Poor Prognosis In Terms Research Articles

DNA Methylation and Gene Expression of the Cysteinyl Leukotriene Receptors as a Prognostic and Metastatic Factor for Colorectal Cancer Patients.

Colorectal cancer (CRC), one of the leading causes of cancer-related deaths in the western world, is the third most common cancer for both men and women. As a heterogeneous disease, colon cancer (CC) is caused by both genetic and epigenetic changes. The prognosis for CRC is affected by a variety of features, including late diagnosis, lymph node and distant metastasis. The cysteinyl leukotrienes (CysLT), as leukotriene D4 and C4 (LTD4 and LTC4), are synthesized from arachidonic acid via the 5-lipoxygenase pathway, and play an important role in several types of diseases such as inflammation and cancer. Their effects are mediated via the two main G-protein-coupled receptors, CysLT1R and CysLT2R. Multiple studies from our group observed a significant increase in CysLT1R expression in the poor prognosis group, whereas CysLT2R expression was higher in the good prognosis group of CRC patients. Here, we systematically explored and established the role of the CysLTRs, cysteinyl leukotriene receptor 1(CYSLTR1) and cysteinyl leukotriene receptor 2 (CYSLTR2) gene expression and methylation in the progression and metastasis of CRC using three unique in silico cohorts and one clinical CRC cohort. Primary tumor tissues showed significant CYSLTR1 upregulation compared with matched normal tissues, whereas it was the opposite for the CYSLTR2. Univariate Cox proportional-hazards (CoxPH) analysis yielded a high expression of CYSLTR1 and accurately predicted high-risk patients in terms of overall survival (OS; hazard ratio (HR) = 1.87, p = 0.03) and disease-free survival [DFS] Hazard ratio [HR] = 1.54, p = 0.05). Hypomethylation of the CYSLTR1 gene and hypermethylation of the CYSLTR2 gene were found in CRC patients. The M values of the CpG probes for CYSLTR1 are significantly lower in primary tumor and metastasis samples than in matched normal samples, but those for CYSLTR2 are significantly higher. The differentially upregulated genes between tumor and metastatic samples were uniformly expressed in the high-CYSLTR1 group. Two epithelial-mesenchymal transition (EMT) markers, E-cadherin (CDH1) and vimentin (VIM) were significantly downregulated and upregulated in the high-CYSLTR1 group, respectively, but the result was opposite to that of CYSLTR2 expression in CRC. CDH1 expression was high in patients with less methylated CYSLTR1 but low in those with more methylated CYSLTR2. The EMT-associated observations were also validated in CC SW620 cell-derived colonospheres, which showed decreased E-cadherin expression in the LTD4 stimulated cells, but not in the CysLT1R knockdown SW620 cells. The methylation profiles of the CpG probes for CysLTRs significantly predicted lymph node (area under the curve [AUC] = 0.76, p < 0.0001) and distant (AUC = 0.83, p < 0.0001) metastasis. Intriguingly, the CpG probes cg26848126 (HR = 1.51, p = 0.03) for CYSLTR1, and cg16299590 (HR = 2.14, p = 0.03) for CYSLTR2 significantly predicted poor prognosis in terms of OS, whereas the CpG probe cg16886259 for CYSLTR2 significantly predicts a poor prognosis group in terms of DFS (HR = 2.88, p = 0.03). The CYSLTR1 and CYSLTR2 gene expression and methylation results were successfully validated in a CC patient cohort. In this study, we have demonstrated that CysLTRs' methylation and gene expression profile are associated with the progression, prognosis, and metastasis of CRC, which might be used for the assessment of high-risk CRC patients after validating the result in a larger CRC cohort.

Real-world clinicopathological and molecular characteristics, treatment patterns, and outcomes in patients with KRAS G12C–mutated metastatic colorectal cancer in AACR Project GENIE.

