Prognostic Marker In Patients Research Articles

BMP Signaling Is a Prognostic Marker in Patients With Colorectal Cancer and Associates With Frailty.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily of ligands and have been shown to promote or suppress colorectal cancer (CRC) growth. Developing treatments that target BMPs is challenging due to their multiple roles, including involvement in the inflammatory response and nutritional status. The present study evaluated the prognostic value of BMP-4, which is believed to be highly expressed in CRC, and its correlation with inflammatory and nutrition statuses in patients with CRC. We analyzed BMP-4 expression in tumor tissues from 144 patients who underwent CRC surgery using immunohistochemistry and evaluated the relationship between BMP-4 levels and clinical outcomes. Kaplan-Meier analysis revealed that patients with high expression levels of BMP-4 exhibited a shorter overall survival rate than those with low levels of expression. Multivariate analysis revealed that BMP-4 expression was an independent prognostic factor for overall survival and death from other diseases in CRC patients. Furthermore, high BMP-4 expression was significantly correlated with high C-reactive protein/Albumin ratio, sarcopenia, and osteopenia. BMP-4 is a significant prognostic factor in CRC, particularly in predicting death from other diseases, while also showing associations with inflammatory and nutritional statuses.

PRDM1 rs2185379, unlike BRCA1, is not a prognostic marker in patients with advanced ovarian cancer.

Ovarian cancer (OC) is mostly diagnosed in advanced stages with high incidence-to-mortality rate. Nevertheless, some patients achieve long-term disease-free survival. However, the prognostic markers have not been well established. The primary objective of this study was to analyse the association of the suggested prognostic marker rs2185379 in PRDM1 with long-term survival in a large independent cohort of advanced OC patients. We genotyped 545 well-characterized advanced OC patients. All patients were tested for OC predisposition. The effect of PRDM1 rs2185379 and other monitored clinicopathological and genetic variables on survival were analysed. The univariate analysis revealed no significant effect of PRDM1 rs2185379 on survival whereas significantly worse prognosis was observed in postmenopausal patients (HR = 2.49; 95%CI 1.90-3.26; p= 4.14 × 10 - 11) with mortality linearly increasing with age (HR = 1.05 per year; 95%CI 1.04-1.07; p= 2 × 10 - 6), in patients diagnosed with non-high-grade serous OC (HR = 0.44; 95%CI 0.32-0.60; p= 1.95 × 10 - 7) and in patients carrying a gBRCA1 pathogenic variant (HR = 0.65; 95%CI 0.48-0.87; p= 4.53 × 10 - 3). The multivariate analysis interrogating the effect of PRDM1 rs2185379 with other significant prognostic factors revealed marginal association of PRDM1 rs2185379 with worse survival in postmenopausal women (HR = 1.54; 95%CI 1.01-2.38; p= 0.046). Unlike age at diagnosis, OC histology or gBRCA1 status, rs2185379 in PRDM1 is unlikely a marker of long-term survival in patients with advance OC.

Significance of Runt-related transcription factor 1 and Notch1 expression in non-small-cell lung cancer: involvement in epithelial-mesenchymal transition and epidermal growth factor receptor-tyrosine kinase inhibitor therapy resistance

Objective One of the main obstacles to treating patients with non-small-cell lung cancers (NSCLC) is the emergence of drug resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Aim To investigate the prognostic relevance of Runt-related transcription factor 1 (RUNX1) and Notch1 in NSCLC and to evaluate their potential involvement in induction of epithelial-mesenchymal transition and resistance to EGFR-TKI therapy. Materials and methods Immunohistochemical study of RUNX1, Notch1, E-cadherin, and hypoxia-inducible factor 1α (HIF-1α) was conducted upon 83 cases diagnosed as NSCLC. The research was conducted in the departments of pathology, chest, and medical oncology of the Faculty of Medicine, Benha University. Results A significant relation was found between RUNX1 and sex (P=0.001), smoking history (P=0.002), and tumor grade (P=0.002). High RUNX1 expression was associated with poor OS and DFS (P=0.003 and 0.005), respectively. Cases with positive Notch1 expression were significantly associated with tumor grade (P=0.005) and tumor stage (P=0.024). A significant association was detected between Notch1 expression and poor OS and DFS (P=0.025 and 0.011), respectively. A statistically significant correlation was found between RUNX1 and Notch1 expressions (P=0.040). Moreover, high RUNX1 and positive Notch1 expressions were significantly associated with negative E-cadherin and positive HIF-1α expressions. Resistance against EGFR–TKI therapy was significantly associated with high RUNX1, positive Notch1, negative E-cadherin, and positive HIF-1α expressions, in EGFR-mutated cases. Conclusions RUNX1 and Notch1 may be involved in therapy resistance through the induction of epithelial–mesenchymal transition and may serve as prognostic markers in patients with NSCLC.

