Survival Outcomes In Patients Research Articles

Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma.

Historically, management of relapsed or refractory (R/R) Diffuse large B-cell (DLBCL) following first-line chemoimmunotherapy has been second-line chemotherapy, followed by high-dose chemotherapy and consolidative autologous hematopoietic stem cell transplantation (auto-HSCT), resulting in durable remissions in approximately 40% of patients. In 2017, chimeric antigen receptor (CAR) T-cell therapy changed the landscape of treatment for patients with R/R DLBCL, with complete response rates ranging from 40-58% and long-term disease-free survival of >40% in the highest risk subgroups, including patients who relapsed after auto-HSCT. Since that time further studies have demonstrated improved overall response rates (ORRs) and survival outcomes in patients with primary refractory or early-relapse (relapse 50% of patients will relapse in the post-CAR T-cell setting. In the past two years, two CD20 x CD3 bispecific antibodies (BsAbs) were FDA approved for the treatment of R/R DLBCL after two or more lines of systemic therapy. These BsAbs have demonstrated ORRs exceeding 50% and durable remissions at > 2yrs of follow-up. Additionally, a notable treatment advantage of BsAbs is their ability to be administered in the community setting, making treatment more accessible for patients. The development and advancement of these novel therapies raise questions regarding the ongoing role of HSCT in the management of relapsed and refractory DLBCL and how to best sequence cellular and Bi-specific therapies to optimize patient outcomes.

Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001). Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.

The role of adjuvant chemotherapy after radical surgery in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer: A meta-analysis and systematic review.

This study aims to evaluate the impact of adjuvant chemotherapy (AC) on survival outcomes in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer after surgery. We also seek to identify which patients with pN+ bladder cancer are most likely to benefit from AC after radical cystectomy (RC). We searched databases including Embase, PubMed, Cochrane, and ClinicalTrials.gov to identify relevant literature published in English up to February 2024. We used Stata to compare various parameters. The study has been registered in PROSPERO. A total of 21 studies were analyzed, including 1 randomized controlled trial, 6 prospective studies, and 14 retrospective studies, encompassing 12,888 patients. The meta-analysis showed that for patients with lymph node-positive bladder cancer, the adjuvant chemotherapy (AC) group had higher overall survival (OS) (I2=58.2%, HR 0.69; 95% CI: 0.57-0.83; P=0.019) and recurrence-free survival (RFS) (I2=66.6%, HR 0.71; 95% CI: 0.57-0.89; P=0.006) compared to the radical cystectomy (RC) group. For patients with pT3 and pT4a bladder cancer, the AC group had higher overall survival (OS) (I2=57.3%, HR 0.77; 95% CI: 0.67-0.89; P=0.022) and cancer-specific survival (CSS) (I2=47.2%, HR 0.75; 95% CI: 0.64-0.88; P=0.0048) compared to the RC group. At the same time, according to the different chemotherapy regimens, we divided the cisplatin-based chemotherapy regimen and carboplatin based chemotherapy or other regimens into two subgroups for analysis, and found that the OS (I2=41.4%, HR 0.64; 95%CI: 0.51~0.80; P=0.000) was better than carboplatin and other chemotherapy regimens (I2=64.1%, HR 0.77; 95%CI: 069~0.86; P=0.000); Lymph node density (LND) was found to be an independent predictor of overall survival (HR=1.6; 95% CI: 1.31-1.95; P=0.0000). This study found that postoperative adjuvant chemotherapy (AC) improves overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) in patients with pT3, pT4a, It was also confirmed that cisplatin-based chemotherapy regimen was more beneficial for patients with bladder cancer; and lymph node-positive bladder cancer. Additionally, our analysis revealed that patients with lymph node-positive bladder cancer benefit more from postoperative AC. It was further demonstrated that cisplatin-based chemotherapy regimens are more beneficial than other regimens for patients with locally advanced bladder cancer.

Impact of low sodium values on survival outcomes of patients with cancer receiving immune checkpoint inhibitors.

Background: Low serum sodium affects cancer prognosis, but its impact on immunotherapy is unclear. Objective: Assessing the association of pre- and post-ICI treatment sodium levels with survival. Methods: We retrospectively analyzed patients receiving ICI in January 2012-December 2023, collecting serum sodium levels at treatment initiation and 4weeks post-ICI, with overall survival (OS) as the primary outcome. Results: Low sodium was observed in 125 and 119 patients pre-and post-treatment respectively. Pre-ICI and post-ICI low sodium correlated with decreased OS [10.6 vs. 22.9months (p =0.001) and 11.6 vs. 27.2months (p =0.009)]. Multivariate analysis identified pre-ICI low sodium [HR: 1.685; 95% CI: 1.050-2.705; p =0.031] as an independent risk factor for worse OS. Conclusion: Low baseline serum sodium was an independent risk factor for poor OS in patients treated with ICIs.

Lessons For COVID-19 Era: Impact of Delays in Surgery on Biochemical Recurrence-Free Survival and Adverse Oncological Outcomes in Patients with Prostate Cancer

Lessons For COVID-19 Era: Impact of Delays in Surgery on Biochemical Recurrence-Free Survival and Adverse Oncological Outcomes in Patients with Prostate Cancer

Co-expression of CD44v6 and MMP2 predicts lung metastasis and unfavorable prognosis in osteosarcoma.

Aim: To evaluate the prognostic significance of CD44 variant v6 (CD44v6) and matrix metalloproteinases 2 (MMP2) expression in patients with surgically resected osteosarcoma. Methods: CD44v6 and MMP2 expression were immunohistochemically detected in 113 primary osteosarcoma patients at our institute between 2001 and 2019. Results: Both CD44v6 and MMP2 were independent predictors for metastasis-free and overall survival. An extended predictive range and improved sensitivity were observed when the combined effects of CD44v6 and MMP2 were considered. Specifically, patients with CD44v6+and MMP2+expression were more susceptible to lung metastasis and exhibited the poorest survival rates compared with the other groups. Conclusion: The combination of CD44v6 and MMP2 may serve as a precise prognostic indicator for predicting metastatic progression and survival outcomes in patients with osteosarcoma.

The effect of BMI on survival outcome of breast cancer patients: a systematic review and meta-analysis.

The main goal of the present research is to explore the potential link of body mass index (BMI) with different survival metrics in breast cancer patients. Our aim is to offer the latest and most thorough meta-analysis, assessing the strength and reliability of the connection that BMI has with prognostic indicators in this disease. As of January 2024, we conducted a systematic literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases. Our search aimed to identify studies examining BMI as an exposure factor, with breast cancer patients constituting the study population, and utilizing adjusted hazard ratio (HR) as the data type of interest. The evidence synthesis incorporated a total of 61 eligible articles involving 201,006 patients. Being underweight posed a risk factor for overall survival (OS) in breast cancer patients compared to normal weight (HR 1.15, 95% CI 0.98-1.35; P = 0.08). Overweight or obesity, in comparison to normal weight, was a risk factor for OS (HR 1.18, 95% CI 1.14-1.23; P < 0.00001), disease-free survival (DFS) (HR 1.11, 95% CI 1.08-1.13; P < 0.00001), relapse-free survival (RFS) (HR 1.14, 95% CI 1.06-1.22; P = 0.03), and breast cancer-specific survival (BCSS) (HR 1.18, 95% CI 1.11-1.26; P < 0.00001), but not for progression-free survival (PFS) (HR 0.91, 95% CI 0.76-1.10; P = 0.33). Notably, in subgroup analyses, overweight patients achieved prolonged PFS (HR 0.80, 95% CI 0.64-0.99; P = 0.04), and compared to the obese population, the overweight cohort exhibited a significant difference in OS (HR 1.11, 95% CI 1.05-1.16; P < 0.00001) and DFS (HR 1.06, 95% CI 1.03-1.10; P = 0.0004), with a considerably stronger association. Furthermore, compared to HER- patients, HER + patients exhibited a greater predictive value for OS (HR 1.23, 95% CI 1.10-1.37; P = 0.0004), RFS (HR 1.30, 95% CI 1.03-1.64; P < 0.00001), and DFS (HR 1.10, 95% CI 1.03-1.17; P = 0.003). The results of our meta-analysis reveal a notable association between BMI and various survival measures in breast cancer prognosis. These findings provide a solid basis for predicting breast cancer outcomes and implementing more effective therapeutic approaches.

Oncolytic Viral Therapy in Osteosarcoma

Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring or genetically modified viruses to selectively target and lyse cancer cells and induce a robust immune response against remaining OS cells. Various oncolytic viruses (OVs), such as adenovirus, herpes simplex virus, and measles virus, have demonstrated efficacy in preclinical OS models. Combining OVT with other therapeutics, such as chemotherapy or immunotherapy, may further improve outcomes. Despite these advances, challenges in reliability of preclinical models, safety, delivery, and immune response must be addressed to optimize OVT for clinical use. Future research should focus on refining delivery methods, exploring combination treatments, and clinical trials to ensure OVT’s efficacy and safety for OS. Overall, OVT represents a novel approach with the potential to drastically improve survival outcomes for patients with OS.

Carbon-ion radiotherapy alone vs. standard dose photon radiation with carbon-ion radiotherapy boost for high-grade gliomas: a retrospective study

BackgroundThis study aimed to compare the survival outcome and side effects in patients with primary high-grade glioma (HGG) who received carbon ion radiotherapy (CIRT) alone or as a boost strategy after photon radiation (photon + CIRTboost).Patients and methodsThirty-four (34) patients with histologically confirmed HGG and received CIRT alone or Photon + CIRTboost, with concurrent temozolomide between 2020.03–2023.08 in Wuwei Cancer Hospital & Institute, China were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and acute and late toxicities were analyzed and compared.ResultsEight WHO grade 3 and 26 grade 4 patients were included in the analysis. The median PFS in the CIRT alone and Photon + CIRTboost groups were 15 and 19 months respectively for all HGG cases, and 15 and 17.5 months respectively for grade 4 cases. The median OS in the CIRT alone and Photon + CIRTboost groups were 28 and 31 months respectively for all HGG cases, and 21 and 19 months respectively for grade 4 cases. No significant difference in these survival outcomes was observed between the CIRT alone and Photon + CIRTboost groups. Only grade 1 acute toxicities were observed in CIRT alone and Photon + CIRTboost groups. CIRT alone group had a significantly lower ratio of acute toxicities compared to Photon + CIRTboost (3/18 vs. 9/16, p = 0.03). No significant difference in late toxicities was observed.ConclusionBoth CIRT alone and Photon + CIRTboost with concurrent temozolomide are safe, without significant differences in PFS and OS in HGG patients. It is meaningful to explore whether dose escalation of CIRTboost might improve survival outcomes of HGG patients in future randomized trials.

Plasma SCUBE2 as a novel biomarker associates with survival outcomes in patients with sepsis-associated acute kidney injury

BackgroundThe adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. MethodsBetween January 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan–Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. ResultsAmong the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. ConclusionsIn ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.

Distant lymph node metastasis in differentiated thyroid cancer: A population-based cohort study

BackgroundCervical lymph node metastasis (LNM) is the most common clinical event in patients with differentiated thyroid cancer (DTC). However, the incidence, pattern, treatment, and prognosis of distant LNM are yet to be reported. MethodsDTC patients with distant LNM were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2016 and 2020. Multivariate models and propensity score matching (PSM) were used to account for the effects of covariates. The Kaplan-Meier method was used to evaluate the overall survival (OS) and cancer-specific survival (CSS). A nomogram was established to predict the probability of distant LNM in DTC patients, with calibration and Receiver Operating Characteristic (ROC) curves utilized to validate the nomogram's accuracy. ResultsOf the 42,339 DTC patients screened, 100 (0.24 %) patients presented with distant LNM. Risk factors including age, sex, T stage, N stage, bone metastasis, brain metastasis, and lung metastasis were included in the nomogram to predict the probability of distant LNM. The calibration curve of the nomogram was close to the ideal diagonal line and the area under the curve (AUC) of the ROC curve is 0.953. Distant LNM showed a worse prognosis after adjusting for confounders compared with non-distant LNM (P < 0.05). Remarkably, radioactive iodine (RAI) therapy did not improve the OS and CSS in DTC patients with distant LNM in the overall or PSM cohort. ConclusionsDistant LNM presents as a comparatively rare but grave condition with a substantial negative impact on prognosis in patients with DTC. Identified risk factors of distant LNM are older age, male, advanced T stage and N stage, bone metastasis, brain metastasis, and lung metastasis. Remarkably, the current RAI therapy does not appear to significantly improve the survival outcome of DTC patients with distant LNM.

Efficacy and safety evaluation of frontline immunotherapy combinations in advanced esophageal squamous cell carcinoma: a network meta-analysis highlighting the value of PD-L1 expression positivity scores

IntroductionThe systematic review and network meta-analysis (NMA) consolidate all relevant randomized controlled trials (RCTs) related to initial immunotherapy treatments for advanced esophageal squamous cell carcinoma (ESCC). Our goal is to thoroughly assess the effectiveness and safety of various immunotherapy methods, focusing on overall survival (OS) and progression-free survival (PFS) among patients with advanced ESCC positive for PD-L1.MethodsWe conducted a systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases, covering all records from their inception until January 22, 2024. The inclusion criteria targeted patients with advanced ESCC undergoing first-line immunotherapy or chemotherapy, limiting the study selection to randomized controlled trials (RCTs) exclusively. The study upholds the values of openness, originality, and dependability, as evidenced by its enrollment in the Prospective Register of Systematic Reviews (CRD42024504992).ResultsOur analysis encompasses 7 RCTs, totaling 4688 patients, and evaluates 8 distinct immunotherapy combinations. In advanced ESCC patients irrespective of PD-L1 expression, both sintilimab-chemotherapy and toripalimab-chemotherapy regimens demonstrated comparable OS benefits (HR=0.92, 95% CI: 0.64-1.33). The most pronounced PFS advantages were seen with sintilimab-chemotherapy and camrelizumab-chemotherapy as compared to standard chemotherapy (HR=0.56, 95% CI: 0.46-0.58). Notably, camrelizumab-chemotherapy (HR=0.83, 95% CI: 0.59-1.16) and nivolumab-ipilimumab (HR=0.84, 95% CI: 0.60-1.17) demonstrated significant safety profiles over chemotherapy alone. Subgroup analysis based on PD-L1 expression revealed nivolumab-chemotherapy to yield the highest OS benefit (HR=0.54, 95% CI: 0.37-0.79) in ESCC patients with PD-L1 expression ≥1%. Furthermore, camrelizumab-chemotherapy (HR=0.51, 95% CI: 0.39-0.67) exhibited superior PFS benefits. Among patients with PD-L1 expression ≥10%, camrelizumab-chemotherapy (HR=0.52, 95% CI: 0.35-0.78) emerged as the most efficacious in improving OS, while serplulimab-chemotherapy (HR=0.48, 95% CI: 0.34-0.68) was associated with the longest PFS benefit.ConclusionThe integration of immune checkpoint inhibitors (ICIs) with chemotherapy appears to significantly enhance survival outcomes in patients with advanced ESCC compared to chemotherapy alone. Sintilimab-chemotherapy is potentially the optimal regimen for patients without PD-L1 expression. In contrast, nivolumab-chemotherapy and camrelizumab-chemotherapy are likely to offer the best OS and PFS benefits, respectively, in patients with PD-L1 expression ≥1%. Among those with PD-L1 expression ≥10%, camrelizumab-chemotherapy is projected to provide the greatest OS advantage, whereas serplulimab-chemotherapy is anticipated to offer the most prolonged PFS benefit. Since most of the patients in this study originated from Asia, the above findings are more applicable to the Asian population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024504992.

Developing and validating a Modified Cachexia Index to predict the outcomes for colorectal cancer after radical surgery.

It was reported that the cachexia index (CXI: ) was an essential index for predicting the prognosis of tumor patients. However, since for SMI needs to be measured by CT imaging methods and its calculation was inconvenient. Thus, we developed a modified cachexia index (mCXI: ). The purpose of this study was to evaluate the association between mCXI and prognosis in patients with colorectal cancer. An analysis of 215 patients with newly diagnosed colorectal cancer was carried out retrospectively. An optimal cut-off value of mCXI was established by the receiver operating characteristic (ROC) curves for predicting prognosis. Prognostic implications of mCXI were investigated using Kaplan-Meier curves and Cox regression analysis. A comparative assessment of the predictive capacity between mCXI and the CXI was performed using time-dependent receiver operating characteristic analysis. Patients were classified into two groups based on the cut-off value of mCXI: the LOW mCXI group (n = 60) and the HIGH mCXI group (n = 155). The 3-year Overall survival (OS) (76.6% vs 96.7%, p < 0.01) and 3-year Recurrence-free survival (RFS) (68.3% vs 94.1%, p < 0.01) were significantly worse in the LOW mCXI group in contrast to that in the HIGH mCXI group. In Cox multivariate regression analysis, mCXI was an independent prognostic factor for OS (HR = 8.951, 95%CI: 3.105-25.807, <0.01). Moreover, compared with CXI (AUC = 0.723), mCXI (AUC = 0.801) has better predictive efficacy, indicating that mCXI is more suitable for prognostic assessment. The mCXI significantly correlated with survival outcomes for colorectal cancer patients after radical surgery.

Comprehensive analysis of hub genes associated with cisplatin-resistance in ovarian cancer and screening of therapeutic drugs through bioinformatics and experimental validation

BackgroundTo identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation.MethodsGene expression profiles were retrieved from the GEO database. DEGs were identified by comparing gene expression profiles between cisplatin-sensitive and resistant ovarian cancer cell lines. The identified genes were further subjected to GO, KEGG, and PPI network analysis. Potential inhibitors of key genes were identified through methods such as LibDock nuclear molecular docking. In vitro assays and RT-qPCR were performed to assess the expression levels of key genes in ovarian cancer cell lines. The sensitivity of cells to chemotherapy and proliferation of key gene knockout cells were evaluated through CCK8 and Clonogenic assays.ResultsResults showed that 12 genes influenced the chemosensitivity of the ovarian cancer cell line SKOV3, and 9 genes were associated with the prognosis and survival outcomes of ovarian cancer patients. RT-qPCR results revealed NDRG1, CYBRD1, MT2A, CNIH3, DPYSL3, and CARMIL1 were upregulated, whereas ERBB4, ANK3, B2M, LRRTM4, EYA4, and SLIT2 were downregulated in cisplatin-resistant cell lines. NDRG1, CYBRD1, and DPYSL3 knock-down significantly inhibited the proliferation of cisplatin-resistant cell line SKOV3. Finally, photofrin, a small-molecule compound targeting CYBRD1, was identified.ConclusionThis study reveals changes in the expression level of some genes associated with cisplatin-resistant ovarian cancer. In addition, a new small molecule compound was identified for the treatment of cisplatin-resistant ovarian cancer.

Comprehensive analysis of hub genes associated with cisplatin-resistance in ovarian cancer and screening of therapeutic drugs through bioinformatics and experimental validation

BackgroundTo identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation.MethodsGene expression profiles were retrieved from the GEO database. DEGs were identified by comparing gene expression profiles between cisplatin-sensitive and resistant ovarian cancer cell lines. The identified genes were further subjected to GO, KEGG, and PPI network analysis. Potential inhibitors of key genes were identified through methods such as LibDock nuclear molecular docking. In vitro assays and RT-qPCR were performed to assess the expression levels of key genes in ovarian cancer cell lines. The sensitivity of cells to chemotherapy and proliferation of key gene knockout cells were evaluated through CCK8 and Clonogenic assays.ResultsResults showed that 12 genes influenced the chemosensitivity of the ovarian cancer cell line SKOV3, and 9 genes were associated with the prognosis and survival outcomes of ovarian cancer patients. RT-qPCR results revealed NDRG1, CYBRD1, MT2A, CNIH3, DPYSL3, and CARMIL1 were upregulated, whereas ERBB4, ANK3, B2M, LRRTM4, EYA4, and SLIT2 were downregulated in cisplatin-resistant cell lines. NDRG1, CYBRD1, and DPYSL3 knock-down significantly inhibited the proliferation of cisplatin-resistant cell line SKOV3. Finally, photofrin, a small-molecule compound targeting CYBRD1, was identified.ConclusionThis study reveals changes in the expression level of some genes associated with cisplatin-resistant ovarian cancer. In addition, a new small molecule compound was identified for the treatment of cisplatin-resistant ovarian cancer.

Transcriptional phenocopies of deleterious KEAP1 mutations correlate with survival outcomes in lung cancer treated with immunotherapy.

Co-occurring mutations in KEAP1 and STK11KRAS have emerged as determinants of survival outcomes in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. However, these mutational contexts identify a fraction of non-responders to immune checkpoint inhibitors. We hypothesized that KEAP1 wild-type tumors recapitulate the transcriptional footprint of KEAP1 mutations, and that this KEAPness phenotype can determine immune responsiveness with higher precision compared to mutation-based models. The TCGA was used to infer the KEAPness phenotype and explore its immunological correlates at the pan-cancer level. The association between KEAPness and survival outcomes was tested in two independent cohorts of advanced NSCLC patients treated with immunotherapy and profiled by RNA-Seq (SU2C n=153; OAK/POPLAR n=439). The NSCLC TRACERx421 multi-region sequencing study (tumor regions n=947) was used to investigate evolutionary trajectories. KEAPness-dominant tumors represented 50% of all NSCLCs and were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAPness-free cases in independent cohorts of NSCLC patients treated with immunotherapy (SU2C PFS P=0.042, OS P=0.008; OAK/POPLAR PFS P=0.0014, OS P<0.001). Patients with KEAPness tumors had survival outcomes comparable to those with KEAP1-mutant tumors. In the TRACERx421, KEAPness exhibited limited transcriptional intratumoral heterogeneity and immune exclusion, resembling the KEAP1-mutant disease. This phenotypic state occurred across genetically divergent tumors, exhibiting shared and private cancer genes under positive selection when compared to KEAP1-mutant tumors. We identified a KEAPness phenotype across evolutionary divergent tumors. KEAPness outperforms mutation-based classifiers as a biomarker of inferior survival outcomes in NSCLC patients treated with immunotherapy.

Transcriptional phenocopies of deleterious KEAP1 mutations correlate with survival outcomes in lung cancer treated with immunotherapy.

Co-occurring mutations in KEAP1 and STK11KRAS have emerged as determinants of survival outcomes in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. However, these mutational contexts identify a fraction of non-responders to immune checkpoint inhibitors. We hypothesized that KEAP1 wild-type tumors recapitulate the transcriptional footprint of KEAP1 mutations, and that this KEAPness phenotype can determine immune responsiveness with higher precision compared to mutation-based models. The TCGA was used to infer the KEAPness phenotype and explore its immunological correlates at the pan-cancer level. The association between KEAPness and survival outcomes was tested in two independent cohorts of advanced NSCLC patients treated with immunotherapy and profiled by RNA-Seq (SU2C n=153; OAK/POPLAR n=439). The NSCLC TRACERx421 multi-region sequencing study (tumor regions n=947) was used to investigate evolutionary trajectories. KEAPness-dominant tumors represented 50% of all NSCLCs and were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAPness-free cases in independent cohorts of NSCLC patients treated with immunotherapy (SU2C PFS P=0.042, OS P=0.008; OAK/POPLAR PFS P=0.0014, OS P<0.001). Patients with KEAPness tumors had survival outcomes comparable to those with KEAP1-mutant tumors. In the TRACERx421, KEAPness exhibited limited transcriptional intratumoral heterogeneity and immune exclusion, resembling the KEAP1-mutant disease. This phenotypic state occurred across genetically divergent tumors, exhibiting shared and private cancer genes under positive selection when compared to KEAP1-mutant tumors. We identified a KEAPness phenotype across evolutionary divergent tumors. KEAPness outperforms mutation-based classifiers as a biomarker of inferior survival outcomes in NSCLC patients treated with immunotherapy.

Correlation of HCT-ALB, SmtO2, CRT and Lac with renal impairment and prognosis in patients with septic shock

Background: This study investigates the correlation between the difference in hematocrit (HCT) and serum albumin (ALB) levels (HCT-ALB), muscle tissue oxygen saturation (SmtO2), capillary refill time (CRT), and blood lactate (Lac) with the severity of renal function damage and prognosis in patients with septic shock. Methods: Conducted from February 2022 to February 2024, this study included 116 septic shock patients treated at the First Affiliated Hospital of Anhui Medical University. Patients were divided into groups based on whether they developed acute kidney injury: 40 patients were included in the acute kidney injury group, and the remaining 76 were placed in the non-kidney injury group. The levels of HCT-ALB, SmtO2, CRT, and Lac were compared between the groups. Patients were followed up to assess their 28-day survival outcomes; 75 surviving patients were placed in the survival group, and 41 deceased patients in the death group. Differences in clinical data and levels of HCT-ALB, SmtO2, CRT, and Lac between the two groups were analyzed to explore the relationship of these indicators with patient prognosis. Results: Levels of HCT-ALB, CRT, and Lac were higher, while SmtO2 was lower in the acute kidney injury group compared to the non-kidney injury group (P&lt;0.05). Similarly, the death group exhibited higher levels of HCT-ALB, CRT, and Lac and lower SmtO2 levels compared to the survival group (P&lt;0.05). Univariate and multivariate analyses revealed that HCT-ALB, SmtO2, CRT, and Lac significantly impact patient survival outcomes, demonstrating high predictive value for patient mortality with respective AUC values of 0.834, 0.782, 0.903, and 0.918. The combined application of these indicators for predicting patient mortality had an AUC value of 0.985, which is higher than when the indicators were used individually. Conclusion: HCT-ALB, SmtO2, CRT, and Lac are significantly elevated in patients with acute kidney injury and deceased patients, closely correlating with the severity and prognosis of septic shock. These indicators can serve as important biomarkers for assessing the condition and prognosis of these patients.

LCP1 correlates with immune infiltration: a prognostic marker for triple-negative breast cancer

ObjectiveTriple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC.MethodsWe explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools.ResultsThe results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy.ConclusionLCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.

Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients.

Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI's The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients.