Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer

BACKGROUND: MicroRNAs (miRs) are frequently altered in colorectal cancer (CRC) and can be used as prognostic factors. OBJECTIVE: To confirm in stage III CRC patients a reported miR signature that was associated to the presence of metastatic disease. To correlate miR expression with microsatellite instability (MSI) and mutations in RAS and BRAF. METHODS: miR-21, miR-135a, miR-206, miR-335 and miR-Let-7a expression was analyzed by RT-qPCR in 150 patients out of the 329 patients used to analyze MSI and RAS and BRAF mutations. Association with disease free survival (DFS) and overall survival (OS) was analyzed. Data was confirmed by a multivariate analysis. RESULTS: MiR-21 high expression (p= 0.034) and miR-335 low expression (p= 0.0061) were significantly associated with MSI-H. A positive trend (p= 0.0624) between miR-135a high expression and RAS mutations was found. Lower miR-21 expression levels are associated with DFS (HR = 2.654, 95% CI: 1.066–6.605, p= 0.036) and a trend with OS (HR = 2.419, 95% CI: 0.749–7.815, p= 0.140). MiR-21 high expression significantly improves DFS of the poor prognosis group (T4 or N2) (p= 0.03). CONCLUSIONS: Association of increased expression of miR-21 and better prognosis in the poor prognostic group may be of interest and could be explored in future prospective clinical trials.

Survival stratification for colorectal cancer via multi-omics integration using an autoencoder-based model

Prognosis stratification in colorectal cancer helps to address cancer heterogeneity and contributes to the improvement of tailored treatments for colorectal cancer patients. In this study, an autoencoder-based model was implemented to predict the prognosis of colorectal cancer via the integration of multi-omics data. DNA methylation, RNA-seq, and miRNA-seq data from The Cancer Genome Atlas (TCGA) database were integrated as input for the autoencoder, and 175 transformed features were produced. The survival-related features were used to cluster the samples using k-means clustering. The autoencoder-based strategy was compared to the principal component analysis (PCA)-, t-distributed random neighbor embedded (t-SNE)-, non-negative matrix factorization (NMF)-, or individual Cox proportional hazards (Cox-PH)-based strategies. Using the 175 transformed features, tumor samples were clustered into two groups (G1 and G2) with significantly different survival rates. The autoencoder-based strategy performed better at identifying survival-related features than the other transformation strategies. Further, the two survival groups were robustly validated using “hold-out” validation and five validation cohorts. Gene expression profiles, miRNA profiles, DNA methylation, and signaling pathway profiles varied from the poor prognosis group (G2) to the good prognosis group (G1). miRNA–mRNA networks were constructed using six differentially expressed miRNAs (let-7c, mir-34c, mir-133b, let-7e, mir-144, and mir-106a) and 19 predicted target genes. The autoencoder-based computational framework could distinguish good prognosis samples from bad prognosis samples and facilitate a better understanding of the molecular biology of colorectal cancer.

Analysis of the Risk Factors in Prognosis of Kawasaki Disease With Coronary Artery Lesions

Kawasaki disease (KD) is one of the most common forms of systemic vasculitis in children. Pathological features include extensive inflammation of small and medium blood vessels throughout the body. The primary complication of KD is coronary artery lesions (CALs). A total of 640 children with KD were admitted to the Department of Pediatric Cardiology at Shengjing Hospital of China Medical University from January 2017 to December 2019. These patients comprised 52 coronary artery aneurysm (CAA) cases and 47 coronary artery dilation (CAD) cases. Echocardiography was performed during the acute KD phase and then at 1, 3, 6, 12, and 24 months after KD onset. Patients were divided into a poor prognosis group (n = 30) and a normal group (n = 69) based on CALs prognosis. Differences in laboratory data, clinical manifestations and coronary artery damage rates were compared between the two groups. Univariate analysis was performed on these data, and an ROC curve was used to analyze the efficacy of each risk factor. Univariate analysis revealed that age (months), number of coronary arteries involved (NACI), IgM, IgA and brain natriuretic peptide (ProBNP) levels were higher in the poor prognosis group compared with the normal group, procalcitonin (PCT) levels in the poor prognosis group were lower than in the normal group (P < 0.05).Conclusion: Age ≥ 18 months, IgM ≥ 1.07g/L, IgA ≥ 0.728g/L and NCAI ≥ 3 were poor prognostic factors of KD children with CALs. These parameters can be used as a reference indicator of early prediction where combined detection might improve the accuracy and sensitivity of prediction. Follow-up should be maintained to monitor changes in the coronary artery by echocardiography.

Clinical Features and Prognostic Factors of Acute Ischemic Stroke Related to Malignant Gastrointestinal Tumor

Objectives: To analyze the clinical and imaging features of acute ischemic stroke (AIS) related to gastrointestinal malignant tumor, and to explore the prognostic factors.Methods: Clinical data of consecutive patients with gastrointestinal malignant tumor complicated with AIS admitted to the Department of Neurology and Oncology in Lanzhou University Second Hospital from April 2015 to April 2019 were retrospectively analyzed. Patients were divided into good prognosis (mRS 0–2) and poor prognosis (mRS > 2) based on a 90-day mRS score after discharge. The multivariate logistic regression model was used to analyze the prognostic factors.Results: A total of 68 patients were enrolled with an average age of 61.78 ± 6.65 years, including 49 men (72.06%). There were 18 patients in the good prognosis group and 50 patients in the poor prognosis group. The univariate analysis showed that Hcy, D-dimer, thrombin–antithrombin complex (TAT), and three territory sign in magnetic resonance imaging (MRI) were the risk factors for poor prognosis. Multivariate analysis showed that increased D-dimer (OR 4.497, 95% CI 1.014–19.938) and TAT levels (OR 4.294, 95% CI 1.654–11.149) were independent risk factors for the prognosis in such patients.Conclusion: Image of patients with gastrointestinal malignant tumor-related AIS is characterized by three territory sign (multiple lesions in different vascular supply areas). Increased TAT and D-dimer levels are independent prognostic risk factors. TAT is more sensitive to predict prognosis than D-dimer.

Combination of NCCN Risk Stratification System and Pre-Transplant Minimal Residual Disease Levels for the Prognosis of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Background Numerous studies have confirmed that National Comprehensive Cancer Network (NCCN) risk stratification or pre-transplant minimal residual disease (MRD) levels can predict the risk of recurrence and survival after transplantation. But it is unclear whether combining these two parameters can more accurately predict prognosis. Methods We retrospectively analyzed 85 patients with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and constructed a new risk stratification tool combining NCCN risk stratification and pre-MRD levels. All patients were grouped by NCCN risk stratification (favorable/intermediate prognosis and poor prognosis group), pre-MRD levels (MRD (-) group (<0.1%) and MRD (+) group (≥0.1%)) and a combination of the above (low, intermediate and high risk groups), and graft-versus-host disease (GVHD) and prognosis were compared between groups. Results Relative to the favorable/intermediate prognosis group, OS and RFS were poorer in the poor prognosis group (71% vs 82%, P= .156; 60% vs 74%, P= .101) and CIR (29% vs 20%, P= .229) and NRM (23% vs 14%, P= .200) were better. The incidence of aGVHD and cGVHD was slightly lower in the favorable/intermediate prognosis group than in the poor prognosis group (38% vs 46%, P= .415; 10% vs 11%, P=. 572). Relative to the MRD (+) group, the MRD (-) group had significantly better OS and RFS (89% vs 59%, P= .002; 79% vs 50%, P= .003), lower CIR and NRM (15.1% vs 37.5%, P= .011; 11.3% vs 28%, P= .040), and a lower incidence of cGVHD (6% vs 19%, P= .022). The new risk stratification tool stratified patients into low, intermediate and high risk groups. Patients in the high-risk group had the highest incidence of aGVHD and cGVHD (42% vs 35% vs 53%, P= .606; 6% vs 11% vs 20%, P= .157). The difference in cGVHD between the low- and high-risk groups was significant (P= .038). Three-year OS was 93.9%, 70% and 60% (P= .011) and RFS was 85%, 62% and 46.7% (P= .009) for low-, intermediate- and high-risk patients, respectively. The differences in OS and RFS between the low- and intermediate-risk groups were statistically significant (P= .010; P= .025), as were the differences in OS and RFS between the low- and high-risk groups (P= .001; P= .001). Patients in the high-risk group had the highest CIR and NRM relative to those in the low- and intermediate-risk groups (9% vs 32% vs 33.3%, P= .027; 6% vs 24.3% vs 26.7%; P= .059). The differences in CIR (P= .012) and NRM (P= .028) were statistically significant in both the low-risk and intermediate-risk groups, as well as in the low- and high-risk groups (CIR: P= .028; NRM: P= .021). Multivariate analysis indicated that time to ANC recovery, time from diagnosis to transplantation, and novel risk stratification were independent prognostic factors. Conclusions Both pre-MRD levels and NCCN risk stratification predict AML prognosis after allo-HSCT, and combining the two can more accurately predict post-transplant prognosis. Disclosures No relevant conflicts of interest to declare.

Selection and Validation of Chemotherapy Beneficiaries among Elderly Nasopharyngeal Carcinoma (NPC) Patients Treated with Intensity-Modulated Radiation Therapy (IMRT): A Large Real-World Study

Purpose: Using real-world evidence, this study aimed to identify elderly nasopharyngeal carcinoma (NPC) patients who would benefit from chemotherapy.Methods and Materials: 1,714 elderly NPC patients between April 2007 and December 2017 were identified. Recursive partitioning analysis (RPA) was used to generate risk-stratified outcomes. Prognostic factors were performed for individual comparisons of different risk groups to assess chemotherapy benefits.Results: The median follow-up was 59.3 (0.39-170.09) months. Epstein Barr virus (EBV) DNA and T stage were included in the RPA-generated risk stratification, categorizing patients into a good-prognosis group (EBV DNA ≤ 4,000 copies/mL & T1-2), and a poor-prognosis group (EBV DNA ≤ 4,000 copies/mL & T3-4 and EBV DNA > 4,000 copies/mL & any T). Over survival (OS) was significantly higher in the good-prognosis group compared with the training set (HR = 0.309, 95% CI = 0.184-0.517; P < 0.001), and validated in the testing set (HR = 0.276, 95% CI = 0.113-0.670; P = 0.002). In the poor-prognosis group, a significantly improved OS for chemoradiotherapy (CRT) compared with RT alone was observed (HR = 0.70, 95% CI = 0.55-0.88; P = 0.003). Patients who received induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) and CCRT had a significantly improved OS compared with RT alone (IC+CCRT vs. RT alone: P = 0.002; CCRT vs. RT alone: P = 0.008) but not in the IC+RT group (P = 0.306). The 5-year OS for CRT vs. RT-alone with ACE-27 scores of 0, 1 and 2 were 76.0% vs. 70.0% (P = 0.014), 80.5% vs. 68.2% (P = 0.150) and 58.5% vs. 62.2% (P = 0.490), respectively; for those aged 60-64, 65-70 and ≥70 years old they were 80.9% vs. 75.9% (P = 0.068), 73.3% vs. 63.4% (P = 0.270) and 64.8% vs. 67.1% (P = 0.820), respectively.Conclusions: For elderly NPC patients a simple screening cutoff for chemotherapy beneficiaries might be EBV DNA＜4000 copies/ml & T3-4 and EBV DNA ≥4000 copies/ml & any T, but not for those >70 years old and with an ACE-27 score > 1. IC+CCRT and CCRT were effective forms of chemotherapy.

Study on the Correlation Factors of Tumour Prognosis after Intravascular Interventional Therapy

Noninvasive or minimally invasive interventional surgery was selected, and the complications were less and had no significant impact on the quality of life of patients. Tumour patients are often accompanied by cerebrovascular diseases, metabolic diseases, and other basic diseases, which more or less adversely affect the surgical efficacy of tumour. In this paper, endovascular remobilization was used to treat tumour; the basic condition of patients before operation and the interventional operation plan were introduced. Through the analysis of clinical data and prognosis evaluation results of tumour patients receiving intravascular interventional therapy, the patients were divided into good prognosis group and poor prognosis group according to the modified Rankin scale score at discharge. The relationship between gender, age, history of hypertension, tumour width, tumour size, preoperative Hunt-Hess grade, interventional surgery method, and prognosis related to intravascular interventional therapy was explored. The results showed that intravascular interventional therapy for tumour patients can obtain a good prognosis, which provides a reference for the future preoperative assessment of treatment risk and possible prognosis and provides a theoretical basis for the formulation of treatment plan to improve prognosis.

Predictive Value of MPV and Plasma NT-ProBNP Combined with the Simplified Geneva Scale for the Prognosis of Acute Pulmonary Embolism

Objective. To explore the predictive value of mean platelet volume (MPV) and plasma N-terminal probrain natriuretic peptide (NT-ProBNP) combined with a simplified Geneva scale for the prognosis of acute pulmonary embolism (APE). Methods. The clinical data of 68 patients with APE admitted to our hospital from October 2017 to October 2019 were collected. According to the prognosis, the patients were divided into a good prognosis group (n = 45) and a poor prognosis group (n = 23). The clinical data, laboratory clinical indexes, and simplified Geneva scale scores were recorded for the two groups. The risk factors of poor prognosis were analyzed by binary multivariate logistic regression analysis; the predictive ability of each index on the prognosis of patients with APE was analyzed by the ROC curve. Results. The incidences of deep vein thrombosis, diabetes, and hyperlipidemia in the poor prognosis group were higher than those in the good prognosis group ( P < 0.05 ). PLT, platelet distribution width (PDW), MPV, and plasma NT-ProBNP in the poor prognosis group were higher than those in the good prognosis group ( P < 0.05 ). The simplified Geneva scale score of the poor prognosis group was higher than that of the good prognosis group ( P < 0.05 ). PDW, MPV, plasma NT-ProBNP, and simplified Geneva scale were all independent risk factors for the poor prognosis of APE patients ( P < 0.05 ). The AUC of MPV in predicting the prognosis of APE patients was 0.818 (95% CI: 0.712–0.925). When the optimal cutoff value was 0.571, the sensitivity was 77.1%, and the specificity was 80.0%. The AUC of plasma NT-ProBNP in predicting the prognosis of APE patients was 0.762 (95% CI: 0.634–0.891). When the optimal cutoff value was 0.475, the sensitivity was 71.5%, and the specificity was 76.0%. The AUC of the simplified Geneva scale in predicting the prognosis of APE patients was 0.749 (95% CI: 0.618–0.879). When the optimal cutoff value was 0.469, the sensitivity was 82.9%, and the specificity was 64.0%. The AUC of MPV and plasma NT-ProBNP combined with the simplified Geneva scale in predicting the prognosis of APE patients was 0.907 (95% CI: 0.826–0.988). When the optimal cutoff value was 0.726, the sensitivity was 88.6%, and the specificity was 84.0%. Conclusion. MPV, plasma NT-ProBNP, and simplified Geneva scale have a certain predictive value for the prognosis of APE. Compared with a single index, the combination of the three indexes has a significant improvement in predicting the prognosis of APE and has better clinical value.

The value of arterial spin labeling imaging in the classification and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy

Objective: This study aims to investigate the correlation between cerebral blood flow (CBF) values and neonatal behavioral neurological assessment (NBNA) in hypoxic-ischemic encephalopathy (HIE), the relationship between early CBF value changes and the prognosis of neonatal HIE, and the consistency between the clinical grading and magnetic resonance (MR) grading of HIE. Methods: Forty neonates with HIE were scanned using the three-dimensional arterial spin labeling (ASL) sequencing of the cranial magnetic resonance imaging (MRI). These newborns were classified as having mild, moderate and severe HIE, according to the clinical grading, and as being normal or having mild, moderate, or severe HIE, according to the MRI grading. Then, the consistency of these two grading systems were compared. Afterwards, the differences in the CBF values of neonates in groups with mild, moderate and severe HIE were compared. In addition, these neonates were grouped according to their NBNA scores. A score of ≥35 was considered a good prognosis, while a score of ≤35 was considered a poor prognosis. The differences in CBF values between these two groups were compared, and the correlation between the CBF values and NBNA scores was determined. Results: There was a strong consistency between the evaluation results for the clinical grading and MR grading (kappa value = 0.672, P<0.001). The differences in CBF values for the basal ganglia (BG) area and thalamus, and the differences in NBNA scores for groups with mild, moderate, or severe HIE were statistically significant (P<0.05). The differences between the poor prognosis group and good prognosis group, in terms of the CBF values for the BG area and thalamus, and the NBNA scores, were statistically significant (P<0.05). The CBF values in the BG region and thalamus were closely and negatively correlated with the NBNA scores. Conclusion: Early CBF values in the BG area and thalamus can objectively and visually reflect the severity of the HIE, and be used to predict the outcome of functional brain damage, allowing early neuroprotective treatment to be initiated. The higher the perfusion in the BG region and thalamus, the lower the NBNA score, and the worse the prognosis would likely be. ASL combined with the NBNA score provides a more comprehensive classification for HIE and a more accurate assessment of the clinical prognosis, providing more medical imaging information for early clinical treatment.

Therapeutic Effects of Microsurgical Clipping at Different Time Points on Intracranial Aneurysm and Prognostic Factors

Background Microsurgical clipping is effective for treating early rupture hemorrhage in intracranial aneurysm (IA) patients. We aimed to evaluate the therapeutic effects of microsurgical clipping at different time points on IA and to explore prognostic factors. Methods A total of 102 eligible patients were divided into good prognosis group (n = 87) and poor prognosis group (n = 15) according to Glasgow Outcome Scale (GOS) scores at discharge. The effects of microsurgical clipping at different time points (within 24 h, 48 h and 72 h) were compared. The incidence rates of postoperative complications in patients with different Hunt–Hess grades were compared. Prognostic factors were determined by multivariate logistic regression analysis. The nomogram prediction model was established based on independent risk factors and validated. Results The good recovery and success rates of complete aneurysm clipping were significantly higher in patients undergoing surgery within 24 h after rupture. The incidence rate of complications was significantly higher in patients with Hunt–Hess grade IV. Good and poor prognosis groups had significantly different age, history of hypertension, preoperative intracranial hematoma volume, aneurysm size, preoperative Hunt–Hess grade, later surgery, postoperative complications and National Institute of Health Stroke Scale (NIHSS) score, as independent risk factors for prognosis. The nomogram model predicted that poor prognosis rate was 14.71%. Conclusion Timing (within 24 h after rupture) microsurgical clipping benefits the prognosis of IA patients. Age, history of hypertension, preoperative intracranial hematoma volume, aneurysm size, preoperative Hunt–Hess grade, later surgery, postoperative complications and NIHSS score are independent risk factors for poor prognosis.