Role of Mean Platelet Volume (MPV) as a Prognostic Marker in Patients with Acute Kidney Injury

ABSTRACT This study aimed to investigate the prognostic significance of mean platelet volume (MPV) in 50 AKI patients. Blood samples were collected according to KDIGO guidelines, and complete blood counts, including MPV, were analyzed. Significant differences in MPV were observed among patients who recovered with or without dialysis and those who expired. A statistically significant difference was present in between the mean platelet count of patients recovered without dialysis, recovered with dialysis, and the expired patients. The Area Under Curve (AUC) for MPV scores was as high as 0.842. Indicating that in up to 84% of the pairs (death-survival) the models correctly estimated that the probability of survival was higher than that of death. MPV had an optimum cutoff point of score value <9.60 with a sensitivity of 80% and specificity of 91.11%. These findings suggested that MPV could serve as a cost-effective and superior tool to creatinine in early AKI detection.

The Value of Preoperative C-Reactive Protein to Albumin Ratio as a Prognostic Biomarker in Colon Cancer Patients.

Inflammatory acute phase proteins have been reported to play a crucial role in cancer progression. Various hematologic and inflammatory markers and scores, such as the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammation score (SIS), prognostic nutritional index (PNI), Glasgow prognostic score, and, more recently, the Naples prognostic score, have been reported as significant prognostic markers. The aim of this prospective study was to evaluate the prognostic significance of the C reactive protein-to-albumin ratio (CAR) in patients with colon cancer. Materials and Methods: We conducted a prospective observational study on a series of patients who underwent curative surgery for colon cancer. The C reactive protein-to-albumin ratio was determined preoperatively, and we evaluated the correlations between the CAR and various clinical and pathological parameters, as well as the correlation with Overall and Relapse-free survival. Furthermore, we compared the accuracy of the CAR with that of the Naples score. Results: One hundred and ten patients were included in the study. We set 0.4927 as the cut-off value for the CAR according to a receiver operating characteristic curve analysis. Based on the cut-off value, patients were divided into a low CAR group and a high CAR group. The preoperative CAR exhibited statistically significant correlation with tumor volume, T and N stage, number of positive lymph nodes, and grade of tumor differentiation. We also demonstrated a positive correlation between high CAR values and a higher Naples score (p = 0.0005), even when a subgroup analysis was performed for each group individually. Conclusions: The preoperative CAR is a useful prognostic marker in patients with colon cancer. These results may help to design strategies to personalize targeted management approaches among colon cancer patients.

Association between the advanced lung cancer inflammation index and all-cause and cardiovascular mortality in patients with RA: Insights from NHANES data analysis

BackgroundRheumatoid arthritis (RA) is associated with significant mortality, which is primarily due to cardiovascular complications. Despite advancements in RA treatment, mortality rates remain high, highlighting the need for reliable prognostic markers. The advanced lung cancer inflammation index (ALI), which integrates inflammatory and nutritional biomarkers, has shown promise in predicting outcomes in various medical conditions. However, its role in RA prognosis remains unclear. MethodsThis study aimed to investigate the associations between the ALI and all-cause mortality, as well as cardiovascular mortality, in RA patients using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1568 RA patients were included, and the ALI was calculated using body mass index (BMI), serum ALB, and the neutrophil-to-lymphocyte ratio. Comprehensive demographic, lifestyle, and metabolic data from the NHANES enabled adjustments for potential confounders. Multivariate Cox regression and sensitivity analyses were conducted to assess the associations between the ALI and mortality outcomes. ResultsOur findings demonstrate an inverse association between the ALI and both all-cause and cardiovascular mortality in RA patients. Furthermore, a nonlinear relationship was observed, with mortality risk increasing significantly below a certain ALI threshold. Stratified analyses revealed a protective effect of the ALI across various demographic and clinical subgroups, underscoring its potential as a prognostic marker in patients with RA. ConclusionThe ALI holds promise as a valuable prognostic marker for identifying high-risk individuals and guiding personalized management strategies for patients with RA. However, further validation in prospective studies is warranted to confirm its clinical utility. Nonetheless, the potential implications of the ALI for improving the prognosis of patients with RA underscore the importance of its continued investigation in clinical practice.

