Postoperative Overall Survival Of Patients Research Articles

Upregulation of a novel LncRNA AC104958.2 stabilized by PCBP2 promotes proliferation and microvascular invasion in hepatocellular carcinoma

Long non-coding RNAs (lncRNAs) were reported to be involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Microvascular invasion (MVI) is an independent predictor for early recurrence and overall survival in postoperative patients with HCC. However, the mechanisms how lncRNAs affect HCC and MVI remain elusive. By RNA sequencing (RNA-seq) in a series of 65 HCC samples and 30 paired adjacent non-tumor liver tissue, we identified a novel lncRNA AC104958.2 that was significantly upregulated in HCC tissues and associated with MVI. Overexpression of AC104958.2 obviously elevated cell viability, metastasis, invasion and epithelial-mesenchymal transition (EMT), while knockout of AC104958.2 mediated by CRISPR/Cas9 technique showed the opposite effects. In addition, the interaction between AC104958.2 and Poly (rC) binding protein 2 (PCBP2) was identified by RNA pull down and mass spectrometry (MS), which was further validated by RNA immunoprecipitation (RIP). PCBP2 was also upregulated in HCC and associated with MVI. High expression of both AC104958.2 and PCBP2 was correlated with tumor size, TNM stage and MVI in HCC. Overexpression of PCBP2 greatly increased the cell viability, metastasis, invasion and EMT. Moreover, actinomycin D assay showed that overexpression of PCBP2 enhanced the RNA stability of AC104958.2. In conclusion, our study showed that a novel lncRNA AC104958.2 exerted oncogenic roles in HCC and might be a promising biomarker and therapeutic target.

Preoperative serum fibrinogen as a valuable predictor in the nomogram predicting overall survival of postoperative patients with gallbladder cancer.

Coagulation and fibrinolysis activation are frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis and worse long-term outcome. The specific aim of this study was to develop an effective prognostic nomogram to help make individualized estimates for patients with resected gallbladder cancer (GBC). Patients with resected GBC who were diagnosed between 2006 and 2014 at Xinhua Hospital were selected. Model performance was measured by c-index and calibration curve. The results were further validated using bootstrap and a cohort of 38 patients from a branch hospital who underwent surgery from 2006 to 2014. Backward stepwise selection and Lasso were applied respectively to select predictors. T stage, N stage, and preoperative serum fibrinogen were included in the final model. Predictions correlated well with observed 1- and 3-year survival. The c-index for predicting survival was 0.74 (95% confidence interval, 0.70-0.78), which was statistically higher than that of the AJCC 7th system and Nevin system (P=0.04, 0.04, respectively). In the validation cohort, the nomogram performed better than the other two staging systems (c-index: 0.71 vs. 0.67 and 0.67). The validated nomogram is a practical tool for predicting the overall survival (OS) of postoperative GBC patients. Preoperative serum fibrinogen levels were associated with tumor progression and may be an independent predictor for GBC patients.

Correlation of Prognostic Nutritional Index with Overall Survival of Postoperative Patients with Thymoma

Correlation of Prognostic Nutritional Index with Overall Survival of Postoperative Patients with Thymoma

Impact of examined lymph node count on staging and long-term survival of patients with node-negative stage III gastric cancer: a retrospective study using a Chinese multi-institutional registry with Surveillance, Epidemiology, and End Results (SEER) data validation.

