and 10 years in the early TTR group were significantly poorer than those in the late TTR group (P <.001 and P =.008, respectively). Furthermore, early TTR, along with truncal tumor, higher TNM stage and therapeutic variables (extended resection, LND and adjuvant therapy), were significant independent predictors of worse OS and SAR in multivariate analysis (all P <.05). Early TTR predicts worse survival and could be considered an independent prognostic factor for patients with localized or regionally advanced cutaneous melanoma. TTR should be evaluated in all patients with recurrence to guide post‐recurrence risk stratification and follow‐up schedules. [ABSTRACT FROM AUTHOR]

Background. Several studies have been conducted to investigate the role of cell division cycle-associated 5 (CDCA5) in cancer. Its role in breast cancer, however, remains unknown. Methods. The Gene Expression Omnibus and Cancer Genome Atlas Program databases provided the open-access information needed for the research. The CCK8 and colony formation assays were used to measure cell proliferation. The capacity of breast cancer cells to invade and migrate was assessed using the transwell assay. Results. In our study, CDCA5 was identified as the interested gene through a series of bioinformatics analysis. We found a higher CDCA5 expression level in tissue and cells of breast cancer. Meanwhile, CDCA5 has been linked to increased proliferation, invasion, and migration of breast cancer cells, which was also associated with worse clinical features. The biochemical pathways, in which CDCA5 was engaged, were identified using biological enrichment analysis. Immune infiltration research revealed that CDCA5 was linked to enhanced activity of several immune function terms. Meanwhile, DNA methylation might be responsible for the aberrant level of CDCA5 in tumor tissue. In addition, CDCA5 could significantly increase the paclitaxel and docetaxel sensitivity, indicating that it has the potential for clinical application. Also, we found that CDCA5 is mainly localized in cell nucleoplasm. Moreover, in the breast cancer microenvironment, we found that CDCA5 is mainly expressed in malignant cells, proliferation T cells, and neutrophils. Conclusion. Overall, our findings suggest that CDCA5 is a potential prognostic indicator and target for breast cancer, which can indicate the direction of the relevant research. [ABSTRACT FROM AUTHOR]

Purpose. Gliosarcoma is a histopathological variant of glioblastoma, which is characterized by a biphasic growth pattern consisting of glial and sarcoma components. Owing to its scarcity, data regarding the impact of available treatments on the clinical outcomes of gliosarcoma are inadequate. The purpose of this retrospective cohort study was to analyze the prognostic factors of gliosarcoma. Methods. By screening the clinical database of neurosurgical cases at a single center, patients with gliosarcoma diagnosed histologically from 2013 to 2021 were identified. Clinical, pathological, and molecular data were gathered founded on medical records and follow-up interviews. Prognostic factors were derived using the Cox proportional hazards model with backward stepwise regression analysis. Results. Forty-five GSM patients were included. Median overall survival was 25.6 months (95% CI 8.0–43.1), and median relapse-free survival was 15.2 months (95% CI 9.7–20.8). In multivariable analysis, total resection (p = 0.023 , HR = 0.192 , 95% CI 0.046–0.797) indicated an improved prognosis. And low expression of Ki-67 (p = 0.059 , HR = 2.803 , 95% CI 0.963–8.162) would be likely to show statistical significance. However, there might be no statistically significant survival benefit from radiotherapy with concurrent temozolomide (n = 33 , 73.3%, log-rank p = 0.99) or adjuvant temozolomide (n = 32 , 71.1%, log-rank p = 0.74). Conclusion. This single-center retrospective study with a limited cohort size has demonstrated the treatment of gross total resection and low expression of Ki-67 which are beneficial for patients with GSM, while radiotherapy or temozolomide is not. [ABSTRACT FROM AUTHOR]

Background. Head and neck squamous cell carcinoma (HNSCC) is a frequently lethal malignancy, and the mortality is considerably high. The tumor microenvironment (TME) has been identified as a critical participation in cancer development, treatment, and prognosis. However, competing endogenous RNA (ceRNA) networks grouping with immune/stromal scores of HNSCC patients need to be further illustrated. Therefore, our study aimed to provide clues for searching promising prognostic markers of TME in HNSCC. Materials and Methods. ESTIMATE algorithm was used to calculate immune scores and stromal scores of the enrolled HNSCC patients. Differentially expressed genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified by comparing the expression difference between high and low immune/stromal scores. Then, a ceRNA network and protein-protein interaction (PPI) network were constructed for selecting hub regulators. In addition, survival analysis was performed to access the association between immune scores, stromal scores, and differentially expressed RNAs in the ceRNA network and the overall survival (OS) of HNSCC patients. Then, the GSE65858 datasets from Gene Expression Omnibus (GEO) database was used for verification. At last, the difference between the clinical characteristics and immune cell infiltration in different expression groups of IL10RA, PRF1, and IL2RA was analyzed. Results. Survival analysis showed a better OS in the high immune score group, and then we constructed a ceRNA network composed of 97 DEGs, 79 DELs and 22 DEMs. Within the ceRNA network, FOXP3, IL10RA, STAT5A, PRF1, IL2RA, miR-148a-3p, miR-3065-3p, and lncRNAs, including CXCR2P1, HNRNPA1P21, CTA-384D8.36, and IGHV1OR15-2, were closely correlated with the OS of HNSCC patients. Especially, using the data from GSE65858, we successfully verified that IL10RA, PRF1, and IL2RA were not only significantly upregulated in patients high immune scores, but also their high expressions were associated with longer survival time. In addition, stratified analysis showed that PRF1 and IL2RA might be involved in the mechanism of tumor progress. Conclusion. In conclusion, we constructed a ceRNA network related to the TME of HNSCC, which provides candidates for therapeutic intervention and prognosis evaluation. [ABSTRACT FROM AUTHOR]