41 Background: KRAS mutation accounts for ~37% of colorectal cancer (CRC), with KRAS G12C occurring in ~3% of CRC tumors. KRAS G12C mutation is associated with poorer prognosis in terms of real-world progression-free survival (rwPFS) and overall survival (OS) compared to other KRAS mutations and KRAS wild-type. As KRAS G12C mutated metastatic CRC (mCRC) is recognized as a discrete potentially druggable target, there is a need to further describe this patient population. This retrospective cohort study provides real-world clinicopathological and molecular characteristics, treatment patterns, and outcomes (OS, rwPFS) in patients with KRAS G12C mutated mCRC. Methods: Adult (≥18 years old) patients diagnosed between 01 January 2009 and 01 February 2019 with KRAS G12C mutated mCRC were assessed from three US academic centers in AACR Project GENIE: Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and Vanderbilt-Ingram Cancer Center. Patient characteristics and treatment patterns were reported, and median OS and rwPFS by line of therapy (LOT) were estimated with the Kaplan-Meier method, including exploratory analyses by co-mutation profile. Results: Among 71 mCRC patients, median age at initial diagnosis was 52.1 years, 59% were women, 83% were White, and 68% had initial stage 4 disease. Co-mutations with an oncogenic, likely oncogenic, or predicted oncogenic OncoKB annotation were assessed, and the most commonly observed were APC in 79% of patients, TP53 in 63%, and PIK3CA in 20%. Only 8% of patients had high tumor mutational burden (&gt;10 mut/Mb), and no patients had microsatellite instability-high among those measured (n=48). Most patients (71%) had evidence of surgical resection in the metastatic setting. Nearly all (93%) patients had received systemic therapy: 15 (23%) had only one LOT, 20 (30%) had only two LOTs, and 31 (47%) had three or more. Most patients received oxaliplatin- or irinotecan-based regimens in the first two LOTs. Median OS from the start of first LOT was 33.5 months (95% CI: 26.9, 37.1), 20.7 months (95% CI: 6.4, 23.2) from start of second LOT, and 15.8 months (95% CI: 3.1, 23.4) from start of third LOT. Median rwPFS from start of first LOT was 20.9 months (95% CI: 8.4, 32.0), 4.0 months (95% CI: 2.2, 9.7) from start of second LOT, and 3.1 months (95% CI: 1.1, 7.2) from start of third LOT. Patients with FBXW7 co-mutation had shorter OS and patients with PIK3CA co-mutation had longer rwPFS, compared to those with KRAS G12C alone. Conclusions: In this select patient cohort with KRAS G12C mutated mCRC from US academic centers, outcomes, particularly rwPFS, were poor in later lines of therapy. Frontline OS and rwPFS were longer than in other similar studies, which may be attributable to the young median age and high proportion of surgical resection in the metastatic setting observed in this cohort.

Roles of IL-7R Induced by Interactions between Cancer Cells and Macrophages in the Progression of Esophageal Squamous Cell Carcinoma.

High infiltration of tumor-associated macrophages (TAMs), which contribute to the progression of several cancer types, is correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). In addition to the previously reported increase in migration and invasion, ESCC cells co-cultured directly with macrophages exhibited enhanced survival and growth. Furthermore, interleukin-related molecules are associated with ESCC; however, the precise mechanism underlying this association is unclear. Therefore, we explored the role of interleukin-related molecules in ESCC progression. A cDNA microarray analysis of monocultured and co-cultured ESCC cells revealed that the interleukin 7 receptor (IL-7R) was upregulated in ESCC cells co-cultured with macrophages. Overexpression of IL-7R promoted the survival and growth of ESCC cells by activating the Akt and Erk1/2 signaling pathways. The IL-7/IL-7R axis also contributed to the promotion of ESCC cell migration via the Akt and Erk1/2 signaling pathways. Furthermore, immunohistochemistry showed that ESCC patients with high IL-7R expression in cancer nests exhibited a trend toward poor prognosis in terms of disease-free survival, and showed significant correlation with increased numbers of infiltrating macrophages and cancer-associated fibroblasts. Therefore, IL-7R, which is upregulated when directly co-cultured with macrophages, may contribute to ESCC progression by promoting the development of various malignant phenotypes in cancer cells.