Troponin-I as a Prognostic Marker in Patients with Coronavirus Disease 2019: Insights from a Single-center Investigation

Background: Troponin-I is conventionally correlated with myocardial injury, but its relevance in assessing the severity of coronavirus disease 2019 (COVID-19) and its implications for patient management remains an area of ongoing investigation. This study was designed to assess the correlation between troponin-I levels and the disease severity among patients with COVID-19. Materials and Methods: This retrospective study was conducted at a tertiary care center in India between April 2020 and November 2021. The patients with reverse transcription-polymerase chain reaction who tested positive for COVID-19 infection, and who underwent troponin-I examination at presentation were included in the study. A comparison of baseline clinical characteristics among patients who survived and who did not survive post-COVID-19 was done, and risk factors associated with mortality among hospitalized patients were analyzed. Results: A total of 1673 patients were enrolled in this study. Of these, 1431 patients survived, and 242 patients did not survive post-COVID-19. The mean age of the patients with troponin-I levels ≤0.06 ng/ml was 49.66 ± 17.88 years and that of patients with troponin-I levels >0.06 ng/ml was 60.13 ± 20.04 years. The nonsurvival rate was high in patients aged >50 years compared to the patients aged ≤50 years (81.4% vs. 18.6%; P < 0.001). The mortality rate was high in patients with troponin-I levels >0.06 ng/ml compared to the patients with troponin-I levels ≤0.06 ng/ml (51.7% vs. 48.3%; P < 0.001). Breathlessness (odds ratio [OR]: 26.901; P < 0.001), cut-off troponin-I levels (OR: 8.246; P < 0.001), and other comorbidities (OR: 8.246; P < 0.001) were independently correlated with mortality among hospitalized patients with COVID-19. Conclusion: This study demonstrated that elevated troponin-I level at presentation was associated with disease severity and increased mortality in patients with COVID-19.

BRCA1, BRCA2 and PALB2 mRNA Expression as Prognostic Markers in Patients with Early Breast Cancer.

We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis. The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050). According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression.

Tumor budding is a meaningful prognostic marker in patients with hepatocellular carcinoma after curative hepatectomy

AbstractAimTumor budding (TB) has excellent prognostic value in many solid tumors, but there is little research on it in hepatocellular carcinoma (HCC). This study assessed the prognostic value of TB in patients with HCC who received hepatectomy.MethodsThis retrospective study included 210 patients with HCC who received curative hepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University, between 2016 and 2018. TB was evaluated on hematoxylin‐ and eosin‐stained slides according to the criteria established by the 2016 International Tumor Budding Consensus Conference. t‐tests, Chi‐squared tests, and rank‐sum tests were used to correlate the extent of TB with clinicopathological parameters. Prognostic analysis was performed using Cox regression models and the Kaplan–Meier method.ResultsThe positive detection rate of TB was 45.2% (95/210) in 210 patients with HCC. Patients positive for TB always exhibit lower tumor differentiation, higher hepatitis B virus DNA levels, and more severe liver fibrosis. Multivariate Cox analysis identified TB (hazard ratio [HR]: 2.232, 95% confidence interval [CI]: 1.479–3.368, p &lt; 0.001) as an independent prognostic factor for patients' recurrence‐free survival (RFS), similar to tumor size (HR: 1.070, 95% CI: 1.070–1.142, p = 0.042) and satellite nodule (HR: 2.266, 95% CI: 1.298–3.956, p = 0.004). Kaplan–Meier analysis also demonstrated that TB‐positive patients had a significantly worse RFS. Interestingly, subgroup analysis revealed that among HCC patients with negative microvascular invasion (MVI), TB was also strongly associated with RFS (HR: 3.206, 95% CI: 1.667–6.168, p &lt; 0.001). These findings suggest that TB may serve as a supplemental prognostic biomarker for HCC‐negative MVI.ConclusionsTB is an adverse prognostic biomarker for HCC, particularly in patients negative for MVI. TB evaluation should be considered in the postoperative pathological examination of HCC in clinical practice.

Pan-immune-inflammation value: a new prognostic index in operative laryngeal and pharyngeal carcinomas.

This study aimed to further evaluate the potential value of Pan-Immune-Inflammation Value (PIV) as a prognostic marker in patients with laryngeal and pharyngeal tumors. A total of 545 patients with laryngeal and pharyngeal tumors who underwent surgery at Qilu Hospital of Shandong University were included. We determined the optimal cutoff of PIV and divided the patients into two groups. The relationship between PIV and clinicopathological features was explored by the chi-square test and the Mann-Whitney U test. Survival analysis and Cox regression analysis were used to evaluate the relationship between PIV and overall survival (OS) and disease-free survival (DFS). We also compared the prognostic predictive value of PIV with other inflammation-related markers. Finally, we developed a simple scoring prediction model based on several independent prognostic parameters. We found that PIV was statistically associated with clinicopathological features such as tumor stage (p < 0.001), node stage (p = 0.001), postoperative chemotherapy (p = 0.026), and vascular thrombosis (p = 0.027). Survival analysis demonstrated a significant correlation between elevated PIV and reduced OS and DFS (p < 0.0001). Multivariate Cox regression analysis further confirmed PIV as a prognostic indicator (HR 2.507; 95% CI 1.343-4.681; p = 0.004), which is superior to SII, NLR, MLR and PLR. Three of the independent prognostic factors screened by multivariate Cox regression analysis were selected to be used to create a scoring system with a concordance index of 0.756. Elevated PIV is associated with poor prognosis in patients with laryngeal and pharyngeal tumors, suggesting that PIV may be an important adjunctive indicator for assessing patient prognosis. Registration number: KYLL-202307-001, date: July 2023.

The controlling nutritional status score as a predictor of survival in hematological malignancies: a systematic review and meta-analysis

ObjectiveThe controlling nutritional status score (CONUT) has been widely used for ascertaining the prognosis of various cancers. However, its use in patients with hematological malignancies remains unclear. This review examined evidence on the utility of CONUT as a prognostic marker for patients with hematological malignancies.MethodsAll cohort studies that examined the association between CONUT and outcomes of hematological malignancies and were published on the databases of Embase, Scopus, CENTRAL, Web of Science, and PubMed were searched from the inception of the databases to 30 January 2024. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS).ResultsA total of 23 studies were available for review. A meta-analysis of 22 studies showed that high CONUT was significantly associated with poor OS in patients with hematological malignancies (HR: 1.95 95% CI: 1.62, 2.35 I2 = 89%). The results remained unchanged on sensitivity and subgroup analyses based on study location, sample size, diagnosis, CONUT cutoff, and the Newcastle–Ottawa Scale score. Only six studies reported data on PFS, and the pooled analysis found that high CONUT was a significant marker for poor PFS in patients with hematological malignancies [hazards ratio (HR): 1.64 95% CI: 1.21, 2.20 I2 = 70%]. These results, too, maintained significance in the sensitivity analysis.ConclusionCONUT is an independent predictor of poor OS in patients with hematological malignancies. The results appear to be valid across different cancer types and with different CONUT cutoffs. Scarce data also suggest that CONUT could predict PFS.

Plasma presepsin for mortality prediction in patients with sepsis-associated acute kidney injury requiring continuous kidney replacement therapy.

The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). This study analyzed the utility of plasma presepsin values in predicting mortality in patients with AKI requiring CKRT, particularly those with sepsis-associated AKI. This single-center retrospective study included 57 patients who underwent CKRT, with plasma presepsin measurements, from April 2022 to March 2023; 35 had sepsis-associated AKI. The predictive values of plasma presepsin, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, for 28-day mortality were analyzed using receiver operating characteristic curves. Multivariate Cox regression analysis was performed to identify risk factors for 28-day mortality in the sepsis-associated AKI subgroup. Overall, plasma presepsin showed a lower area under the curve value (0.636; 95% confidence interval [CI], 0.491-0.781) than the APACHE II (0.663; 95% CI, 0.521-0.804) and SOFA (0.731; 95% CI, 0.599-0.863) scores did. However, in sepsis-associated AKI, the area under the curve increased to 0.799 (95% CI, 0.653-0.946), which was higher than that of the APACHE II (0.638; 95% CI, 0.450-0.826) and SOFA (0.697; 95% CI, 0.519-0.875) scores. In the multivariate Cox regression analysis, a high presepsin level was an independent risk factor for 28-day mortality in sepsis-associated AKI (hazard ratio, 3.437; p = 0.03). Presepsin is a potential prognostic marker in patients with sepsis-associated AKI requiring CKRT.

Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review.

In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.