Background. Continuous nursing based on 5E rehabilitation mode can improve the physiology and psychology of patients to some extent. The purpose of this study was to explore the effect of continuous nursing of 5E rehabilitation mode on the prevention and prognosis of severe respiratory tract infection in patients with severe tracheotomy in neurosurgery. Objective. To explore the effect of 5E rehabilitation nursing model on the prevention of severe respiratory tract infection and prognosis in patients with severe tracheotomy in neurosurgery. Methods. The starting and ending time of this study is from February 2019 to July 2021. In this paper, 60 patients with severe tracheotomy were divided into the control group and research group according to random number table method. The former group received routine nursing, and the latter group received rehabilitation nursing model based on 5E. The patients' satisfaction, oxygenation index, partial pressure of carbon dioxide, partial pressure of oxygen, SAS, SDS score, incidence of severe respiratory tract infection, and quality of life scores were compared. Results. The nursing satisfaction of the research group was higher than that of the control group (P < 0.05). 24 hours after weaning, the oxygenation index and partial pressure of oxygen in the research group were higher than those in the control group, while the partial pressure of carbon dioxide in the research group was lower than that in the control group (P < 0.05). After nursing, the scores of self-rating anxiety scale and self-rating depression scale in the research group were lower than those in the control group, and the difference was statistically significant (P < 0.05). The incidence of severe respiratory tract infection in the research group was significantly lower than that in the control group (P < 0.05). After nursing, the scores of physiological function, psychological function, social function, and health self-cognition in the research group were lower than those in the control group (P < 0.05). Conclusion. The nursing program of neurosurgical patients with severe tracheotomy based on 5E rehabilitation model can effectively enhance patients' nursing satisfaction, activities of daily living, anxiety, and depression and promote the prognosis. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer (LC) and one of the leading causes of cancer-related death worldwide. LUAD has a low survival rate owing to tumour invasion and metastasis. Circulating tumour cells (CTCs) are precursors of distant metastasis, which are considered to adopt the characteristics of cancer stem cells (CSCs). Therefore, analysing the risk factors of LUAD from the perspective of CTCs may provide novel insights into the metastatic mechanisms and may help to develop diagnostic and therapeutic strategies.Methods: A total of 447 patients from TCGA dataset were included in the training cohort, and 460 patients from the GEO dataset were included in the validation cohort. A CTC-related-gene risk model was constructed using LASSO penalty-Cox analysis, and its predictive value was further verified. Functional enrichment analysis was performed on differentially expressed genes (DEGs), followed by immune correlation analysis based on the results. In addition, western blot, CCK-8 and colony formation assays were used to validate the biological function of RAB26 in LUAD.Results: A novel in-silico CTC-related-gene risk model, named the CTCR model, was constructed, which successfully divided patients into the high- and low-risk groups. The prognosis of the high-risk group was worse than that of the low-risk group. ROC analysis revealed that the risk model outperformed traditional clinical markers in predicting the prognosis of patients with LUAD. Further study demonstrated that the identified DEGs were significantly enriched in immune-related pathways. The immune score of the low-risk group was higher than that of the high-risk group. In addition, RAB26 was found to promote the proliferation of LUAD.Conclusion: A prognostic risk model based on CTC-related genes was successfully constructed, and the relationship between DEGs and tumour immunity was analysed. In addition, RAB26 was found to promote the proliferation of LUAD cells. [ABSTRACT FROM AUTHOR]

Background. Pyroptosis is a form of programmed cell death, playing a significant role in cancer. Glioblastoma multiforme (GBM) is the most common malignant brain tumor. The poor prognosis in GBM due to temozolomide (TMZ) resistance has been widely discussed. Such being the case, the correlation between TMZ resistance and pyroptosis is seldom investigated. On this basis, this paper aims to explore the potential prognostic value of genes related to TMZ resistance and pyroptosis as well as their relationship to the immune microenvironment in GBM. Methods. A total of 103 patients from TCGA were assigned to a training cohort; 190 from CGGA were assigned to a validation cohort. The prognostic risk model reflecting pyroptosis and TMZ resistance was built from the training cohort using multivariate Cox regression and performed validation. RT-qPCR was used to examine the expression of 4 genes from the risk signature. FOXP3 was selected for overexpression and verified using the western blot. The TMZ IC50 of FOXP3-overexpressed cell lines was determined by CCK8. Results. A four genes-based risk signature was established and validated, separating GBM patients into high- and low-risk groups. Compared with the low-risk group, the high-risk group presented worse clinical survival outcomes. Its differential expressed genes were enriched in immune-related pathways and closely related to the immune microenvironment. Moreover, RT-qPCR results suggested that FOXP3, IRF3, and CD274 were significantly upregulated in TMZ-resistant strains, while TP63 was downregulated. FOXP3-overexpressed GBM cell lines had higher TMZ IC50, implying an increased resistance of TMZ. Conclusion. A novel gene signature relevant to pyroptosis and TMZ resistance was constructed and could be used for the prognosis of GBM. The four genes from the risk model might play a potential role in antitumor immunity and serve as therapeutic targets for GBM. [ABSTRACT FROM AUTHOR]