BackgroundAccumulating evidence has confirmed the potential prognostic value of examined lymph nodes (ELNs) in patients with gastric cancer (GC). However, there is currently no consensus on the threshold ELN number for predicting both stage migration and long-term survival, especially in patients with stage III GC. This study aimed to validate the need to increase the ELN count to improve its prognostic accuracy in node-negative patients with stage III GC after curative gastrectomy.MethodsThis retrospective, population-based study analyzed the clinical data of 84 patients with node-negative stage III GC from three high-volume institutions in China and 196 cases from the Surveillance, Epidemiology and End Results (SEER) program registry. The optimal number of ELNs was determined by receiver operating characteristic (ROC) curve analysis. Clinicopathological characteristics significantly related to survival were evaluated using the Kaplan-Meier method and Cox proportional hazards analysis. Stratified analyses were adopted to assess the prognostic predictive ability of the identified optimal number of ELNs in different populations. Survival differences among subgroups were analyzed to assess the impact of ELN count on stage migration according to overall survival (OS) among GC patients.ResultsThe optimal number of ELNs was >31 according to ROC analysis of patients with node-negative stage III GC who underwent gastrectomy. Multivariate analysis identified ELNs as an independent predictor of postoperative OS in patients with node-negative stage III GC in both the Chinese cohort [hazard ratio (HR) 0.235; P<0.001] and the SEER cohort (HR 0.421; P<0.010). Stratified analysis demonstrated that >31 ELNs was a prerequisite for accurate prognostic evaluation of patients with node-negative stage III GC, regardless of sex, tumor size, and other factors. Stage migration between pT4bN0M0 and pT4bN1M0 was detected in patients with >31 ELNs. A nomogram was created to predict OS among patients with node-negative stage III GC. These results were validated using data from the SEER cohort.ConclusionsThe number of ELNs was significantly associated with prognosis in patients with stage III GC after gastrectomy with systemic lymphadenectomy in both the Chinese and SEER cohorts. The results suggest that >31 ELNs are required for an accurate prognostic evaluation in patients with GC, especially those with node-negative stage III GC.

Breast cancer spinal metastases: Prognostic factors affecting survival after surgery. A retrospective study

Breast cancer spinal metastases (BCSM) are common and require proper treatment that leads to an improvement of the quality of life and contributes to the quod vitam prognosis. Surgical treatment is often required for intractable pain, spinal cord compression or spinal instability.The aim of this retrospective study is to identify which prognostic factors could affect postoperative overall survival in patients affected by BCSM.We report a retrospective cohort study of patients with BCSM, surgically treated from September 2009 to May 2018. Demographic and clinical data were collected. Kaplan-Meier method was used to estimate overall survival, and the log-rank test was used to compare survival curves.A total of 77 patients were studied. The median age at the time of surgery was 54 years. The median follow-up was 49 months. The 3-year and 5-year overall survival rates were 61% (95%CI: 47.5–72.1) and 43.3% (95%CI: 28.8–57.1). Metastatic bone disease (p = 0.0196), preoperative neurological impairment (p = 0.0029), Karnofsky status <70 (p = 0.0241) reduce survival. With multivariate analysis, the effect of Karnofsky score loses statistical significance.The presence of concurrent bone metastases and a preoperative neurological deficit are independent prognostic factors. Therapeutic choices are based on a multidisciplinary assessment that takes into consideration several factors, including an accurate study of prognostic factors.

Prognostic significance of low expression of B-cell translocation gene 1 (BTG 1) in skin squamous cell carcinoma

Although the B-cell translocation gene 1 (BTG1) plays an important role in apoptosis and negatively regulates cell proliferation, BTG1 expression in skin squamous cell carcinoma (SCC) has not been reported. In this study, we wanted to investigate the significance of BTG1 expression in SCC and adjacent tissues. The expression of BTG1 protein and mRNA in SCC tissues and adjacent tissues were detected by immunohistochemistry technique (IHC), Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). IHC staining showed that the positive expression rate of BTG1 protein in SCC tissues was 54.00%; and the positive rate was 90.50% in the adjacent tissues. Western blot showed that the expression of BTG1 protein in SCC tissues was significantly lower than that in the adjacent tissues (P less than 0.05). RT-PCR showed that the positive rate of BTG1 mRNA in SCC was 50.50%, which was significantly lower than that in adjacent tissues 89.00% (P less than 0.05). Both BTG1 mRNA and protein expression are related to tumor diameter, stage, tumor metastasis and the degree of tumor differentiation in SCC. Patients exhibiting lower BTG1 protein expression in the SCC tissues had a significantly shorter disease-specific survival rate. BTG1 protein expression, tumor diameter, tumors site and stage were independent factors affecting the overall survival of postoperative patients. Further, BTG1 overexpression inhibited A431 cell proliferation ability, while BTG silencing enhanced A431 cell proliferation ability. The lower expression of BTG1 in SCC may be associated with the occurrence, development and prognosis of SCC.

Clinical significance of high expression of proliferating cell nuclear antigen in non-small cell lung cancer.

