ObjectiveTo detect the expression of Krüppel like factor 8 (KLF8) in breast cancer tissues and cells and to explore the clinical significance of KLF8.Methods① The Oncomine database was used to analyze the differential expression of KLF8 mRNA in the breast cancer tissues. The Kaplan-Meier Plotter database was used to analyze the relationship between KLF8 mRNA expression and prognosis (relapse free survival, overall survival, post-progression survival, and distant metastasis-free survival) of patients with breast cancer. ② The quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the KLF8 expression levels in the 16 clinical patients with breast cancer and 7 breast cancer cell lines (MDA-MB-231, MCF-12A, Hs-578T, MCF-7, BT-474, MDA-MB-453, ZR-75-30) and normal breast epithelial cell lines MCF-10A, and the immunofluorescence was used to further detect the localization of KLF8 expression in the 2 breast cancer cell lines with higher KLF8 expression level. ③ The immunohistochemistry was used to detect the expression of KLF8 protein in 135 cases of breast cancer tissue microarrays, and the relationships between KLF8 protein expression and clinicopathologic characteristics or overall survival were analyzed.Results① The Oncomine database showed that KLF8 mRNA expression in the breast cancer tissues was higher than that in the normal breast tissues (P<0.001). The median KLF8 mRNA expression level was taken as the cut-off point for high or low KLF8 expression. The results of Kaplan-Meier Plotter data analysis showed that the prognosis (relapse free survival, overall survival, postprogression survival, and distant metastasis-free survival) of patients with low KLF8 mRNA expression were better than those of patients with high KLF8 mRNA expression (P<0.05). ② The results of qRT-PCR and Western blot all showed that the KLF8 mRNA and protein expression levels in the breast cancer tissues were higher than those in the adjacent normal tissues (P=0.002, P<0.001). In addition, the Western blot results showed that the expression of KLF8 protein in the 7 breast cancer cell lines was higher than that in the normal breast epithelial cell lines MCF-10A respectively, and KLF8 protein mainly expressed in the cytoplasm of breast cancer cells and highly expressed in the nuclear of a few cells. ③ There were 63 cases of high KLF8 expression and 72 cases of low KLF8 expression by the immunohistochemical analysis of 135 patients with breast cancer tissue microarray (the H-score of the immunohistochemical test results was 75 as the cut-off point, H-score >75 was the high KLF8 expression and H-score ≤75 was the low KLF8 expression), the differences of statuses of estrogen receptor (ER) and progesterone receptor (PR) between the patient with high KLF8 expression and low KLF8 expression were significant (P<0.05). The Kaplan-Meier survival curve analysis showed that the prognosis of patients with high KLF8 expression was worse than that of patients with low KLF8 expression (P=0.002). The univariate analysis showed that the TNM stage, statuses of ER and PR, and KLF8 expression were related to the prognosis of patients with breast cancer (P<0.05), further multivariate Cox proportional hazards regression analysis indicated that the later stage of TNM and high KLF8 expression were the independent risk factors (P<0.05).ConclusionsThe results of this study suggest that KLF8 highly expresses in both breast cancer tissues and breast cancer cells, which is related to the statuses of ER and PR and prognosis of patients with breast cancer. KLF8 might be involved in the progression of breast cancer as an oncogenic gene, or it might provide a new direction for prognosis judgment and molecular targeted therapy of breast cancer.
ObjectiveTo investigate the relation between disulfidptosis-related genes (DRGs) and prognosis or immunotherapy response of patients with pancreatic cancer (PC). MethodsThe transcriptome data, somatic mutation data, and corresponding clinical information of the patients with PC in The Cancer Genome Atlas (TCGA) were downloaded. The DRGs mutated in the PC were screened out from the 15 known DRGs. The DRGs subtypes were identified by consensus clustering algorithm, and then the relation between the identified DRGs subtypes and the prognosis of patients with PC, immune cell infiltration or functional enrichment pathway was analyzed. Further, a risk score was calculated according to the DRGs gene expression level, and the patients were categorized into high-risk and low-risk groups based on the mean value of the risk score. The risk score and overall survival of the patients with high-risk and low-risk were compared. Finally, the relation between the risk score and (or) tumor mutation burden (TMB) and the prognosis of patients with PC was assessed. ResultsThe transcriptome data and corresponding clinical information of the 177 patients with PC were downloaded from TCGA, including 161 patients with somatic mutation data. A total of 10 mutated DRGs were screened out. Two DRGs subtypes were identified, namely subtype A and subtype B. The overall survival of PC patients with subtype A was better than that of patients with subtype B (χ2=8.316, P=0.003). The abundance of immune cell infiltration in the PC patients with subtype A was higher and mainly enriched in the metabolic and conduction related pathways as compaired with the patients with subtype B. The mean risk score of 177 patients with PC was 1.921, including 157 cases in the high-risk group and 20 cases in the low-risk group. The risk score of patients with subtype B was higher than that of patients with subtype A (t=14.031, P<0.001). The overall survival of the low-risk group was better than that of the high-risk group (χ2=17.058, P<0.001), and the TMB value of the PC patients with high-risk was higher than that of the PC patients with low-risk (t=5.642, P=0.014). The mean TMB of 161 patients with somatic mutation data was 2.767, including 128 cases in the high-TMB group and 33 cases in the low-TMB group. The overall survival of patients in the high-TMB group was worse than that of patients in the low-TMB group (χ2=7.425, P=0.006). ConclusionDRGs are closely related to the prognosis and immunotherapy response of patients with PC, and targeted treatment of DRGs might potentially provide a new idea for the diagnosis and treatment of PC.
Quantitatively analyzing hematoxylin & eosin (H&E) histopathology images is an emerging field attracting increasing attentions in recent years. This paper reviews the application of computer-aided image analysis in breast cancer prognosis. The traditional prognosis based on H&E histopathology image for breast cancer is firstly sketched, followed by a detailed description of the workflow of computer-aided prognosis including image acquisition, image preprocessing, regions of interest detection and object segmentation, feature extraction, and computer-aided prognosis. In the end, major technical challenges and future directions in this field are summarized.
ObjectiveTo summarize the relationship between exosome and thyroid diseases.MethodThe literatures reports on exosomes and the physiology, pathology and diseases of thyroid were collected and reviewed.ResultsExosomes were secreted by cells and could be found in various body fluids, which could mediate the normal physiological development of the thyroid gland and play an important role in the progression of Graves’ disease. Exosomes could be used as diagnostic and differential diagnostic biomarkers for thyroid cancer and affect the growth, invasion, and metastasis of thyroid cancer. As a drug carrier for anti-thyroid cancer, exosome had a good targeting ability.ConclusionExosomes play an important role in the development of various diseases of the thyroid gland, which have good application prospects in biomarkers for early diagnosis and prognostic evaluation, as well as targeted drug carriers for thyroid cancer.
Objective To explore the association between C-reactive protein (CRP) change and the prognosis of patients with stroke. Methods Individuals who were diagnosed with stroke from the 2011 China Health and Retirement Longitudinal Study (CHARLS) registry were included. The baseline characteristics in 2011, blood tests in 2011 and 2015, and follow-up data in 2018 were collected. The patients were divided into three groups according to their CPR change from 2011 to 2015, and the cut-off values of CRP change were 0 and 5 mg/L. Logistic regression analysis was performed to evaluate the association between CRP change and the risk of death after stroke. Results A total of 1065 participants diagnosed in 2011 were enrolled. There were 383 participants in the CRP decreased group (CRP change ranging from –74.30 to –0.01 mg/L), 584 participants in the CRP stable group (CRP change ranging from 0 to 4.98 mg/L), and 98 participants in the CRP increased group (CRP change ranging from 5.00 to 79.27 mg/L). By 2018, the numbers (rates) of deaths in CRP decreased group, CRP stable group, and CRP increased group were 25 (6.53%), 33 (5.65%), and 13 (13.27%), respectively, and the difference in the mortality among the three groups was statistically significant (P=0.020). Logistic regression analysis showed that the CRP change≥5 mg/L was associated with a higher risk of death after stroke [odds ratio=2.332, 95% confidence interval (1.099, 4.946), P=0.027]. Conclusions Increasing CRP levels over time may indicate an increased risk of death in stroke patients. A 4-year increase in CRP greater than 5 mg/L may be an independent predictor of the risk of long-term death in stroke patients.
ObjectiveTo explore the association of pretreatment hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer (NSCLC) patients. MethodsThe PubMed, EMbase, Web of Science, VIP, CNKI and WanFang databases were searched from the inception to July 12, 2021 for relevant literatures. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS) score. The relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were combined to assess the relationship between pretreatment hyponatremia and clinicopathological and prognostic characteristics. The prognostic indicators included the overall survival (OS) and progression-free survival (PFS). All statistical analysis was conducted by the STATA 15.0 software. ResultsA total of 10 high-quality studies (NOS score≥6 points) involving 10 045 patients were enrolled and all participants were from Asian or European regions. The pooled results demonstrated that male [RR=1.18, 95%CI (1.02, 1.36), P=0.026], non-adenocarcinoma [RR=0.86, 95%CI (0.81, 0.91), P＜0.001] and TNM Ⅲ-Ⅳ stage [RR=1.17, 95%CI (1.12, 1.21), P＜0.001] patients were more likely to experience hyponatremia. Besides, pretreatment hyponatremia was significantly related to worse OS [HR=1.83, 95%CI (1.53, 2.19), P＜0.001] and PFS [HR=1.54, 95%CI (1.02, 2.34), P=0.040]. Pretreatment hyponatremia was a risk factor for poor prognosis of NSCLC patients. ConclusionMale, non-adenocarcinoma and advance stage NSCLC patients are more likely to experience hyponatremia. Meanwhile, the pretreatment sodium level can be applied as one of the prognostic evaluation indicators in NSCLC and patients with hyponatremia are more likely to have poor survival. However, more researches are still needed to verify above findings.
ObjectiveTo systematically evaluate the potential value of C-reactive protein to albumin ratio (CAR) as an indicator of prognosis and survival in patients with pancreatic cancer. MethodsThe literatures were searched comprehensively in the PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang, CNKI, and CQVIP databases from the establishment of the databases to May 20, 2021. The combined hazard ratio (HR) and 95% confidence interval (95%CI) were used to evaluate the correlation between the CAR and the overall survival (OS), progression-free survival (PFS), or disease-free survival (DFS) in the patients with pancreatic cancer. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of the non-randomized controlled studies, and the Stata SE 15.0 software was used for meta-analysis. ResultsA total of 2 985 patients with pancreatic cancer were included in this meta-analysis of 15 studies. The results of meta-analysis showed that the higher CAR value, the shorter OS [effect size (ES)=0.60, 95%CI (0.50, 0.69), Z=12.04, P<0.001], DFS [ES=0.63, 95%CI (0.47, 0.78), Z=3.61, P<0.001], and PFS [ES=0.41, 95%CI (0.19, 0.63), Z=7.91, P<0.001] in the patients with pancreatic cancer. The results of subgroup analysis of OS according to different countries, sample size, mean age, follow-up time, CAR cut-off value, and NOS score showed that the higher CAR value was related to the shorter OS (P<0.05). The result of linear regression analysis showed that there was no correlation between the CAR cut-off value and lnHR of OS (r2=0.947, P=0.455). Conclusion From results of this study, CAR is closely related to OS of patients, and it is expected to be used as a new reference index for monitoring and judging prognosis of patients with pancreatic cancer.
ObjectiveTo compare the clinicopathological characteristics of breast invasive micropapillary carcinoma (IMPC) with different composition ratios, and analyze the relationship between proportion of micropapillary carcinoma components and the prognosis of IMPC. Methods The related data of 121 patients with invasive ductal carcinoma (IDC) complicated with IMPC who were treated in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from August 2016 to August 2020 were collected. With micropapillary carcinoma accounting for 50%, the patients were divided into IMPC <50% group and IMPC ≥50% group. The correlation between related clinicopathological features and prognosis of patients was analyzed. Results There were 85 patients in the IMPC <50% group and 36 patients in the IMPC ≥50% group. The analysis results showed that there was no significant differences between the two groups in menstrual status, histological grade, molecular typing, TNM stage, age, immunohistochemical expression, neoadjuvant therapy, nerve invasion, nipple invasion, and skin invasion (P>0.05). The rate of lymphatic vessel invasion (LVI) in the IMPC ≥50% group was 83.33% (30/36), which was significantly higher than 61.18% (52/85) in the IMPC <50% group, and the difference between the two groups was statistically significant (χ2=5.684, P=0.017). Kaplan-Meier survival curve was drawn, and the analysis results showed that the 3-year cumulative disease-free survival (DFS) of IMPC patients was correlated with the number of lymph node metastasis and LVI (P<0.05). And with the estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular typing, proportion of micropapillary carcinoma components and histological grade were unrelated (P>0.05). The results of multivariate Cox risk regression analysis showed that the number of lymph node metastases and LVI were independent prognostic factors affecting DFS in patients. Conclusions When the proportion of IMPC component is ≥50%, the LVI rate of tumor is higher than that of IMPC component <50%. The number of lymph node metastasis and LVI are independent prognostic factors affecting DFS in IMPC patients.
Lung cancer ranks among the most prevalent and lethal malignancies globally. Its prognostic outcomes are not only contingent upon tumor characteristics and therapeutic interventions but also intricately linked to the nutritional and immune profiles of patients. This article conducts a thorough review of both domestic and international research, providing a comprehensive synthesis of the prognostic value of widely investigated nutritional and immune indicators in the context of lung cancer. The primary objective is to identify optimal prognostic markers in clinical practice, offering guidance for precise post-treatment assessment and early intervention for lung cancer patients.
Objective To systematically evaluate the prognostic prediction model for chronic heart failure patients in China, and provide reference for the construction, application, and promotion of related prognostic prediction models. Methods A comprehensive search was conducted on the studies related to prognostic prediction model for Chinese patients with chronic heart failure published in The Cochrane Library, PubMed, EMbase, Web of Science, CNKI, VIP, Wanfang, and the China Biological Medicine databases from inception to March 31, 2023. Two researchers strictly followed the inclusion and exclusion criteria to independently screen literature and extract data, and used the prediction model risk of bias assessment tool (PROBAST) to evaluate the quality of the models. Results A total of 25 studies were enrolled, including 123 prognostic prediction models for chronic heart failure patients. The area under the receiver operating characteristic curve (AUC) of the models ranged from 0.690 to 0.959. Twenty-two studies mostly used random splitting and Bootstrap for internal model validation, with an AUC range of 0.620-0.932. Seven studies conducted external validation of the model, with an AUC range of 0.720-0.874. The overall bias risk of all models was high, and the overall applicability was low. The main predictive factors included in the models were the N-terminal pro-brain natriuretic peptide, age, left ventricular ejection fraction, New York Heart Association heart function grading, and body mass index. Conclusion The quality of modeling methodology for predicting the prognosis of chronic heart failure patients in China is poor, and the predictive performance of different models varies greatly. For developed models, external validation and clinical application research should be vigorously carried out. For model development research, it is necessary to comprehensively consider various predictive factors related to disease prognosis before modeling. During modeling, large sample and prospective studies should be conducted strictly in accordance with the PROBAST standard, and the research results should be comprehensively reported using multivariate prediction model reporting guidelines to develop high-quality predictive models with strong scalability.