Objective. Due to the molecular heterogeneity of gastric cancer, only minor patients respond to immunotherapeutic schemes. This study is aimed at developing an immune-based gene signature for risk stratification and immunotherapeutic efficacy assessment in gastric cancer. Methods. An immune-based gene signature was developed in gastric cancer by LASSO method in the training set. The predictive performance was validated in the external datasets. KEGG pathways related to risk scores were assessed by GSEA. Based on multivariate Cox regression analysis, a nomogram was established. Sensitivity to chemotherapy drugs was evaluated between high- and low-risk samples. The relationships of risk scores with infiltration levels of immune cells, stromal scores, immune scores, immune cell subgroups, and overall response to anti-PD-L1 therapy were determined. Results. Our results showed that high risk scores were indicative of undesirable survival outcomes both in the training set (p < 0.0001) and the validation set (p = 0.002). Moreover, this signature could independently predict patients' survival (HR: 2.656 (1.919-3.676) and p < 0.001). Subgroup analysis confirmed the sensitivity of this signature in predicting prognosis (all p < 0.05). Cancer-related pathways were primarily enriched in high-risk samples, such as MAPK and TGF-β pathways (p < 0.05). By incorporating stage and the risk score, we established a nomogram for predicting one-, three-, and five-year survival probability. Patients with high-risk scores were more sensitive to chemotherapy drugs (p < 0.05). There was heterogeneity in immune cells between high- and low-risk samples (p < 0.05). Samples with progressive disease exhibited the highest risk score, and those with complete response had the lowest risk score (p < 0.05). Conclusion. This immune-based gene signature might be representative of a promising prognostic classifier for predicting risk stratification and immunotherapeutic efficacy in gastric cancer, assisting personalized therapy and follow-up plan. [ABSTRACT FROM AUTHOR]

Purpose. Hepatocellular carcinoma (HCC), a malignant tumor that exists worldwide, has a high morbidity and mortality rate. Previous studies have reported that lncRNA NR2F1-AS1 plays a critical role in several cancers. Here, we aimed to investigate the biological function of NR2F1-AS1 and its molecular mechanism in the migration and invasion of HCC. Methods. Quantitative real-time PCR (qRT-PCR) was performed to analyze NR2F1-AS1 expression in HCC. The biological function was investigated by transwell invasion and migration assays. The protein level was identified by Western blot. In addition, the downstream targets of NR2F1-AS1 and miR-642a were confirmed by luciferase reporter assays. Results. NR2F1-AS1 was significantly upregulated in HCC and associated with the poor prognosis of HCC patients. Biological function experiments revealed that the silence of NR2F1-AS1 suppressed cell invasion and migration in HCC. More importantly, NR2F1-AS1 directly interacted with miR-642a and negatively regulated miR-642a. DEK was the target of miR-642a, and NR2F1-AS1 positively regulated DEK expression by suppressing miR-642a. Conclusion. Taken together, it is the first time we discovered the interaction of NR2F1-AS1 with miR-642a in modulating HCC cell invasion and migration. [ABSTRACT FROM AUTHOR]

Objectives: This study analyzed a large sample to explain the association of baseline smoking state with long-term prognosis of coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI).Background: Data is limited up to now regarding whether smoker's paradox exists in Chinese population.Methods: A total of 10724 consecutive cases were enrolled from January to December 2013. 2-year clinical outcomes were evaluated among current smokers and nonsmokers. Major adverse coronary event (MACCE) included all-cause death, revascularization, myocardial infarction (MI), and stroke.Results: Current smokers and nonsmokers accounted for 57.1% and 42.9%, respectively. Current smokers were presented with predominant male sex, lower age, and less comorbidities. The rates of 2-year all-cause death were not significantly different among two groups. But the rate of stroke and bleeding was significantly higher in nonsmokers than in current smokers (1.6% and 1.1%, P=0.031; 7.2% and 6.1%, P=0.019). The rate of revascularization was significantly higher in current smokers than in nonsmokers (9.1% and 8.0%, P=0.037). Multivariable Cox regression indicated that, compared with nonsmokers, current smokers were not independently associated with all endpoints (all P>0.05).Conclusions: 2-year all-cause death, MACCE, MI, revascularization, stroke, ST, and bleeding risk were similar between current smokers and nonsmokers in CAD patients undergoing PCI. [ABSTRACT FROM AUTHOR]