Assessment of Diagnosis, Prognosis and Immune Infiltration Response to the Expression of the Ferroptosis-Related Molecule HAMP in Clear Cell Renal Cell Carcinoma.

Hepcidin antimicrobial peptide (HAMP) is a key factor in maintaining iron metabolism, which may induce ferroptosis when upregulated. However, its prognostic value and relation to immune infiltrating cells remains unclear. This study analyzed the expression levels of HAMP in the Oncomine, Timer and Ualcan databases, and examined its prognostic potential in KIRC with R programming. The Timer and GEPIA databases were used to estimate the correlations between HAMP and immune infiltration and the markers of immune cells. The intersection genes and the co-expression PPI network were constructed via STRING, R programming and GeneMANIA, and the hub genes were selected with Cytoscape. In addition, we analyzed the gene set enrichment and GO/KEGG pathways by GSEA. Our study revealed higher HAMP expression levels in tumor tissues including KIRC, which were related to poor prognosis in terms of OS, DSS and PFI. The expression of HAMP was positively related to the immune infiltration level of macrophages, Tregs, etc., corresponding with the immune biomarkers. Based on the intersection genes, we constructed the PPI network and used the 10 top hub genes. Further, we performed a pathway enrichment analysis of the gene sets, including Huntington's disease, the JAK-STAT signaling pathway, ammonium ion metabolic process, and so on. In summary, our study gave an insight into the potential prognosis of HAMP, which may act as a diagnostic biomarker and therapeutic target related to immune infiltration in KIRC.

Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.

FLT3−ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3−ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3−ITD mutations. In multivariate analyses, patients with an FLT3−ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3−ITD-mutated patients, median OS gradually decreased according to FLT3−ITD status and ratio (34.3 months FLT3−ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3−ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3−ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3−ITD status in all patients, and we found that the group of FLT3−ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3−ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3−ITD mutations.

Quality of life in glioblastoma after the introduction of temozolomide: a systematic review

Introduction: Gliomas are primary tumors of the central nervous system with an aggressive pattern of progression with a poor prognosis in terms of survival and quality of life. The current standard treatment consists of surgery with maximum excision associated with radiotherapy and chemotherapy, based mostly on the use of temozolomide. Since its introduction, the quality of life of patients undergoing this therapy has not been widely targeted and evaluated. Objective: To verify the quality of life of patients with glioblastoma after the introduction of temozolomide in the therapeutic protocols. Methods: A systematic literature review guided by the PICO and PRISMA protocol was conducted; PubMed, Medline and Lilacs databases were consulted. Results: Initially, 77 studies were found, after selection criteria, 35 articles were analyzed. No statistically significant change was found in overall quality of life in studies that analyzed temozolomide therapy versus different control therapies. Conclusion: The association of temozolomide with surgery and radiotherapy proved to be neutral, with no significant negative or positive impacts on the quality of life of patients with glioblastoma.

Prognostic Value of Preoperative Serological Biomarkers in Patients Undergoing Curative-Intent Cytoreductive Surgery for Colorectal Cancer Peritoneal Metastases

BackgroundCytoreductive surgery (CRS) for peritoneal metastases of colorectal cancer (PMCRC) is associated with a high risk of postoperative morbidity, thus making patient selection of upmost importance. Further to data showing an association between preoperative serological biomarkers and patient outcome in various solid tumors, in this study we aim to evaluate their prognostic value in patients with PMCRC treated with curative intent.Patients and MethodsThis is a retrospective study including patients with PMCRC treated by complete CRS ± HIPEC at our institution between 2011 and 2020. Preoperative serological biomarkers, along with other standard clinicopathological variables, were studied to determine their prognostic value.ResultsA total of 94 out of 108 patients met the inclusion criteria. Forty-three patients (46%) presented with synchronous PM. The median peritoneal cancer index (PCI) was 6. On univariate analysis, a higher neutrophil-to-lymphocyte ratio (NLR) was associated with poor prognosis in terms of overall survival (OS) [cutoff 3.567, hazard ratio (HR) 2.8 (1.4–5.3), p = 0.002], whereas a higher platelet-to-lymphocyte ratio (PLR) predicted favorable prognosis in terms of disease-free survival (DFS) [cutoff 185.4, HR 1.9 (1.07–3.53), p = 0.030]. On multivariate analysis, NLR > 3.567, positive lymph nodes (LNs), and PCI > 7 were independent predictive factors for worse OS, whereas NLR > 3.567 and positive LNs were significantly associated with worse DFS. PLR > 185.4 was associated with better DFS.ConclusionHigh preoperative NLR (> 3.567) and PLR (> 185.4) can predict outcome of patients with PMCRC treated by complete CRS ± HIPEC.

Heterogeneity of contemporary grade group 4 prostate cancer in radical prostatectomy specimens.

The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An exploratory analysis

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome.A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits.A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk.Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs.

Baseline anemia predicts a poor prognosis in patients with non-small cell lung cancer with epidermal growth factor receptor mutations: a retrospective study

BackgroundAnemia is relatively common in cancer patients, and baseline anemia is associated with poor survival in patients with non-small cell lung cancer (NSCLC). However, there is a lack of large-sample studies of patients with NSCLC with epidermal growth factor receptor (EGFR) mutations.MethodsWe retrospectively analyzed anemia‑related data for patients with NSCLC and EGFR mutations who were admitted to Zhejiang Cancer Hospital from January 2013 to June 2019 and treated with targeted therapy. The patients’ clinicopathological features were evaluated by χ2 tests and the relationships between clinical characteristics and prognosis were investigated using Kaplan–Meier and multivariate Cox regression analyses.ResultsA total of 2,029 patients treated with EGFR-tyrosine kinase inhibitors (TKIs) were finally enrolled in this study, of whom 24.6% had baseline anemia. Patients without baseline anemia had longer median overall survival (OS) than patients with baseline anemia (36.10 vs. 29.10 months, P = 0.001), and patients with grade < 2 anemia had longer median OS than those with grade ≥ 2 anemia (35.00 vs. 25.10 months, P < 0.001). Multivariate analyses identified baseline anemia as a factor predicting a poor prognosis in terms of OS in patients with EGFR mutations.ConclusionsBaseline anemia is a significant factor predicting a poor prognosis in terms of OS in patients with NSCLC and EGFR mutations treated with targeted therapy. A higher grade of baseline anemia may also be related to shorter OS. And a higher risk of EGFR-mutated patients who had received targeted therapy could also be observed.

Global longitudinal strain improvement after iron replacement in stable heart failure patients – FER-Strain study

Abstract Background Iron deficiency in patients with heart failure with reduced left ventricular ejection fraction (LVEF) confers a poor prognosis in terms of hospital admissions and mortality, worsening functional class and quality of life. Its replacement with ferric carboxymaltose (FCM) has demonstrated to improve clinical parameters, however, the way it is achieved remains unclear. Improvement of myocardial contractility is proposed as possible hypothesis and global longitudinal strain (GLS) could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of replacement of iron deficiency with FCM on left ventricular global longitudinal strain in patients with stable heart failure with left ventricular ejection fraction &amp;lt;50%. Methods Observational, analytical, longitudinal and prospective study that enrolled 45 patients with stable heart failure with LVEF &amp;lt;50% who presented iron deficiency without anemia defined as serum ferritin &amp;lt;100 μg/L or between 100 and 300 μg/L and the transferrin saturation &amp;lt;20%. Transthoracic echocardiogram, 3D, tissue Doppler imaging and strain were performed, by the same cardiologist, before and four weeks after the iron deficiency replacement with FCM. Results The study population's median age was 71 years, 67% were men, 76% had high blood pressure, 62% dyslipemia and 33% diabetes. At baseline they presented LVEF 32% ±8.75%, LV systolic volume index 62.3ml±29.56ml and LV GLS −9.09%±3.44%. Four weeks after iron deficiency replacement, they had a significant improvement in LVEF (difference 2.51%; 95% confidence interval [CI], 1.74% to 3.29%; P&amp;lt;0.0001), LV systolic volume index (difference −6.68ml; 95% CI −1.91ml to −11.45ml; P=0.007) and LV GLS (difference −1.11%; CI 95%, −0.4% to −1.81%; P=0.003), with a relative benefit in LV GLS of 10.57%. Other echocardiography parameters didn't show significant differences. Conclusion In patients with stable heart failure and LVEF &amp;lt;50%, replacement of iron deficiency with FCM improves systolic parameters, especially left ventricular global longitudinal strain. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Fundaciόn Fisabio (Fomento de la Investigaciόn Sanitaria y Biomédica de la Comunidad Valenciana)

Value of tumor’s depth and width in predicting survival rate in non-muscle- invasive (pT1) bladder cancer

Background: Bladder cancer is classified according to traditional American Joint Committee on Cancer TNM staging. In the absence of nodal (N stage) or distant metastases (M stage), the depth of tumor invasion (T stage) is the most important determination to be made: whether the tumor is invading into or beyond the lamina propria (muscle-invasive bladder cancer) or not (non- muscle-invasive bladder cancer). This study investigated the association between the cutoff value of tumor depth and width and survival rate in non-muscle- invasive (pT1) bladder cancer. Methods: This was a retrospective cohort design of randomly selected, single- centered study. The subjects were patients with pT1 urothelial carcinoma who were diagnosed on transurethral resection of bladder specimens at a tertiary hospital in West Java, Indonesia. The research sample was taken by consecutive sampling from 2015 to 2019. Results: Sixty-four patients from were included in this study. A tumor depth &gt;2 mm resulted in a hazard ratio (HR) of 1.41 (95% confidence interval [CI], 1.27–3.94; p&lt;0.007), with significant difference. A tumor width &gt;2.4 mm also increased HR significantly (3.27; 95% CI, 1.69–5.87; p&lt;0.006). The presence of lymphovascular invasion (LVI) in patients with bladder cancer resulted in an HR of 3.66 (95% CI, 1.5–4.77; p&lt;0.001), with statistically significant difference in overall survival (OS). Conclusion: Tumor invasion depth, tumor width, and LVI appear to be predictive of poor prognosis in terms of OS in patients with pT1 bladder cancer.

Machine learning identification of cuproptosis and necroptosis-associated molecular subtypes to aid in prognosis assessment and immunotherapy response prediction in low-grade glioma.

Both cuproptosis and necroptosis are typical cell death processes that serve essential regulatory roles in the onset and progression of malignancies, including low-grade glioma (LGG). Nonetheless, there remains a paucity of research on cuproptosis and necroptosis-related gene (CNRG) prognostic signature in patients with LGG. We acquired patient data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and captured CNRGs from the well-recognized literature. Firstly, we comprehensively summarized the pan-cancer landscape of CNRGs from the perspective of expression traits, prognostic values, mutation profiles, and pathway regulation. Then, we devised a technique for predicting the clinical efficacy of immunotherapy for LGG patients. Non-negative matrix factorization (NMF) defined by CNRGs with prognostic values was performed to generate molecular subtypes (i.e., C1 and C2). C1 subtype is characterized by poor prognosis in terms of disease-specific survival (DSS), progression-free survival (PFS), and overall survival (OS), more patients with G3 and tumour recurrence, high abundance of immunocyte infiltration, high expression of immune checkpoints, and poor response to immunotherapy. LASSO-SVM-random Forest analysis was performed to aid in developing a novel and robust CNRG-based prognostic signature. LGG patients in the TCGA and GEO databases were categorized into the training and test cohorts, respectively. A five-gene signature, including SQSTM1, ZBP1, PLK1, CFLAR, and FADD, for predicting OS of LGG patients was constructed and its predictive reliability was confirmed in both training and test cohorts. In both the training and the test datasets (cohorts), higher risk scores were linked to a lower OS rate. The time-dependent ROC curve proved that the risk score had outstanding prediction efficiency for LGG patients in the training and test cohorts. Univariate and multivariate Cox regression analyses showed the CNRG-based prognostic signature independently functioned as a risk factor for OS in LGG patients. Furthermore, we developed a highly reliable nomogram to facilitate the clinical practice of the CNRG-based prognostic signature (AUC > 0.9). Collectively, our results gave a promising understanding of cuproptosis and necroptosis in LGG, as well as a tailored prediction tool for prognosis and immunotherapeutic responses in patients.

