Independent Risk Factor For OS Research Articles

Mutational Spectrum and Prognosis Analysis of AML Patients Based on High-Throughput Sequencing

To investigate the mutational spectrum and its prognostic significance in patients with acute myeloid leukemia (AML). The clinical data of 93 patients with newly diagnosed AML who underwent gene mutation detection by high-throughput sequencing (HTS) from March 2014 to April 2018 in our hospital was analyzed retrospectively. The distribution of mutant genes was summarized and the prognostic factors for intermediate-risk acute myeloid leukemia (IR-AML) were analyzed. Among 93 AML patients, 88.17% had at least one gene mutation, and 53.76% patients showed more than one recurrent genetic mutation. CEBPA showed the highest mutation frequency (20.4%), followed by ASXL1, TET2, NRAS, FLT3-ITD, NPM1, IDH2, DNMT3A, and their mutation frequency were higher than 10%. IDH1/2 and NPM1, ASXL1 and U2AF1, FLT3 and NPM1 often co-occured (P < 0.05). In the prognosis analysis of 57 patients with IR-AML, the IDH2 mutation related with poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). The prognosis analysis of IR-AML patients showed that age≥50 years, WBC >100×109/L, anemia, and CD22+ were independent risk factors for OS. Age≥50 years , WBC >100×109/L, anemia, CD34+, IDH2 mutation were independent risk factors for PFS. There are co-occurring mutation patterns between the mutated genes. IDH2 mutations relates with poor prognosis and possesses potential to be molecules for model of IR-AML prognostic stratification. Genetic testing based on HTS contributes to revealing the pathogenic mechanism of AML, and is significant for evaluating the prognosis of patients with AML.

Impact of Intraoperative Blood Loss on the Survival of Patients With Stage II/III Colorectal Cancer: A Multicenter Retrospective Study.

Resection of the primary lesion with radical lymph node dissection is the most promising treatment avenue for patients with cancer. On the other hand, these procedures often induce excessive intraoperative blood loss (IBL) and require perioperative blood transfusion. The influence of IBL on the long-term postoperative outcomes of patients with digestive cancer is controversial. We investigated the impact of IBL on survival and recurrence after curative surgery in patients with colorectal cancer (CRC) in a single study group. In total, 1,597 patients who underwent radical resection for CRC at three group hospitals between 2000 and 2019 were reviewed. Patients were classified into a group with high IBL (≥200 ml) or low IBL (<200 ml). The risk factors for disease-free (DFS) and overall (OS) survival were analyzed. A total of 489 and 1,108 patients were classified into the high and low IBL groups, respectively. The OS and DFS rates at 5 years after surgery were 89.3% and 63.4%, respectively, for the high IBL group and 96.9% and 77.8% for the low IBL group; these differences were statistically significantly (p<0.001). The multivariate analysis demonstrated that IBL was a significant independent risk factor for OS and DFS. The amount of IBL was associated with significant differences in the OS and DFS of patients with stage II/III CRC who received curative resection. The surgical procedure, surgical strategy, and perioperative care should be carefully planned to avoid causing IBL.

Positive vein groove margin does not affect survival in patients undergoing pancreatoduodenectomy for early stages of pancreatic ductal adenocarcinoma

Presenter: Manish Ahuja MBBS, DNB | University Hospitals Birmingham NHS Trust Background: The prognostic significance of portal/superior mesenteric vein (PV/SMV) groove involvement after pancreaticoduodenectomy (PPPD) for pancreatic ductal adenocarcinoma (PDAC) is controversial. Following adoption of the reporting guidelines by the Royal College of Pathologists (R1: tumour margin < 1mm), R1 reporting rates have increased which are considered to impact the overall survival. The aim of this study was to investigate the significance of R1 vein groove margin on overall (OS) and disease-free survival (DFS) after pancreaticoduodenectomy (PD) for early stage pancreatic ductal adenocarcinoma (PDAC). Methods: This is a single centre retrospective study including all resections performed for resectable and borderline with venous only involvement (BR-V) PDAC of the head and uncinate process over a 10-year period (2011-2020). Statistical investigation was performed with descriptive statistics and Kaplan Meier and univariate and multivariate Cox regression survival analysis. Results: Two hundred patients underwent PD for resectable (n = 117, 59%) or BR-V (n = 83, 41%) tumours. Vein resection was performed in 102 (51%) cases. Pathological staging of the tumours was pT1 11 (6%), pT2 122 (61%) and pT3 67 (33%) cases; and pN0 18 (9%) pN1 101 (51%) pN2 81 (40%) cases. Clear surgical margins were observed in 35 (17%) cases. In 34 (17%) cases the vein groove margin was the only positive margin reported (VG+). Median follow-up was 14 months (range: 1-83). OS was significantly better in cases with clear margins (p = 0.006) (Picture 1a). No difference in OS was identified between VG+ only patients and those with negative margins (p = 0.129) or those with multiple sites of margin positivity (p = 0.172). Cox regression analysis did not identify VG+ only margin as an independent predictor of OS (Table 1). In a multivariate model investigating the surgical margins separately, the posterior, SMA and pancreas transection margins, as well as perineural invasion and adjuvant chemotherapy were identified as independent predictors of OS. DFS was significantly better if surgical margins were clear (p = 0.014) (Picture 1b). A trend to worse DFS was identified in patients with VG+ margin only compared to those with negative margins (p = 0.058). No difference in DSF was observed between VG+ only patients and those with multiple sites of margin positivity (p = 0.608). Cox regression analysis did not identify VG+ only margin as an independent predictor of DFS (Table 1). In a multivariate model investigating the surgical margins separately, the SMA margin was the only margin along with adjuvant chemotherapy that independently predicted DFS. Conclusion: Vein groove margin positivity doesn’t affect OS but may affect DFS after PD in patients with resectable and BR-V PDAC. In contrast, the posterior and pancreas transection margins along with PNI were identified as independent risk factors for OS. The SMA margin and adjuvant chemotherapy were independent factors for both OS and DFS.

Prognostic significance of different IDH mutations and accompanying gene mutations in patients with acute myeloid leukemia

目的探讨IDH不同突变亚型及伴发不同基因突变在非M3型急性髓系白血病（AML）患者中的预后意义。方法采用二代测序技术检测2016年6月至2018年12月就诊于郑州大学第一附属医院的389例AML患者的22种基因突变情况，通过Kaplan-Meier法及Cox回归模型分析影响预后的因素。结果389例AML患者中，IDH1及IDH2的突变率分别为6.2%、8.7%，未发现IDH1与IDH2共突变的情况。IDH2突变型患者年龄偏大、骨髓原始细胞比例高、正常核型多见、常合并RUNX1突变及SRSF2突变。单因素方差分析发现，IDH1突变型组较野生型组的中位总生存（OS）及无进展生存（PFS）时间明显缩短（P值均<0.05）；IDH2突变作为一个单变量对预后无显著影响，不同突变位点对预后的影响不同，IDH2R140突变对预后无显著影响，IDH2R172突变型患者较IDH2野生型患者完全缓解（CR）率明显减低、中位OS及PFS时间明显缩短（P值均<0.05）。在正常核型或年龄≥50岁的患者中，IDH不同突变亚型显示出同样的预后意义。74.1%（43/58）IDH突变患者同时携带其他基因突变，伴发基因突变数目对患者的预后无显著影响，IDH突变患者中伴NPM1突变者的CR率明显高于不伴NPM1突变者（81.8%对36.4%，P＝0.014），伴DNMT3A突变者的中位OS时间短于不伴DNMT3A突变者[4.0（95%CI 3.8～4.2）个月对6.3（95%CI 2.4～10.2）个月，P＝0.041]。多因素分析显示：年龄≥60岁、WBC≥100×109/L是影响患者OS及PFS的独立危险因素，2个疗程内CR、造血干细胞移植是影响患者OS及PFS的独立有利因素。结论在AML（非M3型）患者中，IDH基因突变常与其他基因突变共存，IDH不同突变亚型及伴发基因突变显示出不同的预后意义。

Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases.

Double-unit unrelated cord blood transplantation (DUCBT) is an option in patients for whom a single unit is not sufficient to provide an adequate number of cells. As current guidelines on UCB unit selection are mainly based on single-unit UCB data, we performed a retrospective analysis of 1375 adult recipients of DUCBT for hematologic malignancies to determine optimal criteria for graft selection. Cryopreserved total nucleated cells (TNCs; ≤3.5 vs >3.5 × 107/kg: hazard ratio [HR], 1.53; 30% vs 45%; P = .01), number of HLA mismatches (≥2 vs 0-1: HR, 1.28; 42% vs 48%; P = .01), and ABO compatibility (minor/major ABO incompatibility vs compatibility: HR, 1.28; P = .04) were independent risk factors for OS. Cryopreserved CD34+ cell dose ≥0.7 × 105/kg in the winning UCB was associated with improved OS (HR, 1.34; P = .03). Low TNC (≤3.5 × 107/kg) and CD34+ (≤1.4 × 105/kg) cell doses were related to decreased neutrophil recovery (HR, 0.65 [P = .01] and HR, 0.81 [P = .01], respectively). DUCBT recipients with ≥2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease (HR, 1.26 [P = .03] and 1.59 [P = .02], respectively). Low TNC dose (HR, 1.57; P = .02) and receiving UCB with ≥2 HLA mismatches (HR, 1.35; P = .03) were associated with increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.

A gene-based survival score for lung adenocarcinoma by multiple transcriptional datasets analysis

BackgroundLung adenocarcinoma (LUAD) remains a crucial factor endangering human health. Gene-based clinical predictions could be of great help for cancer intervention strategies. Here, we tried to build a gene-based survival score (SS) for LUAD via analyzing multiple transcriptional datasets.MethodsWe first acquired differentially expressed genes between tumors and normal tissues from intersections of four LUAD datasets. Next, survival-related genes were preliminarily unscrambled by univariate Cox regression and further filtrated by LASSO regression. Then, we applied PCA to establish a comprehensive SS based on survival-related genes. Subsequently, we applied four independent LUAD datasets to evaluate prognostic prediction of SS. Moreover, we explored associations between SS and clinicopathological features. Furthermore, we assessed independent predictive value of SS by multivariate Cox analysis and then built prognostic models based on clinical stage and SS. Finally, we performed pathway enrichments analysis and investigated immune checkpoints expression underlying SS in four datasets.ResultsWe established a 13 gene-based SS, which could precisely predict OS and PFS of LUAD. Close relations were elicited between SS and canonical malignant indictors. Furthermore, SS could serve as an independent risk factor for OS and PFS. Besides, the predictive efficacies of prognostic models were also reasonable (C-indexes: OS, 0.7; PFS, 0.7). Finally, we demonstrated enhanced cell proliferation and immune escape might account for high clinical risk of SS.ConclusionsWe built a 13 gene-based SS for prognostic prediction of LUAD, which exhibited wide applicability and could contribute to LUAD management.

Clinical efficacy of cyberknife in patients with primary large hepatocellular carcinoma over 70 years old

Objective: To analyze the clinical efficacy and safety of cyberknife in the treatment of patients with primary large hepatocellular carcinoma over 70 years old. Methods: A total of 82 patients (58 males and 24 females) with large hepatocellular carcinoma aged over 70 years (70 to 85 years, (75±4) years) with a median tumor diameter of 6.7 cm (5.0~10.0 cm) were retrospectively collected. All patients were diagnosed by pathology or radiography in the Cancer Radiotherapy Center of the Fifth Medical Center of the PLA General Hospital from March 2014 to December 2018, and treated with cyberknife stereotactic radiotherapy. Progression free survival rate (PFS), local control rate (LC), overall survival rate (OS) and adverse reactions were observed at 1, 2 and 3 years. Kaplan-Meier was used for survival analysis, and Cox regression model was used to analyze survival-related factors. Results: All 82 patients successfully completed radiation therapy with a median survival time of 20 months, a median PFS of 10 months, an objective response rate of 64.63% (53/82), and a disease control rate of 85.37% (70/82). After treatment, the PFS at 1, 2, and 3 years were 39.0% (32/82), 22.1% (18/82), and 17.1% (14/82), respectively; the LC at 1, 2, and 3 years were 95.1% (78/82), 92.3% (76/82), and 92.3% (76/82), respectively; and the OS at 1, 2, and 3 years were 68.3% (56/82), 48.8% (40/82) and 31.7% (26/82), respectively. Nine patients suffered from radiation-induced liver disease (RILD), and there were no deaths due to RILD. Cox regression analysis showed that alpha-fetoprotein (AFP) was an independent risk factor for OS (HR=2.304, 95%CI 1.118-4.747;P<0.05). Conclusion: Cyberknife treatment for patients with primary large hepatocellular cancer over 70 years old has higher LC and OS, better curative effect, and less treatment-related adverse reactions.

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2–7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9–64.3) and 36.4% (95% CI 27.6–47.9) at 2 years and 38.6% (95% CI 29.2–51.1) and 25.3% (95% CI 17.5–36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02–6.70) and PFS (HR 3.69, 95% CI 2.09–6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14–9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.

Low Prognostic Nutritional Index Indicates Dismal Prognosis in Patients with Diffuse Large B Cell Lymphoma

Background: Prognostic nutritional index (PNI) is calculated based on serum albumin concentration and absolute lymphocyte count, and its prognostic value has been established in various human malignancies. However, whether PNI can be applied in predicting the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains to be clarified. The aim of the present study is to explore the prognostic value of baseline PNI in DLBCL. Methods: We retrospectively reviewed the medical records of 98 patients with DLBCL treated at the Southeast University-affiliated Zhongda Hospital between January 2013 and November 2019. The optimal cut-off value of PNI was determined using a receiver operating characteristic (ROC) curve and the Youden index. The relationship of high and low PNI with the clinical characteristics of the patients and prognosis were analyzed. Results: Patients with low PNI tended to have a worse event-free survival (EFS) and overall survival (OS) (EFS, P=0.029; OS, P&lt;0.001). For patients treated with R-CHOP（Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), PNI proved to be predictive for survival (EFS, P= 0.020; OS, P&lt;0.001), while no significant effect was found in DLBCL patients who received CHOP chemotherapy (EFS, P=0.639; OS, P=0.114). Multivariate analysis showed that PNI was an independent risk factor for OS and EFS of all 98 DLBCL patients after adjusting for model a (OS: adjust for age, gender, body mass index, performance status, B symptoms, international prognostic index, hemoglobin；EFS：adjust for age, gender, Ann Arbor stage, international prognostic index, lactate dehydrogenase, treatment, absolute lymphocyte count, hemoglobin). PNI remained an independent risk factor for both OS and EFS in patients after adjusting for model b (adjust for all items). Conclusion: PNI is a simple and useful marker to predict survival outcome in DLBCL patients, and low PNI is an independent predictor of a better outcome in terms of EFS and OS outcome in DLBCL, suggesting that PNI is an effective prognostic factor in patients with DLBCL.

LRRC19—A Bridge between Selenium Adjuvant Therapy and Renal Clear Cell Carcinoma: A Study Based on Datamining

Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.

LncRNA MALAT1 Regulates the Cell Proliferation and Cisplatin Resistance in Gastric Cancer via PI3K/AKT Pathway.

BackgroundMany studies showed that long non-coding RNA MALAT1 is served as an oncogene. However, the specific role of MALAT1 in gastric cancer is not fully elucidated. The aim of this study is to elucidate the regulatory effects of MALAT1 on tumor development and cisplatin resistance in gastric cancer.MethodsTCGA database was applied to investigate the expression levels of MALAT1 in GC tissues and normal gastric tissues and its correlation with GC patients’ survival. Univariate and multivariate analysis were performed to investigate whether MALAT1 expression is an independent risk for overall survival of gastric cancer patients. The expression of MALAT1 was detected by Quantitative real-time PCR. After knockdown or overexpression of MALAT1, the cellular functions of GC cells were detected by cell-proliferation, flow cytometry, transwell assay and colony formation assays, respectively. Western blot analysis was performed to detect the protein levels of Bcl-2 and key genes in the PI3K/AKT pathway in GC cells. Finally, CCK-8 assay was performed to explore the effect of MALAT1 on cisplatin resistance of GC cells.ResultsHigher expression of MALAT1 was detected in GC tissues than that of adjacent normal tissues, high MALAT1 expression is an independent risk for overall survival of gastric cancer patients. Knockdown of MALAT1 inhibited proliferation, migration and invasion of GC cells, while overexpression of MALAT1 Overexpression of MALAT1 yielded opposite results. Western blot results showed that protein expressions of p-PI3K, p-AKT and p-STAT3 were downregulated after MALAT1 knockdown in GC cells, while these proteins were upregulated after MALAT1 overexpression. Additionally, the IC50 in MGC803/CDDP cells transfected with si-MALAT1 was lower than in those transfected with si-NC. The apoptotic rate in MGC803 cells transfected with pcDNA-MALAT1 was remarkably lower than those transfected with NC.ConclusionWe demonstrated that MALAT1 is highly expressed in GC, high MALAT1 expression is an independent risk factor for OS among GC patients. Moreover, MALAT1 promotes malignant progression of GC and contributes to cisplatin resistance of GC cells, indicating MALAT1 may serve as a biological hallmark for predicting the prognosis of GC.

The Impact of Intraoperative Blood Loss on the Survival of Patients With Stage II/III Pancreatic Cancer.

Pancreatic cancer is a fatal disease with a poor prognosis. Pancreatic cancer is often unresectable at the time of diagnosis, so the analysis of risk factors in patients with indications for surgery is important. We investigated the impact of intraoperative blood loss (IBL) on survival and recurrence in patients with stage II/III pancreatic cancer after curative surgery. This study included 76 patients who underwent curative surgery for stage II/III pancreatic cancer between 2007 and 2012. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. IBL of 1,000 ml was considered to be the optimal cut-off value for classification based on a receiver operating characteristic (ROC) curve analysis. The OS rates at 5 years after surgery in the groups with low and high IBL were 36.6% and 11.4%, respectively, which was a statistically significant difference (p=0.003). The RFS rates at 1 year after surgery were 49.8% and 24.6%, respectively, which was a significant difference (p=0.045). A multivariate analysis demonstrated that IBL was a significant independent risk factor for OS. IBL is an independent prognostic factor after curative resection of stage II/III pancreatic cancer. The reduction of bleeding during surgery is necessary to improve the results of pancreatic cancer surgery.

Pretransplant Risk Factors for Calcineurin Inhibitor-Induced Encephalopathy and Limbic Encephalitis Following Allogeneic Hematopoietic Cell Transplantation

Pretransplant Risk Factors for Calcineurin Inhibitor-Induced Encephalopathy and Limbic Encephalitis Following Allogeneic Hematopoietic Cell Transplantation

Incidence, Risk Factors, Treatment and Long Term Outcome of Refractory and First Relapse AML Patients in the OSHO Studies

Incidence, Risk Factors, Treatment and Long Term Outcome of Refractory and First Relapse AML Patients in the OSHO Studies

Potentiality of forkhead box Q1 as a biomarker for monitoring tumor features and predicting prognosis in non-small cell lung cancer.

BackgroundThis study aimed to explore the correlation of forkhead box Q1 (FOXQ1) with clinicopathological features and survival profiles in patients with non‐small cell lung cancer (NSCLC).MethodsA total of 238 NSCLC patients with TNM stage I‐III who underwent surgical resection were reviewed, and the expression of FOXQ1 in tumor and paired adjacent tissue was detected using immunohistochemistry assays. The clinical data and survival data of patients with NSCLC were retrieved and calculated.ResultsFOXQ1 expression was increased in tumor tissue (61.3% high expression and 38.7% low expression) compared with paired adjacent tissue (37.8% high expression and 62.2% low expression) (P < .001). In addition, high FOXQ1 expression was associated with larger tumor size (P = .042), lymph node metastasis (P = .040), and advanced TNM stage (P = .002). Disease‐free survival (DFS) (P = .016) and overall survival (OS) (P = .008) were both reduced in patients with high FOXQ1 expression compared with patients with low FOXQ1 expression. Additionally, high FOXQ1 expression (P = .043), poor pathological differentiation (P = .003), and lymph node metastasis (P < .001) were independent risk factors for DFS, and high FOXQ1 expression (P = .021), tumor size (>5 cm) (P = .014), and lymph node metastasis (P < .001) were independent risk factors for OS.ConclusionHigh FOXQ1 expression is associated with advanced tumor features as well as undesirable survival profiles in patients with NSCLC, implying the potential prognostic value of FOXQ1 for NSCLC.

Immunohistochemistry-Based Consensus Molecular Subtypes on Tissue Microarray as a Prognostic Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer

Background: For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial. Consensus molecular subtype (CMS) status have been validated to be a prognostic tool for colorectal cancer. In this study, CMS status was investigated as prognostic biomarkers for the efficacy of adjuvant chemotherapy for stage II colorectal cancer. Methods: The tissue microarray (TMA) was retrospectively constructed of 165 non-consecutive, primary, and sporadic stage II CRCs. CMS status was determined by immunohistochemistry staining of CDX2, HTR2B, FRMD6, and ZEB1, combining with MSI testing. The prognostic for adjuvant chemotherapy efficacy of CMS status was calculated by Kaplan-Meier curves and Cox regression analysis. Subgroup analyses were conducted according to tumor location. Findings: CMS status was associated with overall survival (OS, P=0.014) and disease-free survival (DFS, P=0.027) for stage II CRCs and it's an independent risk factor for OS (P=0.029). Among all high-risk clinicopathological factors, patients with CMS2/3 (P=0.010, HR: 0.445, 95%CI: 0.227-0.875), left-sided tumors (P=0.028, HR: 0.488, 95%CI:0.247-0.968) or <12 lymph nodes examined (P=0.015, HR: 0.307, 95%CI: 0.097-0.974) had survival benefit from adjuvant chemotherapy. No survival benefit has been observed for CMS1 or CMS4 tumors. Subgroup analysis stratified by tumor location showed that adjuvant chemotherapy only improved OS for patients with left-sided tumors of CMS2/3 subtype. Regardless of CMS subtype, right-sided tumors had no benefit from adjuvant chemotherapy. Interpretation: For stage II CRCs, CMS subtype is a better prognostic factor for adjuvant chemotherapy. Patients with left-sided tumors of CMS2/3 subtype have OS benefit by receiving adjuvant chemotherapy. Funding: This study is supported by grants from Shanghai Sailing Program (19YF1409500 to YL), Science and Technology Commission of Shanghai Municipality (18401933402 to JP) and Shanghai Natural Science Foundation (19ZR1410200 to DH). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: This study was approved by the institutional review board of FUSCC, and was carried out in accordance with the Declaration of Helsinki.

High EGFL7 expression may predict poor prognosis in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

ABSTRACTEpithelial growth factor-like 7 (EGFL7) is a secretory protein with a well-characterized role in angiogenesis and the oncogenesis of certain solid tumors. Overexpression of EGFL7 is associated with adverse prognosis in patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, whether this association persists after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To further clarify the prognostic role of EGFL7, seventy-one AML patients with EGFL7 expression data who underwent allo-HSCT from The Cancer Genome Atlas database were included and divided into either EGFL7high or EGFL7low group based on the median EGFL7 expression level. Two groups had similar clinical and molecular characteristics except that the EGFL7high group had less frequent NPM1 mutations (P= .001). Kaplan-Meier survival curves showed that high EGFL7 expressers had shorter OS than the low expressers (P= .040). Univariate analysis showed that high EGFL7 expression, MLL-PTD, RUNX1 and TP53 mutations were associated with short OS (all P< .05). Multivariate analysis indicated that high EGFL7 expression, FLT3-ITD, RUNX1 and TP53 mutations were independent risk factors for OS (all P< .05). Collectively, our study suggested that EGFL7, like the other widely-used risk stratification factors, could serve as a prognostic tool and therapeutic target in AML, even after allo-HCST.

Age-adjusted Charlson Comorbidity Index (ACCI) is a significant factor for predicting survival after radical gastrectomy in patients with gastric cancer

IntroductionTo assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict survival after radical gastrectomy in patients with gastric cancer (GC).MethodData from patients with GC who underwent radical gastrectomy from January 2008 to December 2012 in Fujian Medical University Union Hospital were retrospectively analyzed. Patients were categorized into either high ACCI group or low ACCI group based on the effect of ACCI on long-term GC prognosis. 1:1 propensity score matching (PSM) was used to reduce confounding bias. To further analyze the impact of ACCI on the long-term prognosis of patients after radical gastrectomy, a nomogram was built based on the Cox proportional hazards regression model.ResultsA total of 1476 patients were included in the analysis. After PSM, there was no statistically significant differences in tumor location, tumor size and tumor stage between low ACCI group (429 cases) and high ACCI group (429 cases) (all P > 0.05). Before and after PSM, the incidence of postoperative complications in high ACCI group was significantly higher than that in low ACCI group (P < 0.05). The 5-year overall survival rate (OS) in low ACCI group was significantly higher than that in high ACCI group. Multivariate analysis showed that ACCI was an independent risk factor for OS (P < 0.05). The Harrell’s C-statistics (C-index) of TNMA, a prognostic evaluation system combining ACCI and TNM staging system, was significantly higher than that of TNM staging system in both the modeling and validation groups (all P < 0.05).ConclusionsACCI was an independent risk factor for the long-term prognosis of GC patients after radical gastrectomy that could effectively improve the predictive efficacy of the TNM staging system for GC.

Adjuvant chemotherapy for rectal cancer with complete pathological response (pCR) may not be necessary: a pooled analysis of 5491 patients

BackgroundIt is recommended postoperative adjuvant chemotherapy for all rectal cancers undergoing neo-chemoradiotherapy regardless of the final yield pathology. However, the role of adjuvant chemotherapy in pathological complete response (pCR) remains controversial. We aimed to identify the necessarily of adjuvant chemotherapy in pCR.MethodsConsecutive patients with pCR in Fudan University Shanghai Cancer Center (FUSCC) were enrolled. Meanwhile, a pooled analysis of individual patient with pCR was performed from PubMed and Embase databases for validation.ResultsA total of 171 patients form FUSCC were identified to achieve pCR with up to almost 10 years follow-up. Among them, those receiving adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (log-rank test = 0.17, P = 0.676). The 5y-DFS rates for patients in chemo group and no-chemo group was 87.5 and 88.8%, respectively, showing no significant difference (p = 0.854). No matter chemotherapy regimens, T stage, EMVI and CRM status varied, the results remained consistent. Meantime, the COX model did not demonstrate adjuvant chemotherapy as the independent risk factor for OS and DFS. Additionally, among 18 systemic recurrences in all, the rate of relapse surged rapidly on the 12 months and rose up to peak in the 36th months. In order to validate these results, nine controlled trials involving 5491 patients with pCR were included in this pooled-analysis. For both 5-year overall survival and disease-free survival, the pooling data did not produce a statistically significant effect in cases of adjuvant chemotherapy performed (RR = 0.79 and RR = 0.95, respectively, all p > 0.05).ConclusionThis study suggested that rectal cancer patients with pCR did not benefit from adjuvant chemotherapy and we recommended that achievement of pCR require more prolonged close follow care in case of distant metastasis.

Apolipoprotein C1 (APOC1) promotes tumor progression via MAPK signaling pathways in colorectal cancer.

Aim: Identifying high-efficiency prognostic markers for colorectal cancer (CRC) is necessary for clinical practice. Increasing evidence demonstrates that apolipoprotein C1 (APOC1) promotes carcinogenesis in some human cancers. However, the expression status and biological function of APOC1 in CRC remain unclear.Materials and methods: We detected the association between APOC1 expression and clinicopathological features in 140 CRC patients by immunohistochemistry. Small interfering RNA (siRNA) technology was used to downregulate APOC1 expression in CRC cells. Cell proliferation was estimated by CCK8 and clonogenic assays. The cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were examined by a transwell assay. Gene set enrichment analysis (GSEA) and protein expression of signaling pathways were used to suggest the possible APOC1-associated pathways in CRC.Results: APOC1 was highly expressed in CRC tissues. High immunohistochemistry (IHC) expression of APOC1 was correlated with the N stage, M stage and TNM stage. High IHC APOC1 expression in CRC tissues was associated with poor prognosis. Univariate and multivariate Cox regression analyses showed that APOC1 was an independent risk factor for OS. Cell proliferation of CRC cell lines was inhibited by the downregulation of APOC1. Moreover, si-APOC1 transfection induced cell cycle arrest but low apoptosis increases by regulating the expression of related proteins. Cell migration and invasion were also inhibited by the downregulation of APOC1. The Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA COAD-READ) dataset analyzed by GSEA showed that APOC1 might be involved in the mitogen-activated protein kinase (MAPK) signaling pathway, which was further preliminarily confirmed by Western blotting.Conclusion: APOC1 was overexpressed in CRC tissues, and a high level of APOC1 contributed to a poor prognosis. APOC1 expression influenced the cell proliferation ability and motility capacity of CRC via the MAPK pathway. APOC1 could act as a novel prognostic biomarker in CRC.