Purpose To describe the clinical characteristics and outcomes of patients with dual-phenotype hepatocellular carcinoma (DPHCC) and investigate the use of radiomics to establish an image-based signature for preoperative differential diagnosis. Methods This study included 50 patients with a postoperative pathological diagnosis of DPHCC (observation group) and 50 patients with CK7- and CK19-negative HCC (control group) who attended our hospital between January 2015 and December 2018. All patients underwent Gd-EOB-DTPA-enhanced MRI within 1 month before surgery. Arterial phase (AP), portal venous phase (PVP), delayed phase (DP) and hepatobiliary phase (HBP) images were transferred into a radiomics platform. Volumes of interest covered the whole tumor. The dimensionality of the radiomics features were reduced using LASSO. Four classifiers, including multi-layer perceptron (MLP), support vector machines (SVM), logistic regression (LR) and K-nearest neighbor (KNN) were used to distinguish DPHCC from CK7- and CK19-negative HCC. Kaplan-Meier survival analysis was used to assess 1-year disease-free survival (DFS) and overall survival (OS) in the observation and control groups. Results The best preoperative diagnostic power for DPHCC will likely be derived from a combination of different phases and classifiers. The sensitivity, specificity and accuracy of LR in PVP (0.740, 0.780, 0.766), DP (0.893, 0.700, 0.798), HBP (0.800, 0.720, 0.756) and MLP in PVP (0.880, 0.720, 0.798) were better performance. The 1-year DFS and OS of the patients in the observation group were 69% and 78%, respectively. The 1-year DFS and OS of the patients in the control group were 83% and 85%, respectively. Kaplan-Meier survival analysis showed no statistical difference in DFS and OS between groups (P = 0.231 and 0.326), but DFS and OS were numerically lower in patients with DPHCC. Conclusion The radiomics features extracted from Gd-EOB-DTPA-enhanced MR images can be used to diagnose preoperative DPHCC. DPHCC is more likely to recur and cause death than HCC, suggesting that active postoperative management of patients with DPHCC is required.
Dr. Tarek Haykal et al. (145:1795-1809, 2019) reported a meta-analysis of aspirin for the primary prevention of cancer in individuals without known cancer. The authors found that aspirin use was not associated with significant reduction in cancer mortality or incidence, but with higher rates of bleeding. The findings of this study added some evidence to the clinical practice. However, several issues might have compromised the strength of the evidence of this systematic review. If the investigators could have further clarified the inclusion and exclusion criteria, included all eligible studies, extracted data more meticulously, and performed more necessary sensitivity analyses to confirm the robustness of their findings, the strength of evidence of this meta-analysis would have been stronger.
Background The purpose of this study was to explore the demographics, multimodality therapeutic outcomes*** and prognostic factors in sinonasal rhabdomyosarcoma (SNRMS). Methods We conducted a retrospective analysis of 40 patients who underwent treatment of SNRMS from March 2007 to March 2018. The Kaplan-Meier method and the log-rank test were used to assess survival rates. The Cox regression model was used for multivariate survival analysis. Results In total, 25 males and 15 females were included in the study; the median age was 33 years (range, 2-67 years). All patients underwent surgical resection, and surgery prior to or after adjuvant therapy (chemotherapy and radiotherapy) was performed in 91.4% of the patients. The overall 1-, 3- and 5-year survival rates were 77.0%, 46.5% and 46.5%, respectively, during a mean follow-up time of 27.9 (range, 2-128) months in all patients. The log-rank test showed Intergroup Rhabdomyosarcoma Study (IRS) group and infiltration of the skull base influenced overall survival (p = 0.001; p = 0.022). Advanced IRS stage, lymph node metastasis and tumor size >= 5 cm were also associated with an unfavorable outcome on overall survival (p = 0.01; p = 0.035; p = 0.02). The results of multivariate regression analysis showed patients with IRS group I were associated with better prognosis outcome on overall survival. Conclusion Patients with SNRMS have poor 5-year overall survival, and IRS group is the independent prognostic factor for overall survival.
Purpose N2 lymph-node metastases occur in approximately 6-17% of the patients with T1-2 non-small cell lung cancer (NSCLC). However, the clinical characteristics of N2 patients are not fully understood. Methods This retrospective, multi-center analysis included T1 NSCLC patients receiving surgical resection during a period from Jan 2nd, 2014 to Dec 27th, 2017. The diagnosis was pathologically verified in all cases. Univariate and multivariate logistic regression analyses were conducted to analyze the factors that are associated with pN2 lymph-node metastases. Results A total of 10,885 patients (48.4% men; 84.7% adenocarcinoma) were included in the analysis. The mean age was 59.0 +/- 9.9 years. The mean tumor size was 1.8 +/- 0.8 cm. Of the patients, 3260 (29.9%) were smokers or ex-smokers. Lymph-node metastases were verified in 1808 (16.6%) patients, and 1167 (10.7%) patients had N2 lymph-node metastases. The multivariate analyses indicated that larger tumor size, lower differentiation, CEA level >= 5 ng/mL, vascular invasion (+), and pleural involvement (+) were associated with higher percentages of N2 lymph-node metastases (p < 0.001 for all). Conclusions This study demonstrated the significant association between N2 lymph-node metastases and tumor size and differentiation, CEA levels, and status of vascular invasion and pleural involvement.
Background During the development of tumors, tumors "educate" platelets causing changes in their mRNAs expression profiles and phenotypes, thereby, tumor-educated platelet (TEP) mRNA profile has the potential to diagnose lung cancer. The current study aimed to examine whether TEPs might be a potential biomarker for lung cancer diagnostics. Methods Platelet precipitation was obtained by low-speed centrifugation and subjected to Trizol for total RNA extraction. Platelet MAX, MTURN, and HLA-B mRNA were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors. Results Our results showed that a three-platelet mRNA set: MAX, MTURN, and HLA-B was significantly up-regulated in lung cancer patients as well as in early-stage lung cancer patients compared with those from healthy donors, the area under the curve (AUC) was 0.734, 0.787, respectively, among which platelet MTURN mRNA processed a dramatically high diagnostic efficiency in female patients with lung cancer, its AUC for female was 0.825. More importantly, the three-platelet mRNA set: MAX, MTURN, and HLA-B was associated with chemotherapeutic effect, low mRNA expression of this three-platelet set was correlated with "favorable" first chemotherapy response. Conclusions A three-platelet mRNA set: MAX, MTURN and HLA-B enables blood-based lung cancer diagnosis and chemotherapy response prediction.
Background It is known that there are insufficient prognostic factors for non-small cell lung cancer (NSCLC). It was reported that PD-L1 was a prognostic factor for NSCLC,and c-Myc regulated the expression of PD-L1. Herein, we investigated c-Myc and PD-L1 expression and their association with overall survival (OS) in NSCLC. Methods Formalin-fixed paraffin-embedded specimens were obtained from 128 patients with surgically resected primary NSCLC. Immunohistochemistry was used to assess the expression of PD-L1 and c-Myc in this study. Pearson's Chi squared test or Fisher's exact test was used to analyze the correlation of the expression of PD-L1 and c-Myc with clinicopathologic features. The relationship between OS and the expression of PD-L1 and c-Myc was evaluated by the Kaplan-Meier method and Cox proportional hazards model, respectively. Results Positive expression of PD-L1 was detected in 59 patients (46.1%). Patients with negative expression of PD-L1 had remarkably longer OS than those with positive expression of PD-L1. The positive expression rate of c-Myc in NSCLC accounted for 58.6% (75/128) and its expression was significantly more frequent in males (p = 0.002) and patients with lymph node metastasis (p = 0.029). PD-L1 expression was positively correlated with c-Myc expression (r = 0.459, p < 0.001). The PD-L1 and c-Myc double-positive group had a worse prognosis than other subgroups (p < 0.05), and the PD-L1 and c-Myc double-negative group had a better OS than other subgroups (p < 0.05). Conclusion Conjoint analysis of the expression of PD-L1 and c-Myc was a better prognostic approach for NSCLC patients.
Purpose To compare the clinical results and functional outcomes between two-dimensional conventional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC) with skull-base invasion. Methods A total of 1258 patients were subclassified into two groups: mild skull-base invasion group (792; 63%) and severe skull-base invasion group (466; 37%). Patients were pair matched (1:1 ratio) using six clinical factors into 2DRT or IMRT groups. The Kaplan-Meier method and Cox regression model were performed to assess overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Toxicities were evaluated. Results IMRT significantly improved four-year OS compared with 2DRT (65.6% vs. 81.8%, P = 0.000), DFS (57.3% vs. 73.3%, P = 0.000) and LRRFS (76.5% vs. 87.5%, P = 0.003) in NPC with severe skull-base invasion, but similar results were observed in patients with mild skull-base invasion (P > 0.05). In patients with severe invasion, radiation therapy techniques were found to be an independent prognostic factor for OS (HR = 0.457, P = 0.000), DFS (HR = 0.547, P = 0.000) and LRRFS (HR = 0.503, P = 0.004). IMRT was associated with better OS. In subgroups analysis, IMRT group also had a better survival in OS, DFS (P < 0.05 for all rates) for patients received concurrent chemotherapy and sequential chemotherapy compared to 2DRT in the severe invasion group. The IMRT group displayed lower incidence of mucositis, xerostomia, trismus (< 1 cm) and temporal lobe necrosis than the 2DRT group. Conclusions IMRT significantly improved patient survival compared with 2DRT in NPC patients with severe skull-base invasion, but a similar survival rate was noted in mild invasion patients. Chemotherapy can improve survival in NPC patients with severe invasion. Among the two therapies, IMRT significantly decreased therapy-related toxicity.
Purpose Partial nephrectomy has been persuaded as a widely accepted surgical procedure for T1a (<= 4 cm) renal tumors. However, when treating T1b (4-7 cm) renal cell carcinoma (RCC), the "optimal" method of surgery is still debatable. The aim of the research is to evaluate the long-term oncological and renal functional outcomes of laparoscopic radical nephrectomy (LRN) versus laparoscopic partial nephrectomy (LPN) for patients with T1b RCC. Materials and methods From March 1, 2003 to July 1, 2016, 331 patients were included in the current study. Patients presented with unilateral T1b RCC and underwent either LPN (n = 177) or LRN (n = 154). Relevant clinical data including follow-ups were acquired from patients. Results The operation time of the LPN group patients was longer than that of LRN group (94.3 min vs 88.3 min, p = 0.021) and LPN group patients required shorter stays in hospital (11.5 days vs. 13.4 days, p = 0.009). Contrast to LRN, level of eGFR was superior in LPN at the postoperative time of 1 day, 3 months, 6 months, 12 months and 24 months (all p < 0.001). Kaplan-Meier plots and log-rank tests showed that patients undergoing LPN had a much higher overall survival (OS) (p = 0.007), cancer-specific survival (CSS) (p = 0.006) and metastasis-free survival (MFS) (p = 0.008) than those receiving LRN. In comparison with the LRN group, multivariable Cox analysis indicated that patients of the LPN group had a 1.9-fold OS, 2.9-fold CSS and 2.3-fold MFS. Conclusions For patients with T1b RCC, our findings revealed that OS, CSS and MFS are superior in patients receiving LPN than those treated with LRN. With the benefit of preserving renal function of LPN, which leads a less incidence risk of other systematic diseases, LPN may be the preferred option when condition permits for cases involving T1b RCC.
PurposePulmonary enteric adenocarcinoma (PEAC), defined as tumors with an enteric component exceeding 50% and a histological morphology similar to colorectal cancer (CRC) and metastatic colorectal carcinoma (MCC), is an extremely rare primary lung adenocarcinoma, which was recently recognized by World Health Organization (WHO). Adenocarcinomas with intestinal differentiation have also been described in other anatomic sites, including paranasal sinuses, extrahepatic biliary tree, uterine and cervix, ovary. The morphologic spectrum and immunohistochemical profiles of PEAC overlap with those of colonic adenocarcinomas, the diagnosis of PEAC remains challenging. Currently, colonoscopy has to be performed to confirm the diagnosis, resulting in low compliance due to its invasiveness. Due to the rareness of PEAC, its molecular signature has not been comprehensively examined.MethodsIn this study, we investigated the molecular signatures associated with PEAC and its histological counterparts, CRC and MCC using capture-based targeted sequencing.ResultsWe revealed that 12/13 (92.31%) PEAC patients harbored mutations in well-established driver genes for non-small cell lung cancer and none of them had mutations unique to CRC. Furthermore, 13/15 (86.7%) of MCC harbored mutations that are frequently seen in CRC.ConclusionCollectively, our study showed that PEAC, exhibiting a similar mutational profile with NSCLC, showed a distinctive signature from CRC and MCC. Furthermore, we derived a classification model, intergrading both IHC markers and genetic signature, to accurately diagnose PEAC.
PurposeTo evaluate the efficacy of maintenance apatinib after chemotherapy for extensive-stage (ED) small-cell lung cancer (SCLC).Patients and methodsThis was a retrospective analysis of 23 cases of extensive-stage SCLC admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December 2017. The patients without progression after induction chemotherapy received apatinib 250mg per day until disease progression or unacceptable toxicity occurred. We analyzed the median progression-free survival (PFS), median overall survival (OS) and safety.ResultsOf 23 enrolled patients, 1 was lost to follow-up. The median PFS from the time of maintenance therapy was 4.1months (95% CI 3.63-4.57months). The median PFS from the time of induction chemotherapy was 8.3 months (95% CI 7.20-9.40months). The median OS from the time of maintenance therapy was 12.5months (95% CI 5.51-19.49months). The median OS from the time of induction chemotherapy was 17.0 months (95% CI 9.86-24.14months). The most frequent treatment-related adverse events were hand-foot syndrome (43.5%, 10/23) and secondary hypertension (30.4%, 7/23), followed by fatigue, proteinuria, nausea, and oral mucositis (17.4%, 13.0%, 13.0%, and 8.7%, respectively). Hematologic toxicity included thrombocytopenia (30.4%), leucopenia (26.1%), and anemia (17.4%). The main grade 3 or 4 toxicities were hand-foot syndrome (8.7%, 2/23) and hypertension (4.3%, 1/23).ConclusionMaintenance apatinib was safe and achieved encouraging PFS and OS in extensive-stage SCLC.
PurposeThis study was to compare DA-EPOCH-R and R-CHOP regimen as first-line therapy in diffuse large B cell lymphoma (DLBCL) patients, retrospectively.MethodsA total of 252 cases treated with R-CHOP and 146 cases who received DA-EPOCH-R were enrolled into this study.ResultsOverall, 162 (64.3%) and 105 patients (71.9%) achieved complete remission, 43 (17.1%) and 14 patients (9.6%) achieved partial remission following R-CHOP and DA-EPOCH-R regimen, respectively. After a median follow-up of 48months, better progression-free survival (PFS) was seen in DA-EPOCH-R group, but no better overall survival (OS) was found in patients treated with DA-EPOCH-R compared to R-CHOP (P=0.015 for PFS, P=0.19 for OS). However, subgroup analysis according to cell of origin, international prognostic index (IPI), and age showed DA-EPOCH-R resulted in significantly better PFS and OS than R-CHOP regimen in patients with germinal center B-cell-like (GCB) phenotype (P=0.002 for PFS, P=0.007 for OS), high IPI (P=0.002 for PFS; P=0.03 for OS), and with a younger age (P=0.002 for PFS, P=0.045 for OS). We also compared two regimens in patients with double expressor lymphoma (DEL). The prognosis of DEL patients was significantly worse than non-DEL patients (P<0.001 for PFS, P<0.001 for OS), but DA-EPOCH-R regimen may not overcome the poor prognosis (P=0.47 for PFS, P=0.79 for OS).ConclusionGCB DLBCL, younger patients, and high-risk patients, but not DEL patients, may benefit from continuous-infusion DA-EPOCH-R regimen.
PurposeA thymoma is a tumor arising from the epithelium of the thymus, mostly occurring in the anterior mediastinum. The incidence of this disease is low and research progress in this field is slow. Consequently, there is an urgent need to investigate the correlation between molecular regulation and the prediction of survival and prognosis in patients with thymoma.MethodsWe collected thymoma datasets from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of TCGA datasets were then determined using R software. A gene signature was obtained by screening prognostic DEGs from the TCGA datasets using univariate and multivariate Cox survival analysis. The summation of the weighted expression levels was calculated as a risk score, which could then be used to predict the survival rate and prognosis of patients with thymoma. The validity of this model was verified by the analysis of receiver operating characteristic (ROC) curves and area under the curve (AUC).ResultsIn total, 297 DEGs were identified from the integrated results of TCGA datasets. A seven-gene signature, along with a regression model of prognostic risk, was obtained by Cox survival analysis. The expression levels of the seven genes were then weighted and summed to calculate the risk score for each sample. Patients were effectively divided into high- and low-risk groups using the median risk score (P<0.05). ROC analysis showed that this Cox regression model was effective in predicting the prognosis of patients with thymus tumors (AUC=0.983, P<0.05).ConclusionFor the first time, we identified an effective seven-gene signature in patients with thymic tumors. In the future, the risk and prognosis of patients can be preliminarily assessed using this model, although further testing is required to improve rigor.
BackgroundEmerging evidences show that G-protein-coupled estrogen receptor (GPER) can regulate the progression of various cancers, while its roles in the progression of osteosarcoma (OS) are not well illustrated.MethodsThe expression of GPER in OS cells and tissues were checked. Its roles in cell migration and expression of Snail was checked by use of its agonist G-1.ResultsWe found that the expression of GPER in OS cells and tissues were lower than that in their corresponding controls. OS patients with higher levels of GPER showed increased overall survival rate (OS) as compared with the lower ones. The activator of GPER (G-1) or overexpression of GPER can inhibit the migration and invasion of OS cells and downregulate mesenchymal markers. G-1 can rapidly decrease the expression of Snail, one powerful epithelial-mesenchymal transition transcription factor (EMT-TF). Overexpression of Snail can attenuate the suppression effects of G-1 on migration of OS cells, suggesting that Snail was involved in GPER-regulated migration of OS cells. Mechanically, G-1 rapidly decreased the protein of Snail but had no effect on its mRNA expression. This was because G-1 can decrease the protein stability of Snail. Further, G-1 increased the expression of FBXL5, which can trigger the proteasome-mediated degradation of Snail. Knockdown of FBXL5 can reverse G-1-induced downregulation of Snail in OS cells.ConclusionActivation of GPER can suppress the migration and invasion of OS cells via FBXL5-mediated post-translational down regulation of Snail. It suggested that targeted activation of GPER might be a potent potential therapy approach to overcome the metastasis of OS patients.
PurposeAs an important glycosyltransferase, fucosyltransferase IV (FUT4) is abnormally upregulated in different types of cancers, but its clinical role remains inexplicit. This work aimed to determine the predictive ability of FUT4 in lung adenocarcinoma (LUAD) after curative resection, as well as to explore the role of a possible FUT4 molecular mechanism on LUAD malignant behavior.MethodsA total of 273 LUAD patients after curative resection with complete clinicopathological and RNAseq data from The Cancer Genome Atlas (TCGA) cohort were collected. Correlation of FUT4 with overall survival (OS) was analyzed based on TCGA and further validated by online Kaplan-Meier Plotter database and IHC in 70 LUAD patients recruited in the First Hospital of China Medical University cohort. Multivariate Cox regression analysis and 1000 bootstrapping were performed to verify the predictive value of FUT4. Gene set enrichment assay (GSEA) was performed to investigate the biological characteristics. Correlation between PD-1 and FUT4 was analyzed based on TCGA cohort and validated by IHC on cohort from our hospital.ResultsIncreased FUT4 expression led to reduced overall survival (OS) of LUAD patients based on TCGA (p=0.006 and 0.001 for dichotomous and trichotomous modeling, respectively) and externally validated in KMPLOTTER (p=0.01) and by IHC based on cohort from our hospital (p=0.005 and p=0.019 for dichotomous and trichotomous modeling, respectively). FUT4 overexpression was an independent high risk factor for OSalong with advancedpT stage and pTNM stage (p=0.001, p=0.037, and p<0.001, respectively). GSEA revealed that FUT4 overexpression might correlate with shortened survival of LUAD patients by promoting cell proliferation via ERBB signaling, and suppressing immune response-related pathways. FUT4 expression positively correlated with PD-1 in TCGA (p=0.026) and validated by IHC on cohort from our hospital (p=0.029).ConclusionsIncreased FUT4 expression led to reduced OS in operable LUAD. FUT4 showed significant correlation with immune response and PD-1 expression.
PurposeNon-coding RNAs (ncRNAs) have been a hot topic for many years in the field of cancer research,especially miRNAs and lncRNAs. Because they play critical roles in regulating various cellular processes and are more often involved in tumorigenesis than protein-coding genes. But the cross talk between miRNAs and lncRNAs in cancer has been scarcely studied. This articleaims to provide a retrospective review of the latest research on the link between miRNAs and lncRNAs in lung cancer and discusses their potential role as diagnostic biomarkers and therapeutic targets for lung cancer in clinical practice.MethodsWe reviewed literatures about ncRNAs and lung cancer from PUBMED databases in this article.ResultsAs shown in our review, miRNAs and lncRNAs could represent underlying targets for diagnosis, therapy, prognosis, and drug resistence of lung cancer. By acting as ceRNAs, lncRNAs can competitively inhibit the expression levels of miRNAs, and the lncRNA/miRNA axis can contribute to tumorigenesis, metastasis, and mutidrug resistance in lung cancer via various classic signaling pathways or related proteins.ConclusionBased on present knowledge, ncRNAs may provide a novel perspectiveto understand the pathogenesis of lung cancer and could be candidates in screening of therapeutic targets for lung cancer.