Although proliferating cell nuclear antigen (PCNA) plays an important role in tumor proliferation and its expression level is closely related to the biological activity of tumor cells, PCNA expression in non-small cell lung cancer (NSCLC) has been seldom reported. In this study, we aimed to investigate the significance of PCNA expression in NSCLC tissues. PCNA expression in NSCLC and adjacent tissues were assessed by immunohistochemistry (IHC), western blotting, and reverse transcription polymerase chain reaction. Single factor analysis was used to study the relationship between the expression of PCNA and clinicopathological features of NSCLC. Multi-factor Cox survival analysis was used to evaluate the relationship between the expression of PCNA and overall survival of postoperative NSCLC patients. The areas under the receiver operating characteristics were calculated to evaluate the value of PCNA expression level in predicting the 3-year survival of NSCLC patients. IHC analysis showed that the positive expression rates of PCNA protein in NSCLC and adjacent tissues were 91.79% (257/280) and 25.83% (31/120), respectively. Western blotting confirmed that PCNA protein level was significantly higher in NSCLC tissues than in the adjacent tissues (P < .05). Reverse transcription polymerase chain reaction showed that the positive rate of PCNA mRNA in NSCLC was 88.93% (249/280), which was significantly higher than that in adjacent tissues 29.17% (35/120) (P < .05). Both PCNA mRNA and protein levels were correlated with tumor differentiation, size, metastasis, and stage in NSCLC. Patients exhibiting higher PCNA protein expression had a significantly shorter disease-specific survival rate than the other patients. PCNA protein level and tumor pathological type, metastasis, differentiation degree, and stage were independent factors affecting the overall survival of postoperative patients. The areas under the receiver operating characteristics of PCNA mRNA for predicting the 3-year survival of NSCLC patients was 0.89 (0.79–0.98), with a sensitivity and specificity of 0.84 and 0.76, respectively. In conclusion, high PCNA protein and mRNA levels may be associated with the occurrence, development, and prognosis of NSCLC.

The role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 in esophageal squamous cell carcinoma.

6-phosphofructo-kinase-2/fructose diphosphatase-2 isoenzyme 3 (PFKFB3) is closely related to the growth of many types of cancer cells. Glycolysis not only provides Adenosine triphosphate for the growth of tumor cells, but also protects them from acid products, which is beneficial to the invasion and metastasis of tumors. However, PFKFB3 expression in esophageal squamous cell carcinoma (ESCC) has been scarcely reported. In this study, the role of PFKFB3 was studied in 120 ESCC samples using immunohistochemistry technique (IHC), western blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR). Both PFKFB3 protein and gene expression in ESCC tissues were significantly higher than in adjacent non-tumor tissues (P < .05). Single factor analysis showed that both PFKFB3 protein and gene expression are related to infiltration depth, stage, tumor metastasis, and the degree of tumor differentiation in ESCC. Multifactor Cox survival analysis revealed that PFKFB3 protein expression, tumor location, tumor metastasis, tumor differentiation degree, and tumor stage were independent factors affecting the overall survival of postoperative patients. Multivariate Cox survival analysis showed that PFKFB3 mRNA has a good performance for predicting 3-year survival of patients with ESCC 0.89 (0.79–0.99), with a sensitivity of 0.85 and specificity of 0.77. Encouragingly, the sensitivity and specificity of PFKFB3 in the diagnosis of early ESCC (stage I and stage II) can reach 87.8% and 91.5%. In conclusion, high PFKFB3 protein and gene expression may be associated with the occurrence, development, and prognosis of ESCC. PFKFB3 could be used to help develop new therapeutic and diagnostic strategies for ESCC patients.

EGFR inhibitors as adjuvant therapy for resected non-small cell lung cancer harboring EGFR mutations

ObjectivesCisplatin-based chemotherapy as an adjuvant therapy for resected non-small cell lung cancer (NSCLC) has reached its plateau, and it is limited by a high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected NSCLC harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as an adjuvant therapy for targeted patients. Materials and methodsStudies were identified via electronic search. The pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for the meta-analysis. ResultsThere were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. The results showed that adjuvant treatment with EGFR-TKIs can prolong both the OS and DFS when compared to treatment without TKIs as an adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I2 = 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I2 = 37%, P = 0.10). The results of the predefined subgroup analyses in this meta-analysis suggested a greater DFS with the mono EGFR-TKIs compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.30). We also found that treatment with EGFR-TKIs plus chemotherapy was associated with a significantly longer DFS and OS compared to mono chemotherapy in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95% CI, 0.34-0.68; P < 0.0001; heterogeneity I2 = 47%, P = 0.07; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I2 = 57%, P = 0.05). Additionally, less severe adverse events (SAEs) were observed in the TKIs group (OR, 0.22; 95% CI, 0.14 to 0.37, P < 0.00001; heterogeneity I2 = 22%, P = 0.28). ConclusionThe addition of EGFR-TKIs to adjuvant chemotherapy can prolong the OS and PFS for resected NSCLC. Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completely resected patients with EGFR mutation-positive NSCLC. Statement of significanceThe clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. This study demonstrates that EGFR-TKIs as an adjuvant therapy could prolong the DFS and potentially prolong the OS in postoperative patients. Therefore, this therapy paves the way for EGFR-TKIs to be an adjuvant treatment for NSCLC.

Clinical significance of high expression of stanniocalcin-2 in hepatocellular carcinoma

To investigate the significance of stanniocalcin-2 (STC2) expression in hepatocellular carcinoma (HCC) tissues and adjacent tissues. Levels of STC2 in HCC tissue were detected in 200 HCC patients tissues and adjacent tissues as controls by immunohistochemistry technique (IHC) and reverse transcriptase-PCR (RT-PCR). Single factor analysis was used to study the relationship between expression of STC2 mRNA and protein and clinicopathological features of HCC. Multifactor Cox survival analysis was used to relationship between the expression of STC2 and overall survival of postoperative patients with HCC. IHC staining showed that the expression of STC2 protein rate was 81.00% (163/200). And the positive rate of adjacent tissues was 29.00% (58/200). Western blot showed that the expression of STC2 protein in HCC was significantly higher than that in the adjacent tissues (P<0.05). RT-PCR showed that the positive rates of STC2 mRNA expression in HCC were 75.50% (151/200), which was significantly higher than that in adjacent tissues 14.50% (29/200) (P<0.05). Both STC2 mRNA and protein expression are related to tumor diameter, stage, tumor metastasis, carcinoma emboli in the portal vein and the degree of tumor differentiation in HCC. The HCC patients with higher expression of STC2 had shorter median survival time. STC2 expression, tumor diameter, carcinoma emboli in the portal vein, tumor differentiation degree, and tumor stage were independent factors affecting the overall survival of postoperative patients. The high expression of STC2 mRNA and protein expression in HCC may be associated with the occurrence, development, and prognosis of HCC. STC2 may also be possible to help developing new therapeutic strategies for HCC.

Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma.

Cancer-associated fibroblasts (CAFs) are essential constituents of cancer-supportive microenvironments. The high incidence of hepatocellular carcinoma (HCC) in advanced fibrosis patients implies that fibroblasts have a promoting effect on HCC development. We aimed to explore the regulators of phenotypes and function of CAFs in the liver. We established primary cancer-associated fibroblasts (CAFs) and non-cancerous liver fibroblasts (NFs) from 15 patients who underwent HCC resection. We compared phenotypes, capacity of cytokine/chemokine production and gene expression profiles between pairs of CAFs and NFs from the same donors. We examined resected tissue from additional 50 patients with HCC for immunohistochemical analyses. The CAFs expressed more ACTA2 and COL1A1 than the NFs, suggesting that CAFs are more activated phenotype. The CAFs produced larger amounts of IL-6, IL-8 and CCL2 than the NFs, which led to invasiveness of HuH7 in vitro. We found that Bone Morphogenetic Protein-4 (BMP4) is up-regulated in CAFs compared to NFs. The CAF phenotype and function were gained by BMP4 over-expression or recombinant BMP4 given to fibroblasts, all of which decreased with BMP4 knockdown. In tissues obtained from the patients, BMP4-positive cells are mainly observed in encapsulated fibrous lesions and HCC. Positive expression of BMP4 in HCC in resected tissues, not in fibroblasts, was associated with poorer postoperative overall survival in patients with HCC. Endogenous and exogenous BMP4 activate liver fibroblasts to gain capacity of secreting cytokines and enhancing invasiveness of cancer cells in the liver. BMP4 is one of the regulatory factors of CAFs functioning in the microenvironment of HCC.

MicroRNA-325 Is a Potential Biomarker and Tumor Regulator in Human Bladder Cancer.

Purpose:We evaluated whether human microRNA-325 may be a potential biomarker and tumor regulator in bladder cancer.Methods:Human microRNA-325 expression was probed by quantitative real-time polymerase chain reaction in both in vitro bladder cancer cell lines and in vivo bladder carcinoma tissues retrieved from patients with cancer. The prognostic potential of human microRNA-325 in predicting postoperative overall survival of patients with bladder cancer was estimated. Endogenous human microRNA-325 was overexpressed by lentiviral transduction in bladder cancer cell lines, T24 and 5637 cells. The tumor regulatory effects of human microRNA-325 upregulation on T24 and 5637 cells were evaluated both in vitro and in vivo.Results:Human microRNA-325 was aberrantly downregulated in both bladder cell lines and human bladder carcinomas. Lowly expressed human microRNA-325 in bladder carcinoma was closely associated with poor postoperative overall survival of patients with cancer. In T24 and 5637 cells, virally transduced cells had markedly upregulated human microRNA-325 expressions. Biochemical assays demonstrated that human microRNA-325 upregulation in bladder cancer had tumor-suppressive functions by decreasing cancer proliferation, cisplatin chemoresistance, and cancer migration in vitro and hindering transplantation growth in vivo and cell cycle transition.Conclusion:Human microRNA-325 is lowly expressed and may serve as a potential prognostic biomarker in human bladder cancer. After further validation, human microRNA-325 may be a novel therapeutic target for suppressing carcinoma in patients with bladder cancer.

Albumin concentrations plus neutrophil lymphocyte ratios for predicting overall survival after curative resection for gastric cancer.

BackgroundIn patients with gastric cancer (GC), survival is poor, given the late diagnosis. Risk-stratifying these patients earlier could help improve care. We determined whether combining preoperative albumin concentration and the neutrophil lymphocyte ratio (COA-NLR) could predict overall survival (OS) better than other prognostic indexes.MethodsWe calculated the COA-NLR and other prognostic indexes with data obtained within 1 week before surgery in a retrospective analysis of patients with GC undergoing curative resection between September 2000 and November 2012. Patients with concentrations of hypoalbuminemia above 35 g/L and an NLR value of 2.3 or higher were given a score of 2. Patients with one of these conditions or neither were allocated scores of 1 or 0, respectively. Patients were monitored until July 2014.ResultsOS in the 873 eligible patients was 44.9% in patients with a COA-NLR score of 0, 29.8% in patients with a score of 1, and 20.3% in patients with a score of 2 (P<0.001). The COA-NLR score was independently associated with OS (hazard ratio, 1.35; 95% confidence interval, 1.12 to 1.63; P=0.002). Moreover, the area under the receiver operating characteristics curve was 0.62 for the COA-NLR, which was significantly higher (<0.001) than that of the NLR ratio (0.60), the Glasgow prognostic score (0.58), and the platelet lymphocyte ratio (0.54). The COA-NLR was especially accurate for patients with stage I–II GC and the three values (0, 1, and 2) divided patients into subgroups more accurately than did the other indexes (area under the curve value: 0.66, P<0.001).ConclusionThe preoperative COA-NLR index is useful for predicting postoperative OS in patients with GC and can be used to guide targeted therapy.

Analysis of the survival of 123 patients with intrahepatic cholangiocarcinoma after surgical resection

To investigate the prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection. The clinicopathological and follow-up data of 123 patients with intrahepatic cholangiocarcinoma who underwent surgical resection in Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and June 2015 were collected and reviewed, and their survival and prognosis were analyzed with the Kaplan-Meier method and Cox regression model. The median follow-up time was 22 months and median recurrence-free survival time was 8.97 months. The 1-, 2- and 3-year recurrence rates were 58.6%, 68.9% and 76.5%, respectively. Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, extrahepatic invasion, and combination of tumor necrosis were significant adverse prognostic factors affecting the postoperative recurrence-free survival in patients with intrahepatic cholangiocarcinoma after surgical resection (P<0.05 for all). The median overall survival time was 21.17 months, and the 1-, 3- and 5-year overall survival rates were 76.6%, 33.2% and 26.1%, respectively. The Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, and extrahepatic invasion were significant adverse prognostic factors affecting the postoperative overall survival in patients with intrahepatic cholangiocarcinoma after surgical resection(P<0.05 for all). Preoperative rise in CEA, lymph node metastasis, multiple lesions and extrahepatic invasion are significant adverse prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection.