Preoperative Immune Cell Dysregulation Accompanies Ovarian Cancer Patients into the Postoperative Period
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ABSTRACT:
SUBMITTER: Ulevicius J
PROVIDER: S-EPMC11240929 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:The molecular basis for psychosocial-distress mediated immune-dysregulation is not well understood. The purpose of this study was to determine whether peripheral blood mononuclear cell (PBMC) epigenetic pattern associates with this form of immune dysregulation. Women newly diagnosed with early stage breast cancer were enrolled into the study and psychosocial, immunological and epigenetic assessments were made at diagnosis and four months later, after completion of cancer treatment. At diagnosis women reported increased perceived stress, anxiety, and mood disturbance and the PBMC of these women exhibited reduced natural killer cell activity and reduced production of interferon gamma, which contrasted with results, obtained after completion of treatment. At the epigenetic level, a PBMC subset derived from women at diagnosis exhibited a distinct epigenetic pattern, with reduced nuclear acetylation of histone residues H4-K8 and H4-K12, as well as reduced phosphorylation of H3-S10, when compared to similar cells derived after the completion of treatment. Natural killer cell activity and interferon-gamma production were associated with nuclear acetylation and phosphorylation status of these histone residues. These findings demonstrate associations among nuclear epigenetic pattern and the immune dysregulation that accompanies psychosocial distress.
| S-EPMC3079772 | biostudies-literature
Project description:BackgroundWe investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens.MethodsBetween July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures.ResultsThe study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042).ConclusionsctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.
| S-EPMC10498401 | biostudies-literature
Project description:BackgroundOvarian cancer (OC) is a highly aggressive and often fatal disease that frequently goes undetected until it has already metastasized. The classic treatment for OC involves surgery followed by chemotherapy. However, despite the effectiveness of surgery, relapse is still a common occurrence. Unfortunately, there is currently no ideal predictive model for the progression and drug sensitivity of postoperative OC patients. Cell death patterns play an important role in tumor progression. So we aimed to investigate their potential to be used as indicators of postoperative OC prognosis and drug sensitivity.MethodsA total of 12 programmed cell death (PCD) patterns were employed to construct novel classification and prognosis model. Bulk transcriptome, genomics, and clinical information were collected from The Cancer Genome Atlas (TCGA) Program-OV, GSE9891, GSE26712, GSE49997 and GSE63885. In addition, single-cell transcriptome data GSE210347 were procured from the Gene Expression Omnibus (GEO) database for subsequent analysis.ResultsIn this study, a novel PCD classification has been employed to phenotype postoperative OC patients, revealing that patients in cluster 1 exhibited heightened sensitivity to immune-based therapies combined with high expression of chemokines, interleukins, interferons, and checkpoints. Meanwhile, a programmed cell death index (PCDI) was established using an 8-gene signature with the help of a machine learning algorithm. The patients with high-PCDI had a worse prognosis after surgery in OC. In addition, we also found that patients with low PCDI patients may exhibit sensitivity to immunotherapy, while those with high PCDI patients may display increased responsiveness to tyrosine kinase inhibitors.ConclusionsThis study provides a novel PCD model and nomogram that can effectively predict the clinical prognosis and drug sensitivity of OC patients post-surgery.
| S-EPMC11651737 | biostudies-literature
Project description:IntroductionPatient falls in the hospital lead to adverse outcomes and impaired quality of life. Older adults with cancer who are frail may be at heightened risk of falls in the postoperative period. We sought to evaluate the association between degree of preoperative frailty and risk of inpatient postoperative falls and other outcomes among older adults with cancer.Materials and methodsWe identified 7,661 patients aged 65 years or older who underwent elective cancer surgery from 2014 to 2020, had a hospital stay of ≥1 day, and had Memorial Sloan Kettering-Frailty Index (MSK-FI) data to allow assessment of frailty. Univariable logistic regression analysis was performed to evaluate the association between frailty and falls. Multivariable logistic regression analysis was performed to evaluate the composite outcome of 30-day readmission or 90-day death, with frailty, falls, and the interaction between frailty and falls as predictors; the analysis was adjusted for age, sex, race, and preoperative albumin level.ResultsIn total, 7,661 patients were included in the analysis. Seventy-one (0.9%) had a fall, of whom eight (11%) were readmitted to the hospital within 30 days and seven (10%) died within 90 days. Higher MSK-FI score was associated with higher risk of falls (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.21-1.59]). The risk of falls for a patient with an MSK-FI score of 1 was 0.6%, compared with 1.7% for a patient with an MSK-FI score of 4. Poor outcome was associated with frailty (OR, 1.07 [95% CI, 1.02-1.13]) but not with falls (OR, 1.17 [95% CI, 0.57-2.22]).DiscussionPreoperative frailty is associated with risk of inpatient postoperative falls and with other adverse outcomes after surgery among older adults with cancer. Screening for frailty in the preoperative setting would enable healthcare institutions to implement interventions aimed at reducing the incidence of inpatient postoperative falls to reduce fall-related adverse events.
| S-EPMC11881942 | biostudies-literature
Project description:BackgroundUp to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown.MethodsSera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2-3 weeks and after 6 weeks and analysed for correlation with the development of irAEs.ResultsOf the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs.ConclusionsPatients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.
| S-EPMC6325132 | biostudies-literature
Project description: Not available
| S-EPMC10778568 | biostudies-literature
Project description:BackgroundThis study aimed to evaluate the predictive value of Prognostic Nutritional Index (PNI), Systemic Immunoinflammatory Index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with epithelial ovarian cancer ( EOC). Also, to explore the predictive value of a new scoring system combining PNI and SII (coPNI-SII) in patients with EOC.MethodsIn this study, 154 patients with EOC were analyzed and classified according to the best cut-off values for SII, PNI, PLR, and NLR. Spearman's rank correlation was used to analyze the correlation of variables. The Kaplan-Meier survival curve and log-rank test were used to investigate the relationship between inflammatory indicators and overall survival (OS), which was then followed by a multivariate Cox proportional hazards model. All patients were categorized into three groups based on PNI-SII scores. The coPNI-SII score ranged from 1 to 3 as follows: score of 1, high PNI (≥ 48.98) and low SII(< 998.87); score of 2, high PNI and high SII or low PNI and low SII; score of 3, low PNI and high SII. To assess the prognostic value of coPNI-SII in patients with EOC.ResultsThe areas under the ROC curves for SII, PNI, PLR, NLR, and coPNI-SII were 0.814, 0.814, 0.780, 0.769, and 0.860, respectively. The optimal cut-off values for SII, PNI, PLR, and NLR were 998.87, 48.98, 217.63, and 2.61, respectively. The Kaplan-Meier analysis showed that the OS of the patients in the high PNI group, low SII group, low NLR group, and low PLR group was significantly higher than that of the patients in the low PNI group, high SII group,high NLR group, and high PLR group (p < 0.01). SII (P = 0.034), PNI (P = 0.013), FIGO staging (P = 0.009), ascites (P = 0.003), CA199 (P = 0.003), HE4 (P = 0.028), residual lesions (P = 0.022), and margins of incision (P < 0.001) were found to be significant prognostic indicators of OS by multifactorial Cox regression analysis. There was a significant inverse relationship between the PNI and SII (r = -0.484; P < 0.01). EOC patients with a coPNI-SII score of 1 had a higher 5-year OS rate (P < 0.05) than EOC patients with a coPNI-SII score of 2 or 3. When taking into account both the SII and PNI, the predictive value rose.ConclusionInterestingly, we found that low preoperative PNI and high SII were strong indicators of poor prognosis in patients with EOC. The combination of SII and PNI can enhance the accuracy of prognosis.
| S-EPMC11887369 | biostudies-literature
Project description:Cisplatin-based adjuvant chemotherapy remains the standard of care for patients with resected stage II or III non-small-cell lung cancer. However, biomarker-informed clinical trials are starting to push the management of early-stage lung cancer beyond cytotoxic chemotherapy. This review explores recent and ongoing studies focused on improving cytotoxic chemotherapy and incorporating targeted and immunotherapies in the management of early-stage, resectable lung cancer. Adjuvant osimertinib for patients with EGFR-mutant tumors, preoperative chemoimmunotherapy, and adjuvant immunotherapy could improve outcomes for selected patients with resectable lung cancer, and ongoing or planned studies leveraging biomarkers, immunotherapy, and targeted therapy may further improve survival. We also discuss the unique barriers associated with clinical trials of early-stage lung cancer and the need for innovative trial designs to overcome these challenges.
| S-EPMC8853628 | biostudies-literature
Project description:BACKGROUND:AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC). METHODS:Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed. RESULTS:The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6?years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p?=?0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p?=?0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. CONCLUSION:Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.
| S-EPMC7659101 | biostudies-literature
Project description:BackgroundAccompanying co-morbidities in patients with ovarian cancer are of major relevance for scheduling debulking surgery, especially in the anesthesiological consultations. Aim of this study was to evaluate the impact of co-morbidities and patient characteristics on postoperative complications.MethodsPatients undergoing maximal cytoreductive surgery were prospectively enrolled from October 2015 to January 2017. Various variables were recorded, such as the Charlson comorbidity index, Eastern cooperative oncology group scale of performance status (ECOG PS) and the American society of anesthesiologists physical status classification system (ASA PS). Surgical complications were graded using the Clavien-Dindo criteria. Logistic regression models were used to analyze risk factors for severe postoperative complications.ResultsOf 106 enrolled patients, 19 (17.9%) developed severe postoperative complications grade ≥ IIIb according to Clavien-Dindo criteria. In the multivariable regression analysis impaired (ECOG PS) > 1 (odds ratio OR) 13.34, 95% confidence interval (CI) 1.74-102.30, p = 0.01), body mass index (BMI) > 25 kg/m2 (OR 10.48, 95% CI 2.38-46.02, p = 0.002) along with the use of intraoperative norepinephrine > 0.11 µg/kg/min (OR 4.69, 95% CI 1.13-19.46, p = 0.03) and intraoperative fresh frozen plasma (FFP) > 17 units (OR 4.11, 95% CI 1.12-15.14, p = 0.03) appeared as significant predictors of severe postoperative complications.ConclusionWe demonstrated that neither the presence of a certain comorbidity nor the summation of the co-morbidities were associated with adverse outcome. Patient characteristics, such as ECOG PS > 1 and obesity (BMI > 25 kg/m2), are highly predictive factors for severe postoperative complications. The analysis of intraoperative data showed that the need for more than > 0.11 µg/kg/min of norepinephrine and transfusions of FFPs more than 17 units were strongly associated with severe postoperative complications.
| S-EPMC8490255 | biostudies-literature