The non-coding RNA (ncRNA)-mediated high expression of polycomb group factor 1 (PCGF1) is a prognostic biomarker and is correlated with tumor immunity infiltration in liver hepatocellular carcinoma.

BackgroundLiver hepatocellular carcinoma (LIHC) has a poor prognosis worldwide. Polycomb group factor 1 (PCGF1) was recently reported to play a tumor suppressive role in cancers. However, the molecular mechanism and competitive endogenous ribonucleic acid (ceRNA) regulatory networks of PCGF1 in LIHC are still unclear.MethodsWe constructed a PCGF1 ceRNA regulatory network in LIHC and identified potential prognostic markers, especially for tumor immunity. We identified the gene expression profiles and conducted correlation and survival analyses of PCGF1 and the related RNAs. We also explored the clinicopathological features and diagnostic and prognostic values of PCGF1 and constructed a nomogram to predict 1-, 3-, and 5-year survival. Based on a variety of bioinformatics tools, we confirmed the PCGF1-related signaling pathways in LIHC. Finally, the role of PCGF1 in immune cell infiltration was also analyzed.ResultsWe found that PCGF1 was overexpressed in LIHC (P<0.001) and was linked to a poor prognosis in terms of overall survival (OS, P=0.029), the progress-free interval (PFI, P=0.002), and disease-free survival (DFS, P=0.02). Hsa-miR-22-3p was highly negatively correlated with PCGF1. Further, 3 upstream long non-coding RNAs (lncRNAs) (i.e., AC016405.3, BX284668.6, and MIR4435-2HG) were confirmed to further research. PCGF1 was positively associated with pathologic tumor stages (P=0.001), histologic grade (P=0.030), alpha fetoprotein (AFP) level (P=0.030), and vascular invasion (P=0.022). The area under the curve of PCGF1 was 0.983 [confidence interval (CI): 0.972–0.994]. In the multivariate analyses, high PCGF1 expression remained an independent factor associated with OS [hazards ratio (HR): 1.696, P=0.027], DSS (HR: 2.139, P=0.024), and the PFI (HR: 1.512, P=0.034). We found that PCGF1 was involved in some malignancy-associated signaling pathways and plays a role in regulating the immune response.ConclusionsWe confirmed the upstream ceRNA regulatory network of PCGF1 in LIHC. PCGF1 has an oncogenic effect and correlates with tumor immunity.

Prognosis and Treatment for Active and Chronic Antibody-Mediated Rejection in Renal Transplant Recipients; Single Center Experience

The aim of the study was to evaluate the prognostic factors and treatment alternatives of antibody-mediated rejection (ABMR) in renal transplant patients. Three thousand renal transplant patients were included in the study. The patients were first divided into 2 groups. Group 1: ABMR [-] recipients (n=2871), Group 2: ABMR (+) recipients (n=129). ABMR patients were compared among themselves by dividing them into 3 subgroups (early-active, late-active, chronic-active). The study was performed retrospectively. Different combinations of methylprednisolone, intravenous immunoglobulin (IVIG), rituximab, plasmapheresis (PP), anti-thymocyte globulin (ATG) were used in the treatment and the results were compared. Graft survival and functions were worse and the rates of CAD, delayed graft function, BK virus, and cytomegalovirus higher in patients with ABMR. Also, graft survival was lower in patients with serum creatinine ≥3 (P=0.001), GFR <30 (P <0.001), and spot urine protein to creatinine ratio ≥1 (P = 0.042) at the time of diagnosis. High interstitial fibrosis and tubular atrophy scores in chronic ABMR cases and high intimal arteritis scores in active ABMR cases were poor prognostic factors. The study showed that ABMR has a poor prognosis in terms of clinical parameters, and treatment should be individualized according to pathologic findings and graft functions at the time of diagnosis. Pulse methylprednisolone and IVIG should be used in the treatment of all ABMR patients, but PP, rituximab, and ATG should be used in selected cases. ABMR has a poor prognosis and treatment should be individualized.

Bioinformatic analysis of the role of solute carrier-glutamine transporters in breast cancer.

BackgroundBreast cancer (BC) is a highly heterogeneous disease. Solute carriers (SLCs) have been involved in the tumor progression of various cancer types. This study aimed to evaluate the role of these SLC-related glutamine transporters in the prognosis of BC patients by bioinformatics analysis.MethodsThis study examined the transcription and prognostic data for glutamine-related transporters in BC from Oncomine Database, which is currently the largest oncogene microarray database platform in the world. As well as Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier (K-M), and cBioPortal online resources. The Tumor Immune Estimation Resource (TIMER) and GEPIA were also used to examine the relationship between SLCs and immune cell infiltration.ResultsThe expression levels of SLC1A5, SLC3A2, SLC7A5, SLC7A8, and SLC38A1 were higher in BC tissues than normal breast tissues, but the expression level of SLC6A14 was lower. The expression levels of SLC7A5, SLC7A8, SLC6A14, and SLC38A2 were related to a later clinical tumor stage. In the K-M analyses, The K-M curves revealed that patients with high SLC1A5 expression had a poor prognosis (OS HR =1.28, 95% CI: 1.06–1.54; P=0.01). The high expression of SLC3A2 was significantly correlated with a poor prognosis (DMFS HR =1.19, 95% CI: 1.02–1.39; P=0.027). Increased SLC7A5 mRNA levels and decreased SLC7A8 mRNA levels were significantly associated with a poor prognosis in terms of OS, RFS, DMFS and PPS. The high expression of SLC6A14 was significantly correlated with a poor prognosis (PPS HR =1.35, 95% CI: 1.07–1.7; P=0.011). The high expression of SLC38A1 was correlated with a better prognosis than low expression of SLC38A1 (RFS HR =0.84, 95% CI: 0.76–0.93; P=0.00077; DMFS HR =0.78, 95% CI: 0.67–0.91; P=0.0013). The infiltration of immune cells and their marker genes were associated with SLC1A5, SLC3A2, SLC7A5, SLC7A8, SLC6A14, SLC38A1, and SLC38A2 expression. SLC7A5, SLC7A8, SLC38A1, and SLC38A2 have the potential to regulate polarization in tumor-associated macrophages.ConclusionsSLC7A5, SLC7A8, SLC38A1, and SLC38A2 may regulate the polarization of tumor-associated macrophages (TAMs). SLC1A5, SLC3A2, SLC7A5, and SLC6A14 may be promising biomarkers for the BC diagnosis and may represent potential therapeutic targets for these patients.

Associations of radiological features of adipose tissues with postoperative complications and overall survival of gastric cancer patients.

To evaluate the associations of the radiological features of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with the postoperative complications and overall survival (OS) of patients undergoing laparoscopic radical gastrectomy for gastric cancer. One hundred forty-two patients underwent laparoscopic radical gastrectomy for gastric cancer from February 2013 to May 2016. The radiological features of SAT and VAT were studied by preoperative computed tomography, and the relationships between the parameters of adipose tissues and the intraoperative and postoperative conditions and OS rate of patients were evaluated. A positive linear correlation was found between VAT area and operation duration, and a negative linear correlation was found between VAT density and intraoperative blood loss (p < 0.05 in both). VAT area was an independent risk factor for postoperative complications. VAT area and VAT density were independent risk factors for OS in gastric cancer. A high VAT area was an independent risk factor for postoperative complications of gastric cancer, whereas a low VAT area and high VAT density were independent risk factors for poor prognosis in terms of OS in gastric cancer. • A large visceral adipose tissue (VAT) area is an unfavourable factor affecting the outcomes of radical gastrectomy for gastric cancer. • Low VAT density may be more likely to cause intraoperative bleeding. • VAT area and VAT density were independent risk factors for the OS of patients with gastric cancer.

A 10-Year Retrospective Case Series on Wound Dehiscence Following Corneal Transplant.

Background and objectiveCorneal transplants are associated with multiple well-known complications, one of them being wound dehiscence. It results in unfavorable outcomes, such as ocular structure damage, graft failure, repeated surgeries, and possibly a poor prognosis in terms of vision quality. Although the wound site may appear well-healed clinically, as the strength at the graft-host junction is weak, the site is susceptible to dehiscence. Wound dehiscence can be secondary to suture removal and/or trauma. In this study, we assessed the incidence of wound dehiscence secondary to trauma following corneal transplant and evaluated its occurrence in terms of patient age, type of corneal transplant performed, duration between corneal transplantation and wound dehiscence, mechanism of injury, and final outcome.MethodsThis was a case series that included all patients who suffered from wound dehiscence secondary to trauma post-corneal transplant between January 1, 2009, and December 31, 2019, at Hospital Kuala Lumpur.ResultsA total of 492 patients underwent corneal transplant surgery during the 10-year study period. Based on specified inclusion and exclusion criteria, only 13 patients were eligible for inclusion in this study. The incidence of wound dehiscence secondary to trauma post-penetrating keratoplasty (PK) was low (2.64%). Twelve patients had undergone PK, while one patient had undergone deep anterior lamellar keratoplasty (DALK). Blunt ocular trauma post-transplant can cause wound dehiscence regardless of patient age and duration post-corneal transplantation. Males are at a higher risk as their active lifestyle contributes to higher exposure to ocular injury.ConclusionAs corneal transplant patients are at life-long risk of wound dehiscence post-transplant, they must be counseled about this possible risk and the need to take adequate precautions in their daily lives. Based on our findings, the use of newer technologies and partial- rather than full-thickness corneal transplants should be explored further.

Assessment of positive surgical margins in the management of patients after radical prostatectomy for pT2 prostate cancer

Few data are available regarding positive surgical margins (PSM) in patients who underwent surgery for localized prostate cancer (PC). Our objective was to evaluate the impact of PSM on biochemical recurrence-free survival (BRFS) for patients who underwent PC for pT2 tumor without adjuvant treatment. We included each patient who underwent radical prostatectomy for pT2N0 PC between 1988 and 2018. Primary endpoint was biochemical recurrence (BR). BRFS was calculated using Kaplan-Meier method. Univariate and multivariate analyses were used to determine factors associated with BR and PSM. Overall, 2429 patients were included whom 420 patients had PSM (17.3%). Median follow-up was 116 months. BRFS at 10 years was 66.6% in case of PSM, and 84% in the negative margins group (P<0.0001). Parameters associated with BR were preoperative PSA level (P<0.0001), Gleason score (P<0.0001), tumor volume in biopsies, and margins length (P<0.04). PSM in pT2N0 CP are associated with poor prognosis in terms of BR. Nevertheless, only a small number of pT2R1 cancer will present biological recurrence. The use of adjuvant radiotherapy in these patients therefore represents a risk of overtreatment, with the risk of adverse effects inherent to irradiation. Clinical and biological monitoring in case of PSM seems acceptable.

Interstitial lung disease in Primary Sj\xf6gren's syndrome

BackgroundInterstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren’s syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms.MethodsData of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics.ResultsSixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud’s phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease.ConclusionsInterstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud’s phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms.