Prognosis Of Patients Research Articles

Gut Microbiome and colorectal cancer: discovery of bacterial changes with metagenomics application in Turkısh population.

Colorectal cancer (CRC) is the 3rd most common cancer in the world and colonic carcinogenesis is a multifactorial disease that involves environmental and genetic factors. Gut microbiota plays a critical role in the regulation of intestinal homeostasis. Increasing evidence shows that the gut microbiome plays a role in CRC development and may be a biomarker for early diagnosis. This study aimed to determine the clinical prognostic significance of gut microbiota in CRC patients in the Turkish population by metagenomic analysis and to determine the microbial composition in tumor tissue biopsy samples. Tissue biopsies were taken from the participants with sterile forceps during colonoscopy and stored at -80°C. Then, DNA isolation was performed from the tissue samples and the V3-V4 region of the 16S rRNA gene was sequenced on the Illumina MiSeq platform. Quality control of the obtained sequence data was performed. Operational taxonomic units (OTUs) were classified according to the Greengenes database. Alpha diversity (Shannon index) and beta diversity (Bray-Curtis distance) analyses were performed. The most common bacterial species in CRC patients and healthy controls were determined and whether there were statistically significant differences between the groups was tested. A total of 40 individuals, 13 CRC patients and 20 healthy control individuals were included in our metagenomic study. The mean age of the patients was 64.83 and BMI was 25.85. In CRC patients, the level of Bacteroidetes at the phylum taxonomy was significantly increased (p = 0.04), the level of Clostridia at the class taxonomy was increased (p = 0.23), and the level of Enterococcus at the genus taxonomy was significantly increased (p = 0.01). When CRC patients were compared with the control group, significant increases were detected in the species of Gemmiger formicilis (p = 0.15), Prevotella copri (p = 0.02) and Ruminococcus bromii (p = 0.001) at the species taxonomy. Metagenomic analysis of intestinal microbiota composition in CRC patients provides important data for determining the treatment options for these patients. The results of this study suggest that it may be beneficial in terms of early diagnosis, poor prognosis and survival rates in CRC patients. In addition, this metagenomic study is the first study on the colon microbiome associated with CRC mucosa in the Turkish population.

Silencing DOCK2 Attenuates Cardiac Fibrosis Following Myocardial Infarction in Mice Via Targeting PI3K/Akt and Wnt/β-Catenin Pathways.

Cardiac fibrosis following myocardial infarction (MI) seriously affects the prognosis and survival rate of patients. This study aimed to determine the effect and regulation mechanism of the dedicator of cytokinesis 2 (DOCK2) during this process. Experiments were carried out in mice in vivo, and in Ang II treated cardiac fibroblasts (CFs) in vitro. DOCK2 was increased in mouse myocardial tissues after MI and Ang II-treated CFs. In MI mice, DOCK2 silencing improved cardiac function, and ameliorated cardiac fibrosis. DOCK2 knockdown suppressed the activation of CFs and decreased the expression of α-SMA, collagen I, and collagen III. Suppression of DOCK2 mitigated Ang II induced migration of CFs. DOCK2 inhibition reduced the activity of the PI3K/Akt and Wnt/β-catenin pathways, while this change could be reversed by the pathway activators, SC79 and SKL2001. In summary, DOCK2 suppression improves cardiac dysfunction and attenuates cardiac fibrosis after MI via attenuating PI3K/Akt and Wnt/β-catenin pathways.

Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report

BackgroundSurgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer.Case presentationWe report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings.ConclusionA total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

FGFR2 fusion/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma.

Increasing evidence highlights that fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement shows important therapeutic value for patients with intrahepatic cholangiocarcinoma (ICC). This study aims to explore the association of FGFR2 status with the prognosis and immune cell infiltration profiles of patients with ICC. A total of 226 ICC tissue samples from patients who received surgery at the Department of Liver Surgery at Zhongshan Hospital, Fudan University, were collected retrospectively and assigned to a primary cohort (n = 152) and validation cohort (n = 74) group. Fluorescence in situ hybridization was performed to determine FGFR2 status. Multiplex immunofluorescence (mIF) staining and immunohistochemistry were performed to identify immune cells. Thirty-two (14.2%) ICC tissues presented with FGFR2 fusion/rearrangement. FGFR2 fusion/rearrangement was associated with low levels of carcinoembryonic antigen (CEA, P = .026) and gamma glutamyl transferase (γ-GGT, P = .003), low TNM (P = .012), CNLC (P = .008) staging as well as low tumor cell differentiation (P = .016). Multivariate COX regression analyses revealed that FGFR2 fusion/rearrangement was an independent protective factor for both overall survival (OS) and relapse-free survival in patients with ICC. Furthermore, correlation analysis revealed that an FGFR2 fusion/rearrangement was associated with low levels of Tregs and N2 neutrophils and high levels of N1 neutrophils infiltrating into tumors but not with CD8+ T-cell or macrophage tumor infiltration. FGFR2 fusion/rearrangement may exert a profound impact on the prognosis of ICC patients and reprogram the tumor microenvironment to be an immune-activated state. FGFR2 status may be used for ICC prognostic stratification and as an immunotherapeutic target in patients with ICC.

Risk factors of prognosis for spontaneous cerebellar hemorrhage: a systematic review and meta-analysis

BackgroundThe most deadly type of spontaneous intracerebral hemorrhage is spontaneous cerebellar hemorrhage (SCH). The purpose of this meta-analysis was to investigate risk factors for prognosis in SCH patients to provide a basis for taking preventive and therapeutic measures.MethodsSeven electronic databases were searched from inception to May 2023 for randomized controlled trial, cohort study, case control study and cross-sectional study on prognosis of spontaneous cerebellar hemorrhage. The quality of the selected studies were assessed by the American Agency for Healthcare Research and Quality (AHRQ). To assess the impact of the included risk factors on the prognosis of spontaneous cerebellar hemorrhage, combined odds ratios (ORs) with matching 95% confidence intervals (CIs) were combined.ResultsEight studies were included, including 539 participants. And a total of 31 potentially associated risk factors were identified. Ultimately, 6 risk factors were included in the meta-analysis after assessing. The factors supported by moderate evidence include the hydrocephalus (OR = 4.3, 95% CI: 2.33 to 7.91) and drug-induced coagulopathy (OR = 2.74, 95% CI: 1.23 to 6.09). The factors supported by limited evidence include the intraventricular bleeding(OR = 1.86, 95% CI: 1.13 to 3.07) and hematoma size>3 cm(OR = 3.18, 95% CI: 1.87 to 5.39). Meta-analysis revealed no association between hypertension, diabetes mellitus and SCH prognosis.ConclusionThe current meta-analysis revealed obvious risk factors for prognosis in spontaneous cerebellar hemorrhage patients, including hydrocephalus, drug-induced coagulopathy, intraventricular bleeding and hematoma size>3 cm.

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.

Lymphocyte-to-C-reactive protein ratio and score in patients with heart failure: Nutritional status, physical function, and prognosis.

In heart failure (HF), inflammation is linked to malnutrition and impaired physical function. In this study, we aimed to assess how novel nutritional-inflammatory markers and lymphocyte-to-C-reactive protein ratio (LCR) and score (LCS) are associated with the nutritional status, physical function, and prognosis of patients with HF. This study was a secondary analysis of the FRAGILE-HF study, a prospective observational study conducted across 15 hospitals in Japan. We included 1212 patients (mean age, 80.2±7.8years; 513 women) hospitalized with HF, who were classified into three groups according to their LCS score: 0 (n=498), 1 (n=533), and 2 (n=181). Baseline data on physical examination, echocardiography, blood test results (including lymphocyte counts and CRP levels), and oral medication usage were collected in a clinically compensated state before discharge. Nutritional status and physical function were evaluated using several indices and tests. The primary outcome of this study was all-cause death within 2years. Univariate and multivariate linear regression analyses were performed to evaluate the associations among the nutritional status, physical function, and LCR/LCS. Patients with an LCS score of 2 were older and had a lower body mass index than those in the other two groups. Multivariate linear regression analysis revealed that lower LCR and higher LCS were independently associated with worse nutritional status, lower handgrip strength, shorter physical performance battery score, and shorter 6-min walk distance. At 2years, all-cause death occurred in 254 patients: 86 (17.6%), 113 (21.5%), and 55 (30.9%) with LCS scores of 0, 1, and 2, respectively (P=0.001). Cox proportional hazards analysis revealed that LCR and LCS were significantly associated with 2-year mortality even after adjusting for the conventional risk model (LCS score, 0 vs. 2: hazard ratio, 1.64; 95% confidence interval [CI]; 1.14-2.35; P=0.007; log-transformed LCR: hazard ratio, 0.88; 95% CI, 0.81-0.95; P=0.002). LCR yielded additional prognostic predictability compared with the conventional risk model (continuous net reclassification improvement, 0.153; 95% CI, 0.007-0.299; P=0.041). LCR and LCS emerge as potential predictors of nutritional status, physical function, and prognosis in older patients with HF.

Rationale and Design of a Multicenter Trial on Exploratory Analysis of the Effects of Advance Care Planning Guided by the Prediction Program of Heart Failure Prognosis on Quality of Life in Patients With Heart Failure - ACQUAINT-Trial.

Background: Preplanning of care is necessary for patients with endstage heart failure (HF), but advance care planning (ACP) before the loss of a patient's comprehensive capacity is not yet routine for the public or the medical community. The challenge in accurately predicting a patient's prognosis is a strong barrier to implementing ACP. To address this problem, several models for risk stratification have been proposed and are available in clinical settings. Methods and Results: We randomized the procedure to provide estimated patient survival information to attending physicians and then assessed whether there was a change in (1) the frequency of ACP initiation occurred (physician-side evaluation), and/or (2) the patients' quality of life, including mental state (patient-side evaluation). Conclusions: This multicenter, open-label, single-blinded randomized clinical trial aims to assess the hypothesis that providing information on the estimated survival of a patient to the attending physicians will improve the frequency of ACP initiation and quality of life in patients with HF.

Conditional survival and the prognostic value of serum carcinoembryonic antigen level in oldest old with colorectal cancer

BackgroundTo evaluate the clinical value of serum CEA levels and their implications on the diagnostic value of the conventional TNM staging system in the oldest-old patients with colorectal cancer (CRC).MethodsThe recruited subjects were colorectal cancer patients aged 85 and older. The cutoff value for normal CEA level is 5 ng/mL. Patients with elevated CEA levels were categorized as stage C1, and those with normal CEA levels as stage C0. A number of Cox proportional hazard regression models were established to evaluate the prognosis of different prognostic factors with hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier method was utilized to display the disparate prognostic impact of multiple clinicopathological factors with the log-rank test.ResultsA total of 17,359 oldest-old patients diagnosed with CRC were recruited from the SEER database. The conditional survival of oldest-old patients with CRC was dismal with a 1-year conditional survival of only 11%, 18%, and 30% for patients surviving 1, 3, and 5 years, respectively. Patients with stage C1 exhibited a 48.5% increased risk of CRC-specific mortality compared with stage C0 (HR = 1.485, 95%CI = 1.393–1.583, using stage C0 patients as the reference, P < 0.001). All the stage C0 patients indicated lower HRs relative to the corresponding stage C1 patients.ConclusionsDismal conditional survival of oldest-old patients with CRC should be given additional consideration. C stage influences the prognosis of oldest-old patients with CRC.

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.

Oncogenic Gene CNOT7 Promotes Progression and Induces Poor Prognosis of Glioma.

Glioma is the most common malignant brain tumor in the central nervous system with the poor prognosis of patients. The CNOT7 (CCR4-NOT Transcription Complex Subunit 7) is an important functional subunit of CCR4-NOT protein complex that has not been reported in glioma. In this study, we aimed to explore the function of CNOT7 in glioma. The TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) databases were used for investigating the expression and survival condition of CNOT7 in glioma. The cellular function experiments of qRT-PCR, CCK-8 assays, wound healing assays, and Transwell assays were conducted to verify the function of knockdown CNOT7 in the glioma cell lines DBTRG and U251. Enrichment analysis was used to explore the molecular mechanism of CONT7 in glioma. What is more, the upstream regulation transcription factors of CNOT7 were analyzed based on the ChIP-Atlas and cBioportal (provisional) databases, and verified by the qRT-PCR and luciferase reporter assay. The CNOT7 was highly expressed in glioma and presented the poorer prognosis. The knockdown of CNOT7 inhibited the proliferation, migration, and invasion of glioma cell line, compared to control group. The enrichment analysis revealed that the CNOT7 participated in the development of glioma via G2M checkpoint, E2F targets, IL6-JAK-STAT3, and TNF-α signaling pathways via NF-κB. Besides, it was found that the HDAC2 (Human histone deacetylase-2) contributes to increased CNOT7 expression in glioma. The high-expressed CNOT7 is an oncogene with poor prognosis and participate the progression of glioma.

Study on the Prediction of Liver Injury in Acute Pancreatitis Patients by Radiomic Model Based on Contrast-Enhanced Computed Tomography.

to predict liver injury in acute pancreatitis (AP) patients by establishing a radiomics model based on contrast-enhanced computed tomography (CECT). a total of 1223 radiomic features were extracted from late arterial-phase pancreatic CECT images of 209 AP patients (146 in the training cohort and 63 in the test cohort), and the optimal radiomic features retained after dimensionality reduction by least absolute shrinkage and selection operator (LASSO) were used to construct a radiomic model through logistic regression analysis. In addition, clinical features were collected to develop a clinical model, and a joint model was established by combining the best radiomic features and clinical features to evaluate the practicality and application value of the radiomic models, clinical model and combined model. four potential features were selected from the pancreatic parenchyma to construct the radiomic model, and the area under the receiver operating characteristic curve (AUC) of the radiomic model was significantly greater than that of the clinical model for both the training cohort (0.993 vs. 0.653, p = 0.000) and test cohort (0.910 vs. 0.574, p = 0.000). The joint model had a greater AUC than the radiomics model for both the training cohort (0.997 vs. 0.993, p = 0.357) and test cohort (0.925 vs. 0.910, p = 0.302). the radiomic model based on CECT has good performance in predicting liver injury in AP patients and can guide clinical decision-making and improve the prognosis of patients with AP.</p>.

Comparative analysis of different treatment strategies for septic spondylitis: a retrospective study of one hundred and twelve patients.

To compare the clinical efficacy and prognosis differences between conservative treatment and surgical treatment in patients with non-serious neurologically intact pyogenic spondylitis (Nsi-Nsni-PS), and to provide theoretical reference for the clinical treatment of Nsi-Nsni-PS patients. A retrospective analysis was conducted on 112 cases of Nsi-Nsni-PS patients treated in our hospital from June 2016 to June 2021. According to different treatment methods, they were divided into conservative treatment group (53 cases) and surgical treatment group (59 cases). The general data, laboratory tests, imaging examinations, length of hospital stay, duration of antibiotic use, VAS for pain before and after treatment, ODI, local kyphotic angle correction of diseased vertebrae, and recurrence rate were collected and analyzed in both groups. SPSS 26.0 statistical software was used for analysis. Measurement data were expressed as mean ± standard deviation, and independent sample t-test or rank sum test was used for comparison between groups, while variance analysis was used for intra-group comparison. Count data were expressed as number (%) and compared between groups using chi-square test or Fisher's exact test. Mann-Whitney U test was used to evaluate the changes in local kyphotic angle between the two groups. A p value < 0.05 was considered statistically significant. There were no significant differences in general data and imaging characteristics between the two groups (P > 0.05); there were no statistically significant differences in the positive culture rate of pathogens, length of hospital stay, duration of antibiotic use, treatment complications, WBC, CRP, ESR levels at admission and discharge, VAS and ODI at admission and last follow-up between the two groups (P > 0.05). The WBC and CRP levels of patients in the conservative group at discharge were lower than those in the surgical group (P < 0.05), and there was no significant difference in the decrease in inflammatory indicators (WBC, CRP, ESR) between the two groups (P > 0.05). By the last follow-up, the neurological function of patients in both groups had significantly improved compared to admission (P < 0.05), with 12 out of 15 ASIA grade D patients in the conservative group recovering to grade E, and 21 out of 25 grade D patients in the surgical group recovering to grade E, with no worsening of neurological function in either group. The differences in VAS and ODI scores at the last follow-up compared to before treatment were statistically significant in both groups (P < 0.05), and all patients regained normal activity. Compared with before treatment, the correction degree of local kyphotic angle in the surgical group at the last follow-up was 0.93 ± 4.94°, slightly higher than that in the conservative group (-0.83 ± 3.37°), and the difference was statistically significant(P < 0.05). During our follow-up, we found that both conservative and surgical treatments achieved satisfactory clinical outcomes in patients with Nsi-Nsni-PS. Compared to conservative treatment, surgical intervention did not demonstrate significant advantages in reducing hospitalization time and antibiotic usage duration, increasing pathogen culture positivity rate, lowering treatment complications, or controlling recurrence. However, surgical intervention showed superiority in correcting the local kyphotic angle of spinal lesions, albeit with relatively increased surgical trauma, risks, and treatment costs. At the last follow-up, the surgical group did not exhibit better long-term efficacy. Therefore, when formulating clinical treatment strategies for patients with Nsi-Nsni-PS, it may be preferable to prioritize conservative treatment, supplemented by the use of sensitive or empiric antibiotics for infection management, to improve patient prognosis.

Response to chemotherapy could predict the prognosis of esophageal squamous cell carcinoma treated with neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by surgery: long-term results in a single institute.

Preoperative chemotherapy with 5-fluorouracil and cisplatin (FP) followed by surgery has been considered a standard treatment for patients with stage II/III esophageal squamous cell carcinoma (ESCC) based on the results of a phase III trial (JCOG9907) in Japan. Subsequently, the phase III NExT trial (JCOG1109) revealed the survival benefit of the neoadjuvant DCF regimen, which adds docetaxel to FP, and it became a standard treatment. However, the long-term results and prognostic factors of neoadjuvant DCF therapy in the real world are unknown. We retrospectively investigated 50 patients with ESCC treated with neoadjuvant DCF therapy from July 2012 to December 2017 at The University of Tokyo Hospital. Median overall survival (OS) and progression-free survival (PFS) were 32.3 [95% confidence interval (CI) 21.0-NA] and 10.0months (95% CI 6.3-15.6), respectively. Median OS [not reached (95% CI 31.5-NA) vs. 21.4months (95% CI 13.5-33.0); p = 0.028] and PFS [83.3months (95% CI 6.4-NA) vs. 7.4months (95% CI 6.0-12.8] were significantly longer in patients with an objective response than in non-responders. Of 44 surgical cases, median PFS tended to be longer in pathological lymph node metastasis-negative patients. Conversely, survival did not differ according to cStage (II/III vs. IV) or the average relative dose intensity (ARDI, ≥ 85% vs. < 85%). The response to neoadjuvant DCF therapy could predict patient prognosis. Additionally, pN+ tended to increase the recurrence risk, whereas cStage and ARDI did not influence survival.

Transforming Cancer Care: The Impact of AI-Driven Strategies.

AI is a critical component in healthcare, especially in the application of precision medicine where patients' characteristics, including genetic makeup, determine the treatment options that should be implemented. AI sorts big data, predicting people's reactions to specific treatments, the right combinations of drugs, and possible side effects, therefore increasing the efficiency of the treatment process and decreasing negative outcomes. This article briefly presents the ethical issues and concerns that might arise due to the integration of AI in society, such as the privacy of data, the issues of bias in the algorithms, and the issues of interpretability of the AI systems. Nevertheless, there is no doubt that AI can bring qualitative changes in cancer care based on its potential to enhance patient prognosis and reduce health care costs, as well as become a defining feature of the standard of care.

Myofibroblasts derived type V collagen promoting tissue mechanical stress and facilitating metastasis and therapy resistance of lung adenocarcinoma cells

Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.

Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer.

Tumor-associated macrophages(TAM),a major component of the tumor microenvironment, play key roles in tumor formation and progression; however, mechanisms underlying TAM-induced tumor progression are complex and not well known. We previously reported that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts. We examined ANGPTL2 expression in paraffin-embedded tumor samples from resected specimens of 221 patients with esophageal cancer. Patients were subdivided into four groups based on immunohistochemistry scores described above: ANGPTL2-low/TAM-low, ANGPTL2-low/TAM-high, ANGPTL2-high/TAM-low, and ANGPTL2-high/TAM-high groups. Gene expression datasets of esophageal cancer cell lines were obtained from the cancer cell line encyclopedia public database. In this study, we demonstrate that TAM infiltration is associated with poor prognosis in patients with esophageal cancer whose tumor cells show relatively higher ANGPTL2 expression levels; however, TAM infiltration did not affect prognosis in patients with ANGPTL2-low-expressing esophageal cancer, suggesting that ANGPTL2 expression in esophageal cancer cells is required for TAM-induced tumor progression. Our analysis of public datasets indicates a potential positive correlation of ANGPTL2 expression levels with that of transforming growth factor (TGF)-β, a TAM-activating factor, in esophageal cancer cell lines. We conclude that ANGPTL2 signaling in tumor cells supports TAM-induced tumor progression and contributes to poor prognosis in patients with esophageal cancer. These findings overall provide novel insight into pro-tumor ANGPTL2 functions and illustrate the essential role of cancer cell/TAM crosstalk in cancer progression.

Tumor purity-related genes for predicting the prognosis and drug sensitivity of DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics. Datasets from the Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factors that influenced the prognosis. Drug-sensitive prediction was performed to evaluate the value of the model. VCAN, CD3G, and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68 + macrophages and CD8 + T cells was associated with better prognosis. In addition, CD3G+T cells ratio was significantly correlated with CD68 + macrophages, CD4 + T cells, and CD8 +T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB, and CD3G work well in predicting the prognosis and drug sensitivity. VCAN, CD3G, and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients. This work is supported by the Shenzhen High-level Hospital Construction Fund and CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-062).

Tumor purity-related genes for predicting the prognosis and drug sensitivity of DLBCL patients

Background:Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics.Methods:Datasets from the Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factors that influenced the prognosis. Drug-sensitive prediction was performed to evaluate the value of the model.Results:VCAN, CD3G, and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68 + macrophages and CD8 + T cells was associated with better prognosis. In addition, CD3G+T cells ratio was significantly correlated with CD68 + macrophages, CD4 + T cells, and CD8 +T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB, and CD3G work well in predicting the prognosis and drug sensitivity.Conclusions:VCAN, CD3G, and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients.Funding:This work is supported by the Shenzhen High-level Hospital Construction Fund and CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&amp;T-B-062).

Inflammatory biomarkers may be associated with poor outcomes after mechanical thrombectomy

BackgroundMechanical thrombectomy (MT) has become the mainstay of treatment for acute ischemic stroke (AIS) recently. This case-control study aimed to identify the pivotal role of inflammation in the prognosis of AIS patients after MT.MethodsAltogether, 70 AIS patients who underwent MT were retrospectively recruited for this study. Receiver operating characteristic analysis was performed to demonstrate the sensitivity and specificity of the inflammatory variables for predicting prognosis. A meta-analysis was performed to pool the published results together. Stata software was used for analysis.ResultsThere was no differences in pre-MT inflammatory biomarkers between patients who survived and those who died, as well as patients with modified Rankin Scale (mRS) 0–2 and mRS ≥ 3. In contrast, post-MT C-reactive protein (CRP) levels might be a potential parameter to predict death after thrombectomy [area under the curve (AUC), 95%confidence interval (CI), 0.737, 0.587–0.887; p = 0.005; optimal cutoff value = 4.565]. Moreover, post-MT monocyte count might be an appropriate parameter to predict poor long-term prognosis after thrombectomy (AUC, 95%CI, 0.704, 0.575–0.833; p = 0.017; optimal cutoff value = 0.345). A meta-analysis revealed that the pre-MT inflammatory indices, including white blood cell count (weighted mean difference, 95%CI, 1.32, 1.01—1.63), neutrophil count (1.23, 0.95—1.51), monocyte count (0.05, 0.02—0.09), neuthrophil-to-lymphocyte ratio (2.42, 1.98—2.87) and platelet-to-lymphocyte ratio (24.65, 7.99—41.32), were higher in patients with 3-month mRS ≥ 3, and the lymphocyte count (−0.31,−0.43 to −0.18) was lower in this cohort.ConclusionsInflammatory indices were significantly associated with the prognosis of patients undergoing MT, especially post-MT CRP and monocyte count, which can predict long-term outcomes.