Development and validation of a novel mRNA signature for predicting early relapse in non-small cell lung cancer.

BACKGROUND: Recurrence after initial primary resection is still a major and ultimate cause of death for non-small cell lung cancer patients. We attempted to build an early recurrence associated gene signature to improve prognostic prediction of non-small cell lung cancer. METHODS: Propensity score matching was conducted between patients in early relapse group and long-term survival group from The Cancer Genome Atlas training series (N = 579) and patients were matched 1:1. Global transcriptome analysis was then performed between the paired groups to identify tumour-specific mRNAs. Finally, using LASSO Cox regression model, we built a multi-gene early relapse classifier incorporating 40 mRNAs. The prognostic and predictive accuracy of the signature was internally validated in The Cancer Genome Atlas patients. RESULTS: A total of 40 mRNAs were finally identified to build an early relapse classifier. With specific risk score formula, patients were classified into a high-risk group and a low-risk group. Relapse-free survival was significantly different between the two groups in both discovery (HR: 3.244, 95% CI: 2.338-4.500, P < 0.001) and internal validation series (HR 1.970, 95% CI 1.181-3.289, P = 0.009). Further analysis revealed that the prognostic value of this signature was independent of tumour stage, histotype and epidermal growth factor receptor mutation (P < 0.05). Time-dependent receiver operating characteristic analysis showed that the area under receiver operating characteristic curve of this signature was higher than TNM stage alone (0.771 vs 0.686, P < 0.05). Further, decision curve analysis curves analysis at 1 year revealed the considerable clinical utility of this signature in predicting early relapse. CONCLUSIONS: We successfully established a reliable signature for predicting early relapse in stage I-III non-small cell lung cancer.

Diagnosis and treatment of postoperative bleeding in patients after gastrectomy: a retrospective case series study.

Background: There are significant differences in terms of the pathophysiology and clinical manifestations between intra- and extra-luminal bleeding, and it is also difficult to determine the reasonable management of the bleeding. This study is to analyze the clinical characteristics of postoperative bleeding in gastric cancer, and to explore the management of postoperative intra-intestinal and extra-intestinal bleeding. Methods: We collected the clinical data of 2,978 patients with gastric cancer from the Department of Surgery, Fujian Cancer Hospital, from May 2014 to September 2019. A total gastrectomy or a distal or proximal subtotal gastrectomy with regional lymph node dissection (D1+ or D2) was included. The clinic data and management of both early (postoperative days ≤6 d) and delayed (postoperative days ≥7 d) post-operative hemorrhage were explored. This retrospective study is to compare the clinical characteristics and treatment of intra-intestinal and extra-intestinal hemorrhage. Results: The incidence of postoperative bleeding in gastric cancer was 2.85% (n=85), and the bleeding-related mortality was 4.7% (4/85). There were 67 men and 18 women, and four patients died, with a bleeding-related mortality rate of 4.7%. There were 46 cases of intra-intestinal hemorrhage and 39 cases of extra-intestinal hemorrhage. The reoperation rate in the extraneous bleeding group was higher than that in the intra-intestinal bleeding group (66.67% vs. 19.57%, P<0.001), and the incidence of delayed bleeding in the extra-intestinal bleeding group was higher than that in the intra-intestinal bleeding group (46.15% vs. 8.70%, P<0.001). In the delayed phase, 11 patients underwent reoperation to stop the bleeding, and three patients died due to bleeding-related complications. Hemostasis was successfully achieved in four patients by transcatheter arterial embolization (TAE). In the reoperation group, 72.73% (8/11) suffered hemodynamic instability and 63.64% (7/11) had an abdominal infection, while in the TAE group, 25% (1/4) had hemodynamic instability and 50% (2/4) had an abdominal infection. Conclusions: A greater number of gastric cancer patients with intra-intestinal hemorrhage are treated conservatively, while more patients with extra-intestinal hemorrhage are treated by reoperation. External bleeding is more likely to occur in the delayed period of bleeding. TAE is a safe and effective means of hemostasis if the hemodynamics is stable.

The relationship between cancer-related fatigue, quality of life and pain among cancer patients.

Objectives: This study aimed to select patients with cancer-related pain to further analyze the relationship between pain severity, fatigue severity, and quality of life. Methods: A cross-sectional study was conducted. A convenience sampling method was used to select 224 patients with cancer-related pain who were undergoing chemotherapy and met the inclusion criteria in two hospitals of two provinces from May to November 2019. All participants were invited to complete a general information questionnaire, the Brief Fatigue Inventory (BFI), the Numerical Rating Scale (NRS) for pain intensity, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: In the 24 h before completing the scales, 85 patients (37.9%) had mild pain, 121 (54.0%) had moderate pain, and 18 (8.0%) had severe pain. In addition, 92 (41.1%) patients had mild fatigue, 72 (32.1%) had moderate fatigue, and 60 (26.8%) had severe fatigue. Most patients with mild pain only experienced mild fatigue, and their quality of life was also at a moderate level. Patients with moderate and severe pain mostly had moderate or higher levels of fatigue and a lower quality of life. There was no correlation between fatigue and quality of life in patients with mild pain (r = -0.179, P = 0.104). There was a correlation between fatigue and quality of life in patients with moderate and severe pain (r = -0.537, P < 0.01; r = -0.509, P < 0.05). Conclusions: Patients with moderate and severe pain have more fatigue symptoms and lower quality of life than those with mild pain. Nurses should pay more attention to patients with moderate and severe pain, explore the interaction mechanism between symptoms, and carry out joint symptom intervention to improve the quality of life of patients.

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy.

Background: Esophageal squamous cell cancer (ESCC) is an aggressive cancer with high incidence and mortality. It is crucial to predict prognosis of these patients individually. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic indicator in several tumors, including esophageal cancer. Besides inflammatory factors, nutritional status can impact survival of cancer patients. Albumin (Alb) concentration is an easily obtained indicator to reflect nutritional status. Methods: In this study, we retrospectively collected the data of patients with ESCC and used univariate and multivariate analysis to investigate the relationship between combination of NLR and Alb (NLR-Alb) and survival. Meanwhile, we compared clinical features among NLR-Alb cohorts. Results: Univariate analysis showed that age (P=0.013), gender (P=0.021), surgical type (P=0.031), preoperative therapy (P=0.007), NLR-Alb (P=0.001), and tumor-node-metastasis (TNM) status (P<0.001) were associated with 5-year overall survival (OS). In multivariate analysis, NLR-Alb [hazard ratio (HR) =2.53, 95% confidence interval (95% CI): 1.38-4.63, P=0.003] and TNM status (HR =4.76, 95% CI: 3.09-7.33, P<0.001) were independent predictive factors for 5-year OS. The 5-year OS rates were 83%, 62%, and 55% for NLR-Alb 1, NLR-Alb 2, and NLR-Alb 3, respectively (P=0.001). Conclusions: In summary, pre-operative NLR-Alb is a favorable and cost-effective index to predict prognosis of patients with ESCC individually.

Mitophagy-related gene signature predicts prognosis, immune infiltration and chemotherapy sensitivity in colorectal cancer.

BACKGROUND: Mitophagy plays essential role in the development and progression of colorectal cancer (CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown. AIM: To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients. METHODS: Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database (GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was generated using data from the Genomics of Drug Sensitivity in Cancer database. RESULTS: Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster III patients with the most favorable prognosis. Next, a risk model based on mitophagy-related genes was developed. Patients in training and validation sets were categorized into low-risk and high-risk subgroups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil) compared to high-risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy. CONCLUSION: We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients' prognosis and response to chemotherapy in CRC. These interesting findings would provide new insight into the therapeutic management of CRC patients.

Combination of the platelet-to-lymphocyte ratio and fibrinogen may predict 5-year overall survival of patient in non-small cell lung cancer treated with surgery.

Background: Non-small cell lung cancer (NSCLC) is a major type of lung cancer with high incidence and mortality. Systemic inflammatory response (SIR) and an imbalance of the coagulation system are both associated with the tumor progression. However, few studies have investigated the prognostic utility of a combination of inflammation and the coagulation system in NSCLC. The combination of platelet-to-lymphocyte ratio (PLR) and fibrinogen (FIB) (PLR-FIB; defined as PLR × FIB) is an indicator reflecting SIR and coagulation concurrently, which have potentiality to predict prognosis of NSCLC. Methods: This retrospective, single-center study included 314 NSCLC patients with surgery. According to a cutoff value for the PLR-FIB, we divided participants into a low-PLR-FIB group and a high-PLR-FIB group. We retrospectively collected the data on 314 patients and used univariate and multivariate analyses to investigate the relationship between the PLR-FIB and survival. Results: Univariate analysis showed that adenosquamous carcinoma (ASC) (P=0.002), high PLR-FIB (P=0.023), and tumor-node-metastasis (TNM) stage III-IV (P<0.001) were associated with a poor outcome. On multivariate analysis, low PLR-FIB [hazard ratio (HR), 0.587; 95% confidence interval (CI): 0.359-0.985; P=0.044], and TNM stage I-II (HR, 0.380; 95% CI: 0.245-0.590; P<0.001) were independent factors of a better prognosis. ASC type was an independent prognostic factor of poor outcome (HR, 5.513; 95% CI: 1.895-16.034; P=0.002). There were no significant differences in patient demographics or clinical characteristics between the two PLR-FIB groups (P>0.05). The 5-year overall survival (OS) rates were 80.8% and 67.9% for the low-PLR-FIB group and high-PLR-FIB group, respectively (P=0.02). Conclusions: Preoperative PLR-FIB was found to be an independent prognostic factor for 5-year overall survival in patients with NSCLC treated with surgery.

Clinical characteristics of fever clinic visits during the coronavirus disease 2019 pandemic: a retrospective case-control study.

Background: Little is known about the change in characteristics of fever-clinic visits during the coronavirus disease 2019 (COVID-19) pandemic. We sought to examine the changes in the volume, characteristics, and outcomes of patients presenting at a fever clinic duringclinic during the first-level response to COVID-19. Methods: We conducted a single tertiary-center retrospective case-control study. We included consecutive patients aged 14 years or older who visited the fever clinic of a tertiary hospital during the period of the first-level response to the COVID-19 pandemic in Fuzhou, China (from 24 January to 26 February 2020). We also analyzed the data of patients in the same period of 2019 as a control. We compared a number of outcome measures, including the fever clinic volumes, consultation length, proportion of patients with pneumonia, hospital admission rate, and in-hospital mortality, using the fever-clinic visit data during the two periods. Results: We included 1,013 participants [median age: 35; interquartile range (IQR): 27-50, 48.7% male] in this retrospective study, including 707 in 2020 and 306 in 2019. The median daily number of participants who presented at the fever clinic in 2020 was significantly higher than that in 2019 [18 (IQR: 15-22) vs. 13 (IQR: 8-17), P=0.001]. Participants in 2020 had a longer consultation length than those in 2019 [127 (IQR: 51-204) vs. 20 (IQR: 1-60) min, P<0.001]. Participants in 2020 were also more likely to be diagnosed with acute pneumonia than those in 2019 [168 (23.8%) vs. 40 (13.1%), P<0.001]. The hospital admission rate in 2020 was higher than in 2019 [73 (10.3%) vs. 13 (4.2%), P=0.001]. No significant difference was found in terms of the in-hospital mortality of participants in 2020 and 2019 [8 (1.1%) vs. 0, P=0.114]. Conclusions: Our findings suggest a higher visits volume, proportion of acute pneumonia, and hospital admission rate among patients presenting at fever clinic during the COVID-19 pandemic. Improved measures need to be implemented.

Local surgery improves survival in elderly patients with stage IV breast cancer: a population-based retrospective cohort study.

Background: Little is known about the role of local therapy in elderly patients with stage IV breast cancer. This study aimed to evaluate the effect of local therapy including surgery and radiotherapy in this kind of population by using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Eligible patients diagnosed between 2010 and 2015 were selected from the SEER database. Baseline characteristics, way of local therapy and survival information were collected for survival and analysis of prognostic factors. Cause-specific survival (CSS) curves were calculated using the Kaplan-Meier (KM) method and compared by the log-rank test. Cox regression and multivariate competing risk analyses were used to analyze prognosis factors. Results: A total of 1,900 patients were enrolled with the median age of 71 (range, 65 to 95) years. The 5-year CSS of patients with surgery was significantly better than that of those who did not (36.5% vs. 22.4%, P<0.001). Moreover, surgery was an independent protective factor for CSS in both multivariate Cox regression analysis [hazard ratio (HR), 0.588; 95% confidence interval (CI), 0.485-0.643; P<0.001] and multivariate competing risk analysis [subdistribution HR (SHR), 0.620; 95% CI, 0.535-0.718; P<0.001]. Stratified analysis showed that most subgroup patients could benefit from surgery. The 5-year CSS of patients with radiotherapy was comparable to those without radiotherapy (28.9% vs. 26.5%, P=0.060), and radiotherapy was not an independent prognostic factor for CSS (SHR, 1.005; 95% CI, 0.846-1.202; P=0.954). However, subgroup analysis found that patients with moderate grade in histopathology, luminal A, or triple-negative breast cancer (TNBC) subtype could benefit from radiotherapy (all P<0.05). Conclusions: Elderly patients with stage IV breast cancer can benefit from surgical treatment. This study helps to select the appropriate group for local surgery or radiotherapy according to the personal situation of the elderly to obtain the maximum benefit.

TRPV3 inhibits colorectal cancer cell proliferation and migration by regulating the MAPK signaling pathway.

Background: The aim of this study was to investigate the inhibiting effect of transient receptor potential vanilloid 3 (TRPV3) on the proliferation and migration of colorectal cancer (CRC) cells and to explore the underlying mechanism. Methods: A microarray dataset from the publicly available Gene Expression Omnibus (GEO) database was used to investigate the prognostic value of TRPV3 in CRC. In addition, 100 CRC tissue samples were collected at our center to further validate its prognostic value at the protein level. Cell proliferation ability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell migration ability was detected by transwell assay. Gene set variation analysis (GSVA) was performed to identify the potential pathways regulated by TRPV3. Results: Based on the largest microarray dataset (GSE39582), low expression of TRPV3 was found to be significantly associated with poor prognosis in CRC patients, and this result was successfully validated at our cancer center. Functional experiments showed that knockdown of TRPV3 enhanced cell proliferation and migration, while enforced TRPV3 expression exhibited the opposite effect. GSEA based on public microarray data revealed that the mitogen-activated protein kinase (MAPK) signaling pathway was notably activated in patients with low expression of TRPV3. Further experiments in vivo confirmed that TRPV3 silencing promoted cell proliferation and migration by activating the MAPK signaling pathway. Conclusions: Low expression of TRPV3, which stimulates cell proliferation and migration by provoking the MAPK signaling pathway, indicated poor prognosis in CRC patients.

Combination of albumin concentration and neutrophil-to-lymphocyte ratio for predicting overall survival of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer contributes significantly to the total of cancer-linked deaths globally, accounting for 1.3 million deaths each year. Preoperative albumin (Alb) concentration and neutrophil-to-lymphocyte ratio (NLR) may reflect chronic inflammation and be used to predict lung cancer outcomes. METHODS: The clinical records of 293 patients with non-small cell lung cancer (NSCLC) in Fujian Medical University Cancer Hospital & Fujian Cancer Hospital were reviewed retrospectively in this current study. Clinicopathologic pretreatment, including NLR, Glasgow prognostic score (GPS), and post-treatment value, such as tumor-node-metastasis (TNM) were documented. The cut-off finder application was employed to calculate the optimal threshold values. The significance of Alb concentration combined with NLR (COA-NLR) on the prediction of overall survival (OS) was explored using Kaplan-Meier analysis along with Cox proportional hazards. RESULTS: The results revealed that COA-NLR could independently assess the OS of patients with NSCLC [hazard ratio (HR) =1.952, 95% confidence interval (CI): 1.367 to 2.647, P<0.001]. Moreover, the 3-year OS rates were 87.2%, 68.5%, and 52.8% for the COA-NLR =0, COA-NLR =1, and COA-NLR =2, respectively (P<0.001). CONCLUSIONS: Preoperative COA-NLR value can effectively stratifies prognosis in NSCLC patients by classified patients into three independent groups. It can be adopted as an effective biomarker for prognosis in NSCLC patients treated with resection.

[Inhibiting effects of interleukin-10 on expression of E-selectin and L-selectin in cerebral ischemia-reperfusion: experiment with rats].

OBJECTIVE: To investigate the inhibiting effects of interleukin-10 (IL-10) on the expression of E-selectin and L-selectin in cerebral ischemia-reperfusions. METHODS: Seventy-two adult male Sprague-Dawley rats were randomly divided into 4 equal groups, cerebral ischemia-reperfusion (I/R) group undergoing middle cerebral artery occlusion with Longa's thread method, IL-10 group undergoing lateral ventricle injection of IL-10 after the establishment of I/R model, Vehicle group undergoing lateral ventricle injection of normal saline after the establishment of I/R model, and sham operation (Sham) group. Twenty-four hours later the rats were killed with their brains taken out. Immunohistochemistry, RT-PCR and Western blotting were used to detect the mRNA and protein expression of E-selectin and L-selectin. RESULTS: The E-selectin and L-selectin expression levels of the I/R group were significantly up-regulated compared with the Sham group (both P < 0.05). The numbers of E-selectin and L-selectin positive vessels of the IL-10 group were 18.8 +/- 1.9/10 HP fields and 15.8 + 2.4/10 HP fields respectively, both significantly less than those of the vehicle group (24.7 +/- 2.4/10 HP fields and 20.9 + 3.3/10 HP fields respectively, both P < 0.05). The E-selectin and L-selectin gene mRNA expression levels of the IL-10 group were (0.431 +/- 0.029) and (0.318 +/- 0.048) respectively, both significantly lower than those of the Vehicle group [(0.497 +/- 0.019) and (0.433 +/- 0.087) respectively, both P < 0.05]. The E-selectin and L-selectin protein expression levels of the IL-10 group were (0.349 +/- 0.037) and (0.296 +/- 0.035) respectively, both significantly lower than those of the Vehicle group [(0.421 +/- 0.043,) and (0.348 +/- 0.044) respectively, both P < 0.05]. CONCLUSIONS: IL-10 suppresses the expression of E-selectin and L-selectin in cerebral ischemia-reperfusion.

[Effects of bone marrow-derived mesenchymal stem cells transplantation on recovery of neurological functions and expression of synaptophysin in focal cerebral infarction in rats].

AIM: To investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) transplantation on the recovery of neurological functions and the expression of synaptophysin in focal cerebral infarction in rats. METHODS: 72 male adult Sprague-Dawley rats were randomly divided into 4 groups (18 in each group): shamoperated group, middle cerebral artery occlusion (MCAO) roup,vehicle group and MCAO+BMSC-treated group. A permanent focal cerebral ischemia model was established using modified Longa's method. BMSC was labeled by DAPI before the transplantation. One day after right middle cerebral artery occlusion(MCAO), 1 x 10(6) cells were injected into the lateral ventricle of rats in BMSCs-treated group and the same dose of PBS was given to the rats in vehicle group. Before sacrificed and at 4 d, 7 d and 14 d after MCAO, the neurological functions were tested by balance beam, rota-rod and screen prehensile and the synaptophysin was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical method. RESULTS: DAPI stained positive cells were observed around the cerebral infarcted area in the BMSC-treated group. Compared with the MCAO group and the vehicle group,the neurological functions in BMSC-treated group were better on 7 d and 14 d after MCAO (P<0.05 or P<0.01), and the synaptophysin around the cerebral infarcted area was significantly upregulated on 4 d, 7 d and 14 d after MCAO (all P<0.01). CONCLUSION: BMSC transplantation can improve the neurological functions by upregulating the expression of synaptophysin after MCAO in rats.

[Effects of adipose-derived stem cell transplantation on the angiogenesis and the expression of bFGF and VEGF in the brain post focal cerebral ischemia in rats].

AIM: To investigate the effects of adipose-derived stem cell (ADSC) transplantation on the angiogenesis in the brain post focal cerebral ischemia in rats. METHODS: 72 male adult Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, middle cerebral artery occlusion (MCAO) group, vehicle group and MCAO+ADSC-treated group (n=18). A permenant focal cerebral ischemia model was established with the modified Longa's method. ADSC were labeled by DAPI before transplantation. One day after right MCAO, 30 muL of cell suspension containing 1x10(6) cells were injected into the lateral ventricle of MCAO+ADSC-treated group and the same dose of PBS was given to the vehicle group. On D4, D7 and D14 after MCAO, the rats were killed to detect the regeneration of microvessel and the expression of bFGF and VEGF in ischemic region by immunohistochemistry and RT-PCR. RESULTS: A lot of microvessel proliferate in the injured cortex reached peak in 2 weeks. The microvessel density in the brain tissues of rats treated with ADSC was higher than that in MCAO group and vehicle group (P<0.01). The expression of bFGF and VEGF in the brain tissues of MCAO+ADSC-treated group was higher than that in MCAO group and vehicle group on D4, D7 and D14 post MCAO. CONCLUSION: The transplantation of ADSC can promote the revascularization of cerebral ischemia in rats partly by enhancing bFGF and VEGF synthesis in brain.