Value of zonulin as a diagnostic and prognostic marker in different degrees of nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is a group of hepatic disorders ranging between simple form of accumulation of fat in hepatocytes (hepatic steatosis) and inflammation of liver internal tissues and injury of hepatocytes that is known as nonalcoholic steatohepatitis (NASH) with increasing levels of fibrosis and cirrhosis and hepatocellular carcinoma (HCC). The composition of one’s gut microbiota has a role in both the onset and progression of chronic liver disorders. One indicator of intestinal permeability is zonulin. In this study, we aimed to detect the value of zonulin as a diagnostic and prognostic marker in patients with different degrees of nonalcoholic fatty liver disease (steatosis, steatohepatitis, cirrhosis).This case–control study was conducted on 60 subjects in Gastroenterology and Bariatric Surgery Departments at Ain Shams University Hospitals who were divided into 3 groups: Group A: 20 patients underwent bariatric surgery and have mild NASH, Group B: 20 patients underwent bariatric surgery and have moderate-to-severe NASH, and Group C: 20 healthy controls, during a period 1 of year.ResultsThere was high statistically significant difference between the studied groups; as regard zonulin concentration, zonulin showed high diagnostic accuracy in diagnosis of NASH among hepatic patients with total accuracy of 81.7%, sensitivity of 72.5%, and specificity of 100.ConclusionSerum zonulin levels increase with steatosis severity in patients with NAFLD. This explains the high diagnostic accuracy of zonulin in diagnosis and prognosis of NASH among patients.

Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.

e16197 Background: CARES-310 (NCT03764293) evaluated the combination of the PD-1 inhibitor, cam, and the VEGFR-2 tyrosine kinase inhibitor, rivo, compared to sorafenib (sor) for the treatment of 543 patients (pts) with uHCC. Cam + rivo significantly improved mOS (22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p &lt; 0.0001) and mPFS (5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.54 [95% CI 0.44-0.67]; one-sided p &lt; 0.0001) compared to sor. The most common (≥20%) grade ≥3 treatment-related adverse events (TRAEs) for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. An elevated level of inflammation, including NLR and PLR, have been associated with poor survival outcomes in pts with HCC (Lin S, et al. Trans Cancer Res. 2021). Here, we present a subgroup analysis of the CARES-310 trial evaluating the impact of baseline (BL) NLR and PLR status on pt outcomes. Methods: The subgroup of pts treated with cam+rivo and BL NLR &lt; 5 or ≥5 and PLR &lt; 300 or ≥300 were evaluated for mOS, mPFS, overall response rate (ORR), disease control rate (DCR), and safety. Results: Of 272 pts treated with cam+rivo, 64.3% of pts had extrahepatic spread, median AFP was 84.1 ng/mL, 86.8% were Child-Pugh (CP) class A5, 13.2% were CP class A6, 73.5% were ALBI grade 1, 26.5% were ALBI grade 2. Additionally, 249 pts had NLR &lt; 5, 10 pts had NLR ≥5, 252 pts had PLR &lt; 300, and 7 pts had PLR ≥300. Pts with BL NLR &lt; 5 and PLR &lt; 300 demonstrated improved outcomes in mOS, mPFS, ORR, and DCR vs pts with BL NLR ≥5 and PLR ≥300 (Table). Rates of any grade TRAEs and grade ≥ 3 TRAEs were comparable between pts with BL NLR &lt; 5 and ≥5 and PLR &lt; 300 and ≥300 (Table). Conclusions: These results suggest that NLR and PLR may serve as a prognostic marker in patients with uHCC, but larger studies are needed to validate these findings. Clinical trial information: NCT03764293 . [Table: see text]

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as an Early Prognostic Marker in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis.

Presently, ovarian cancer remains the leading cause of death in gynecological malignancies. The survival rate of these patients is low, which might be caused by early metastases and delayed diagnosis. Therefore, it is crucial to investigate novel practical markers that provide early prognostic value which helps construct individualized treatment. A thorough investigation of the neutrophil-lymphocyte ratio (NLR) and lymphocyte ratio (PLR) in ovarian cancer patients was conducted using article selection from PubMed, Cochrane, Science Direct, and Google Scholar databases. The outcomes and hazard ratio (HR) were obtained using Review Manager 5.4, and the 95% Confidence Interval (CI) result was calculated. The chief endpoints of interest in this study include overall survival (OS) and progression-free survival (PFS). Sixteen studies with 3,862 patients were included with a mean age of 50.6 years and a mean follow-up of 45.84 months. Multivariate studies demonstrated that a higher NLR is associated with worse PFS and OS, HR 1.35;95% CI [1.05-1.74] and HR 1.46; 95% CI [1.16-1.83] respectively. Similar results are observed with PLR and poorer PFS and OS, HR 1.62; 95% CI [1.09-2.43] and HR 1.66; 95% CI [1.12-2.46]. Pre-treatment PLR and NLR were found to be prognostic factors in determining PFS and OS in ovarian cancer. High values in pre-treatment PLR and NLR may indicate worse clinical outcomes.

SLC7A11 and the glutathione pathway as novel prognostic markers in resectable pancreatic ductal adenocarcinoma: A metabolomics study of clinical specimens

Background/objectivesDespite the poor prognosis associated with pancreatic ductal adenocarcinoma (PDAC), there remains a lack of clarity regarding the metabolic pathways and their significant impact on its phenotype. Therefore, we aimed to utilize metabolomics to capture changes in clinical PDAC tissues and elucidate the significant metabolic pathways close to its phenotypes. MethodsThis basic research was retrospectively validated using database research, immunohistochemistry, and protein analysis based on the findings obtained from metabolomics using clinical tissues collected from prospectively registered patients with PDAC. mRNA expression analysis using a database and protein analysis using archived clinical specimens was performed to validate the candidate pathways identified using metabolomics. Between-group comparisons were analyzed using paired t-tests and log-rank test, and Kaplan–Meier curves illustrated survival times. ResultsPatients subjected to metabolomics revealed a significant increase in glutathione disulfide levels in PDAC tissues when compared to normal pancreatic tissues. The Cancer Genome Atlas database analysis revealed significant changes in glutathione pathway-related mRNAs in PDAC compared to that in the normal pancreas. Protein analysis of previously resected specimens demonstrated a significant increase in SLC7A11 expression in PDAC tissues. The abundance ratio of SLC7A11 isoforms was associated with the post-operative prognosis in resectable PDAC. ConclusionGlutathione disulfide levels were significantly increased in clinical PDAC metabolomics. Additionally, increased mRNA and protein expression in SLC7A11 was observed in PDAC. Furthermore, the SLC7A11 isoform abundance ratio may be a valuable prognostic marker in patients with resectable PDAC.

Preoperative and postoperative platelet-lymphocyte ratio as a prognostic marker for patients with soft tissue sarcoma treated with curative resection.

e23568 Background: In cancer development and progression, systemic inflammation has been implicated. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. In this study, we explored the prognostic relevance of initial and postoperative systemic inflammatory markers (neutrophil -lymphocyte ratio, platelet -lymphocyte ratio) on relapse-free survival (RFS) and overall survival (OS) in patients with soft -tissue sarcoma (STS) who underwent curative resection. Methods: We included a total of 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital (Daegu, Korea,) between 2004 and 2018. Kaplan-Meier curves and RFS and OS were calculated using multivariate Cox proportional models. Results: The median age of the patients was 55 years (range 27 - 86) and the ratio of male-to-female ratio was approximately 1:1. A total of 67 (75.3%) patients demonstrated a high initial neutrophil-lymphocyte ratio(NLR) (≥4.1) and 65 (75.3%) showed a high initial platelet-lymphocyte ratio(PLR) (≥231). After curative resection, the number of patients with high NLR and PLR was 16(18.0%) and 17 (29.3%). In both the NLR and PLR groups, including the postoperative NLR and postoperative PLR subgroups, no significant differences were observed in terms of age, sex, histologic type, tumor site, tumor size, tumor depth, or American Joint Committee on Cancer staging when stratified into high and low subgroups. In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (hazard ratio[HR]: 2.120; 95% confidence interval[CI]: 1.021 - 4.883, p = 0.017) and OS (HR: 5.073; 95% CI: 1.731 - 14.87, p = 0.003). Patients with a high PLR (PLR &gt; 231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was significantly associated with a decreased RFS (HR: 3.921; 95% CI: 1.738 - 8.845, p = 0.001) and OS (HR: 5.702; 95% CI: 1.099 -29.576, p = 0.038). Conclusions: The present results suggest that the preoperative and postoperative PLR ratio can be used as a cost- effective prognostic marker for oncologic outcomes in patients with STS who underwent surgery.

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma.

We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

Prognostic significance of preoperative to postoperative serum carcinoembryonic antigen ratio after lobectomy for lung adenocarcinoma.

Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2ng/ml (n = 28). Patients with postoperative CEA > 6.2ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.