Unfavorable Overall Survival Research Articles

Autologous stem cell transplantation for HIV-associated lymphoma in the antiretroviral and rituximab era: a retrospective study by the EBMT Lymphoma Working Party.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.

Prognostic values of inhibitory κB kinases mRNA expression in human gastric cancer.

Background: Inhibitory κB kinases (IKKs) play a key role in modulating proinflammatory and growth stimulating signals through their regulation of the nuclear factor κB (NF-κB) cascade. Therefore, the level of expression of IKKs represents a viable prognostic predictor with regard to various pathological processes. The prognostic value of IKKs expression in gastric cancer remains unclear. Methods: We used the ‘Kaplan–Meier plotter’ (KM plotter) online database, to explore the predictive prognostic value of individual IKKs members’ mRNA expression to overall survival (OS) in different clinical data including pathological staging, histology, and therapies employed. Results: Our results revealed that a higher mRNA expression of inhibitor of NF-κB kinase subunit α (IKKα) was correlated to better OS, whereas higher mRNA expression of IKKβ, inhibitor of NF-κB kinase subunit γ (IKKγ), inhibitor of NF-κB kinase subunit ε (IKKε), and suppressor of IKKε (SIKE) were generally correlated to unfavorable OS in gastric cancer. Increased mRNA expression of IKKε also showed better outcomes in stage IV gastric cancer. Further a correlation between elevated levels of mRNA expression of both IKKε and SIKE was found to have favorable OS in diffuse type gastric cancer. It was also revealed that high expression of SIKE had favorable OS when treated with other adjuvant therapies, while worse OS when treated only with 5FU therapy. Conclusion: Our results suggest that mRNA expression of individual IKKs and SIKE are associated with unique prognostic significance and may act as valuable prognostic biomarkers and potential targets for future therapeutic interventions in gastric cancer.

Circulating tumor cells as an independent prognostic factor in advanced colorectal cancer: a retrospective study in 121 patients

PurposeThis study aimed to evaluate the prognostic value of circulating tumor cells (CTCs) in advanced colorectal cancer (CRC) patients during chemotherapy course.MethodsFrom January 2016 to September 2017, the clinicopathological variables, such as gender, age, tumor location, tumor de-differentiation, depth of invasion, lymphatic invasion, distant metastasis, TNM stage, CTCs enumeration during 2-6 cycles of chemotherapy, and serum carcinoembryonic antigen (CEA) level during the same period, of 121 newly acquired and histopathologically confirmed CRC patients were collected from the Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine. All patients were followed up for survival until the end of November 2018. Statistical analysis focused on the associations between CTCs counts and clinicopathological variables. Overall survival (OS) and progression-free survival (PFS) among different prognostic factors were calculated using the Kaplan–Meier method, and the differences between the survival curves were compared by using the log-rank test. Factors of prognostic significance were investigated with the multivariate Cox regression analysis.ResultsHere, 71 of 121 patients were CTC-positive, in which CTC-positive rate was positively correlated with the depth of invasion, lymphatic invasion, distant metastasis, TNM stage, and serum CEA level (P < 0.05 for all). However, no significant difference was found between CTC-positive and other clinicopathological variables (P > 0.05 for all), such as gender, age, tumor location, and tumor de-differentiation. CTCs counts gradually increased with the advancement of depth of invasion (P = 0.002), lymphatic invasion (P = 0.004), distant metastasis (P = 0.007), TNM stage (P = 0.001), serum CEA level (P = 0.001), and decreased tumor de-differentiation (P = 0.011). Furthermore, the Kaplan–Meier survival curves showed that patients with CTC-positive had a significantly unfavorable PFS (14 vs. 23 months, P = 0.001) and OS (18 vs. 25 months, P = 0.003). The multivariate Cox regression analyses revealed that the presence of CTCs during chemotherapy was an independent factor for unfavorable PFS (hazard ratio (HR) 2.682, P = 0.017, 95% confidence interval (CI) 1.193–6.029) and OS (HR 2.790, P = 0.048, 95% CI 1.010–7.705) in advanced CRC patients.ConclusionsThis study provided an evidence that the presence of CTCs may be valuable for predicting survival outcome, and CTCs was associated with unfavorable survival in advanced CRC patients during chemotherapy.

O Blood Type Is Associated with Unfavorable Distant-metastasis-free Survival in Female Patients with Nasopharyngeal Carcinoma: A Retrospective Study of 2439 Patients from Epidemic Area.

Purpose: To identify the association between ABO blood type and the survivals in nasopharyngeal carcinoma patients.Patients and methods: We retrospectively analyzed 2439 consecutive non-metastasis nasopharyngeal carcinoma patients between January 2001 and December 2004 at the Sun Yat-sen University Cancer Center. Survival outcomes were compared using Kaplan-Meier method. Univariate and multivariate analysis was performed by Cox regression model. Chi-square test was performed to compare categorical variables.Results: In the whole patients, compared with non-O blood type (A, B, and AB) patients, O blood type patients had significantly lower 5-year distant metastasis-free survival (DMFS) (adjusted hazard ratio (aHR)= 1.268, 95% CI 1.010-1.592, P=0.041). Moreover, we observed in female patients, O blood type patients had significantly lower 5-year overall survival (OS), disease-specific survival (DSS) and DMFS than those with non-O blood type (aHR=1.495, 95% CI 1.032-2.165, P=0.034 for OS; aHR=1.566, 95% CI 1.054-2.328, P=0.026 for DSS; aHR=1.779, 95% CI 1.056-2.998, P=0.030 for DMFS). In male patients, there was no significant difference observed between O blood type patients and non-O blood type patients in any survival endpoints.Conclusion: O blood type was associated with an unfavorable DMFS in female patients with nasopharyngeal carcinoma in epidemic area, which might contribute to unfavorable OS and DSS in female patients, even contribute to a lower DMFS in the whole patients. It might be beneficial to predict metastasis so as to guide the treatment in female patients with nasopharyngeal carcinoma in epidemic area.

The Significance Role of microRNA-200c as a Prognostic Factor in Various Human Solid Malignant Neoplasms: A Meta-Analysis.

Objective: The aim of this study was to conduct a meta-analysis of 49 relevant studies to evaluate the prognostic value of miRNA-200c in various human malignant neoplasms.Methods: All relevant studies were identified by searching PubMed, Embase and Web of Science until August 15st, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of miRNA-200c for overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS) were calculated to investigate such associations.Results: Overall, 49 eligible studies were included in this meta-analysis. Our results showed that high expression of miRNA-200c was significantly correlated with a poor OS in cancer (pooled HR = 1.32, 95% CI: 1.06-1.65), but was not significantly correlated with PFS/RFS/DFS in cancer (pooled HR=1.05, 95% CI: 0.84-1.23). In our subgroup analysis, high miRNA-200c expression predicted a significantly worse OS (pooled HR = 1.50, 95% CI: 1.12-2.01) only in Caucasians. Moreover, high miRNA-200c expression even showed significantly poor OS (pooled HR = 1.88, 95% CI: 1.39-2.54) in blood samples. In addition, a significantly unfavorable OS (pooled HR = 2.69, 95% CI: 1.49-4.85) and (pooled HR = 2.66, 95% CI: 1.07-6.59) associated with up-regulated miRNA-200c expression were observed in breast cancer and endometrial cancer, respectively. Besides, high miRNA-200c expression also showed significantly poor PFS/RFS/DFS (pooled HR=1.66, 95% CI: 1.03-2.67) in breast cancer.Conclusions: Our findings indicated that high miRNA-200c expression was a promising biomarker for patient survival and disease progression in malignant tumors, especially in breast cancer and endometrial cancer. Considering the insufficient evidence, further large-scale researches and clinical studies were needed to verify these results.

Prognostic values of E2F mRNA expression in human gastric cancer.

Gastric cancer (GC) is the second most frequent cause of cancer-related mortality in the world, with Eastern Asia having the highest incidence rates. E2F is a family of transcription factor proteins that has a variety of functions, which include control of cell cycle, cell differentiation, DNA damage response and cell death. E2F transcription factors are divided into two subfamilies: transcription activators (E2F transcription factors 1 (E2F1), 2 (E2F2) and 3a (E2F3a)) and repressors (E2F3b, E2F transcription factors 4 (E2F4), 5 (E2F5), 6 (E2F6), 7 (E2F7) and 8 (E2F8)). Studies have demonstrated that E2F had prognostic significance in a number of cancers. However, the entirety of the prognostic roles of E2F mRNA expression in GC has not yet been apparently determined. In the present study, the prognostic value of individual family members of E2F mRNA expression for overall survival (OS) was evaluated by using online Kaplan–Meier Plotter (KM Plotter) database. Our result demonstrated that high expressions of three family members of E2F (E2F1, E2F3, E2F4) mRNA were significantly associated with unfavourable OS in all GC patients. However, increased expressions of E2F2, E2F5, E2F6 and E2F7 were significantly associated with favourable OS, especially for higher clinical stages in GC patients. These results provided a better insight into the prognostic functions of E2F mRNA genes in GC. Although the results should be further verified in clinical trials, our findings may be a favourable prognostic predictor for the development of newer therapeutic drugs in the treatment of GC.

Integrin Subunit beta 8 (ITGB8) Upregulation Is an Independent Predictor of Unfavorable Survival of High-Grade Serous Ovarian Carcinoma Patients.

Background ITGB8 encodes a β subunit of integrin (integrin β8), which is upregulated in some types of cancer. In the current study, we examined the expression profile of ITGB8 in serous ovarian cancer (SOVC) and investigated its potential as an independent prognostic indicator for overall survival (OS) and recurrence-free survival (RFS) in high-grade SOVC.Material/MethodsA secondary study was conducted based on genomic and survival data in large online databases, including the Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA), and the Cancer Genome Atlas-Ovarian cancer (TCGA-OV). Kaplan-Meier curves were generated to evaluate the association between ITGB8 expression and OS/RFS. Univariate and multivariate analysis were performed with the Cox regression model.ResultsITGB8 was significantly upregulated in ovarian cancer tissues compared to that in normal ovary tissues. High-grade SOVC patients with high ITGB8 expression had significantly shorter OS and RFS compared to their low-expression counterparts. Increased ITGB8 expression might be an independent prognostic indicator of unfavorable OS (HR: 1.424, 95%CI: 1.228–1.653, p<0.001) and RFS (HR: 2.167, 95%CI: 1.507–3.114, p<0.001) in high-grade SOVC. DNA amplification was frequent (149/509, 29.3%) in high-grade SOVC patients and was associated with increased ITGB8 expression compared to the copy-neutral cases.ConclusionsITGB8 expression might be a valuable prognostic biomarker in high-grade SOVC, the expression of which might be regulated by its DNA copy numbers.

Katanin P80 expression correlates with lymph node metastasis and worse overall survival in patients with breast cancer.

The aim of this study was to investigate the correlation of katanin P80 expression with clinicopathological features and overall survival (OS) in surgical breast cancer (BC) patients. Four hundred and fourteen BC patients underwent surgery were analyzed in this retrospective cohort study. Katanin P80 expression was examined by immunofluorescence assay. The median follow-up duration was 118.0months (quantiles: 99.0-140.5months), the last follow-up date was Jul 1st 2017. Eighty-five patients (20.5%) with katanin P80 positive expression and 329patients (79.5%) with katanin P80 negative expression were observed in this research. Katanin P80 positive expression was correlated with higher N stage (p< 0.001) and TNM stage (p< 0.001). K-M curve and log-rank test revealed that katanin P80 positive patients presented with shorter OS compared with katanin P80 negative patients (p< 0.001). Multivariate Cox's regression analysis disclosed that katanin P80 positive expression (p< 0.001) and histologic grade (p< 0.001) could independently predict unfavorable OS. Furthermore, subgroups analysis was performed, which illuminated that katanin P80 positive expression was correlated with shorter OS in all subgroups divided by molecular subtyping and TNM stage (all p< 0.05) except in TNM stage I subgroup (p= 0.573). Katanin P80 expression positively correlated with lymph node metastasis and could abe a novel biomarker for prognosis in BC patients.

Circular RNA ciRS-7 correlates with advance disease and poor prognosis, and its down-regulation inhibits cells proliferation while induces cells apoptosis in non-small cell lung cancer.

This study aimed to assess the association of circular RNA (circRNA) ciRS-7 expression with clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients, and to investigate its effect on cells proliferation as well as apoptosis in NSCLC. 132 patients with primary NSCLC who received surgical resection were recruited in this retrospective study. All patients' tumor tissue and paired adjacent tissue were collected for circRNA ciRS-7 expression detection by RT-qPCR. Disease-free survival (DFS) and overall survival (OS) were calculated. CCK-8 and Annexin-V/propidium iodide (AV/PI) assays were performed to detect cells proliferation and apoptosis in A549 cells after circRNA ciRS-7 inhibition plasmid transfection. CircRNA ciRS-7 expression in tumor tissue was elevated compared to paired adjacent tissue, and positively correlated with tumor size, lymph node metastasis and tumor node metastasis (TNM) stages. K-M curves illustrated that circRNA ciRS-7 high expression was correlated with both shorter DFS and OS, and multivariate Cox's proportional hazards regression analysis showed that circRNA ciRS-7 high expression was an independent factor for predicting unfavorable DFS and OS. Cells methods revealed that circRNA ciRS-7 expression was elevated in NSCLC cell lines (A549, PC9, NCI-H1299 and NCI-H1650) compared to normal lung epithelial cells (DEAS-2B), and the inhibition of circRNA ciRS-7 expression reduced cells proliferation and promoted cells apoptosis in A549 cells. CircRNA ciRS-7 overexpression is associated with advanced disease and poor prognosis in NSCLC patients, and the down-regulation of circRNA ciRS-7 inhibits tumor cells proliferation as well as improves cells apoptosis.

Elevated PHD2 expression might serve as a valuable biomarker of poor prognosis in lung adenocarcinoma, but no lung squamous cell carcinoma.

Using data from The Cancer Genome Atlas (TCGA), we aimed to explore the association between Egl nine homolog 1 (EGLN1/PHD2) expression and survival outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. A retrospective study was conducted based on the level-3 data in the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC and data from the Human Protein Atlas (HPA). Both LUAD and LUSC had elevated PHD2 expression compared to their respective adjacent normal tissues. However, Kaplan-Meier survival curves showed that the high PHD2 expression LUAD patients had a significantly shorter overall survival (OS) and recurrence-free survival (RFS) (p=0.001 and p<0.001) compared to the low expression group. However, these differences were not observed in LUSC patients. Univariate and multivariate analysis showed that high PHD2 expression was an independent indicator of unfavorable OS (HR: 1.685, 95%CI: 1.251-2.269, p=0.001) and unfavorable RFS (HR: 2.008, 95%CI: 1.430-2.818, p<0.001) in LUAD patients. The methylation status of two CpG sites (cg07040244 and cg21875980) in PHD2 was at least moderately and negatively correlated with PHD2 expression. High methylation level of these two CpG sites was associated with better OS in LUAD patients. Elevated PHD2 expression might only serve as a valuable biomarker of poor prognosis in LUAD, but no in LUSC. Cg07040244 and cg21875980 might be two CpG sites modulating PHD2 expression in LUAD.

The prognostic value of lymph node ratio for local advanced gastric cancer patients with adjuvant chemoradiotherapy after D2 gastrectomy.

This study aimed to find the prognostic factors of local advanced gastric cancer patients with adjuvant concurrent chemoradiotherapy after radical D2 gastrectomy, and explore the prognostic value of lymph node ratio (LNR).We retrospectively analyzed 164 gastric cancer patients enrolled in West China Hospital from 2006 to 2013, who underwent D2 radical gastrectomy and adjuvant chemoradiotherapy. With univariate analysis and the Cox regression model, we evaluated the association of LNR and other clinical pathological characteristics with overall survival (OS) and relapse-free survival (RFS) of patients.Of 164 gastric cancer patients, the median age at diagnosis was 60 (IQR 51–66), with 121 males (73.78%) and 43 females (26.22%). The median follow-up time was 41.5 months. One-year and 3-year OS rate of the whole cohort was 97.6% and 88.4%, with 1-year RFS rate of 90.2% and 3-year RFS rate of 76.8%, respectively. In the univariate analysis, we found that age >60years (P = .025), TNM stage III (P = .014), LNR >0.25 (P = .006) and radiation dose <45Gy (P = .048) predicted worse OS. Further multivariate analysis indicated that age >60y (HR 2.375, 95% CI 1.100–5.128; P = .028), TNM stage III (HR 7.692, 95% CI 1.009–58.824; P = .049) and LNR >0.25 (HR 2.439, 95% CI 1.075–5.525; P = .033) were independent prognostic factors for unfavorable OS. The COX analysis showed that related prognostic factors of worse RFS were TNM stage III (HR 3.802, 95% CI 1.506–9.615; P = .049) and LNR >0.25 (HR 2.326, 95% CI 1.332–4.065; P = .003).LNR can be used as an important prognostic indicator for gastric cancer patients with D2 resection and adjuvant chemoradiotherapy, and LNR more than 0.25 indicates poor prognosis.

Prognostic impact of preoperative prognostic nutritional index in resected advanced gastric cancer: A multicenter propensity score analysis

BackgroundAdvanced gastric cancer (AGC) causes debilitating malnutrition and leads to deterioration of the immune response. However, the concept of the prognostic nutritional index (PNI) is controversial when applied to patients with AGC. The aim of the present study was to evaluate the effect of the PNI after gastrectomy in patients with AGC. Materials and methodsA multicenter retrospective study was conducted using propensity score matching (PSM) in gastric adenocarcinoma patients who underwent resection via laparoscopic or open surgery between 2014 and 2017. To overcome selection bias, we performed 1:1 matching using 5 covariates. ResultsThe resection margins (P < 0.001) and LNM (P = 0.004) were significantly different between the two groups. In univariate analysis, poor tumor differentiation (P = 0.038) (R1+R2, P = 0.004), vascular and neural invasion (P < 0.001), and a PNI<50 (P < 0.001) were associated with poor recurrence-free survival (RFS). In multivariate analysis, a PNI<50 (hazard ratio (HR), 12.993; P < 0.001) was a risk factor for RFS. Univariate analysis for overall survival (OS) revealed that a PNI<50 (P < 0.001) (R1+R2,P = 0.006) and vascular and neural invasion (P < 0.001) were risk factors. In subsequent multivariate analysis, a PNI<50 (HR, 24.501; P < 0.001) was a significant risk factor for OS. Clinical assessments performed during a 12.34 (±5.050) month follow-up revealed that OS (P < 0.001) and RFS (P < 0.001) were worse in patients with a low PNI (<50) than in matched patients with a high PNI. ConclusionA low PNI is a strong predictor of unfavorable RFS and OS in patients with AGC.

SIRT1 in Secretory Organ Cancer.

Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors [1, 2, 3, 4]. A recent meta-analysis conducted on 37 selected studies of human cancers analyzed the correlations of overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) with SIRT1 expression [5]. This study reported that SIRT1 overexpression was associated with a worse OS in liver and lung cancers, while it was not correlated with OS in breast cancer, colorectal cancer, or gastric carcinoma. Collectively, the meta-analysis revealed that an unfavorable OS was associated with SIRT1 expression for solid malignancies. Given the growing importance of this class of lysine/histone deacetylases in human endocrine malignancies, a rational and focused literature assessment is desirable in light of future clinical translations.

Prognostic value of prognostic nutritional index in lung cancer: a meta-analysis.

Previous studies reported pretreatment prognostic nutritional index (PNI) was associated with clinical outcome of lung cancer. However, the result was not conclusive. We conducted a comprehensive meta-analysis to clarify the impact of PNI in lung cancer prognosis. We identified eligible studies by searching PubMed, EMBASE, and Web of Science, up to August 15, 2017. Overall survival (OS) and clinicopathological characteristics were collected from included studies. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were used to estimate clinical and prognostic value of PNI in lung cancer. Ten studies including 5,085 patients were enrolled in the meta-analysis. The result demonstrated that low PNI was correlated with unfavorable OS in lung cancer (HR =1.72; 95% CI, 1.43-2.06; P=0.000), especially among non-small cell lung cancer patients (HR =1.93; 95% CI, 1.56-2.37; P=0.000). As for clinical characteristics, low PNI status was found related to gender (female versus male, HR =0.68; 95% CI, 0.554-0.857; P=0.001) and histology (adenocarcinoma versus non-adenocarcinoma, HR =0.59; 95% CI, 0.47-0.74, P=0.000), but not smoking status (smoker versus never smoker, HR =1.49; 95% CI, 0.99-2.25, P=0.056). No significant publication bias was found (P=0.210). PNI was an independent prognostic indicator for lung cancer, and can serve as a novel biomarker to help guide clinical practice and promote clinical outcomes of lung cancer patients.

Pathologically examining a minimum of three lymph nodes could better determine node negativity in patients with non-metastatic chromophobe renal cell carcinoma.

To evaluate the prognostic value of lymph node (LN) involvement for patients with chromophobe renal cell carcinoma (chRCC) and ascertain the minimum number of LNs that need to be pathologically examined to reliably diagnose a patient with node negative chRCC. From 2004 to 2014, non-metastatic chRCC patients receiving radical nephrectomy together with lymphadenectomy were identified from the Surveillance, Epidemiology and End Results (SEER) database. The primary outcome was overall survival (OS). Two hundred and forty-six patients received lymph node dissection during the surgery. Of the patients, 24 (10%) had pathologically confirmed positive LN. Multivariate Cox regression model showed that positive LN was an independent unfavorable predictor for OS (HR = 2.83, 95%CI = 1.14-6.98, P = 0.024). More importantly, LN(-) patients with at least three LNs dissected had significantly better OS compared with when 1-2 LNs were examined (P = 0.048). Multivariate analysis confirmed that in LN(-) patients, the examination of three or more LNs could independently predict better OS compared with patients with only 1-2 LNs dissected (HR≥3LNs = 0.362, 95% CI = 0.135-0.972, P = 0.044). Additionally, the likelihood of finding at least one positive LN was significantly higher on dissection of ≥3 LNs compared with examination of 1-2 LNs (15% vs 5%, P = 0.018). Decision curve analysis found a better clinical validity of the '3 LNs examined'-based classification compared with the traditional LN(-)/LN(+) classification. The proportion of positive LNs in chRCC was far from neglectable and LN metastasis could independently predict unfavorable OS. We recommended a minimum of three LNs should be pathologically examined in order to reliably determine node negative.

Low serum cholesterol levels predict inferior prognosis and improve NCCN-IPI scoring in diffuse large B cell lymphoma.

Low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. However, the association between cholesterol levels and diffuse large B cell lymphoma (DLBCL) remains unknown. The aim of our study was to evaluate the prognostic value of serum lipid profile in DLBCL. Five hundred and fifty enrolled subjects with detailed serum lipid levels at diagnosis of DLBCL were randomly divided into a training set (n = 367) and a validation set (n = 183) (ratio, 2:1). Multivariate Cox regression analyses screened the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Performances of models were compared using C-index and area under the curve in internal and external validation. The results showed that decreased levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were associated with unfavorable PFS and OS in the rituximab era, and concurrently low HDL-C together with low LDL-C was an independent prognostic indicator for both PFS and OS. Patients achieving complete remission or partial remission after 6-8 circles of chemotherapies had significantly increased cholesterol levels compared to the levels at DLBCL diagnosis, and HDL-C or LDL-C elevations were correlated with better survival. Furthermore, the predictive and discriminatory capacity of the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) together with low cholesterol levels was superior to NCCN-IPI alone both in the training and validation set. In conclusion, serum cholesterol levels are simple and routinely tested parameters, which may be good candidates for predicting prognosis in the future clinical practice of DLBCL.

Prognostic Role of Platelet-to-Lymphocyte Ratio in Hepatocellular Carcinoma with Different BCLC Stages: A Systematic Review and Meta-Analysis

The role of platelet-to-lymphocyte ratio (PLR) in the prognosis of hepatocellular carcinoma (HCC) patients with different Barcelona Clinic Liver Cancer (BCLC) stages remains controversial. This systematic review and meta-analysis aimed to determine the efficacy of PLR on HCC prognosis. Five electronic databases were searched for clinical trials focusing on the role of PLR in the prognosis of HCC. A total of 297 potential studies were initially identified, and 9 studies comprising 2449 patients were finally enrolled to evaluate the association between the pretreatment PLR and clinical outcomes of overall survival (OS), disease-free survival (DFS), and event occurrence in patients with HCC in different BCLC stages. An elevated pretreatment PLR indicated unfavorable worse OS (HR = 1.73; 95% CI: (1.46, 2.04); P < 0.00001) and DFS (HR = 1.30; 95% CI: (1.06, 1.60); P = 0.01). Subgroup analysis indicated that high PLR indicated poor OS among BCLC-B/C patients without heterogeneity, while PLR in BCLC-A patients indicated high statistical heterogeneity with I2 value of 78%. As for the correlation between PLR and event occurrence, high PLR was related to poor clinical event occurrence only among BCLC-C patients, though obvious heterogeneity was observed in all different BCLC stages. In conclusion, PLR may be a significant biomarker in the prognosis of HCC in different BCLC stages.

The correlation of circulating pro-angiogenic miRNAs' expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer.

This study aimed to explore the correlation of circulating pro‐angiogenic miRNAs’ expressions with risk, clinicopathological features, and survival profiles in gastric cancer (GC). Three hundred and thirty‐three GC patients underwent radical resection and 117 health controls (HCs) were recruited for this study. Plasma samples were obtained from GC patients before the operation and from HCs after enrollment. Fourteen pro‐angiogenic miRNAs were asseassed by quantitative polymerase chain reaction (qPCR). Disease‐free survival (DFS) and overall survival (OS) of GC patients were calculated and the median follow‐up duration was 36.0 months. Seven out of 14 pro‐angiogenic miRNAs including let‐7f, miR‐17‐5p, miR‐18a, miR‐19b‐1, miR‐20a, miR‐210, and miR‐296 were observed to be elevated in GC patients compared with HCs. MiR‐18a, miR‐20a, and miR‐210 disclosed good predictive values of GC risk. Six pro‐angiogenic miRNAs including miR‐17‐5p, miR‐92a, miR‐210, miR‐20a, miR‐18a, and miR‐296 expressions were positively while 1 pro‐angiogenic miRNA (miR‐130a) was negatively correlated with tumor malignancy degree in GC patients. K‐M curve disclosed that 5 pro‐angiogenic miRNAs including miR‐17‐5p, miR‐18a, miR‐20a, miR‐92a, and miR‐210 correlated with worse DFS, while 4 pro‐angiogenic miRNAs including miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 associated with shorter OS. Further multivariate Cox's analysis revealed that miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 were independent predictive factors for unfavorable DFS and OS. In conclusion, circulating pro‐angiogenic miRNAs could serve as novel noninvasive biomarkers for disease risk and malignancy degree, and miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 are independent factors predicting poor prognosis in GC patients.

Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma.

S100A16 is a conserved member of the S100 protein family in mammals. Its upregulation was observed in many tumors and is related to malignant transformation. In this study, we explored the independent prognostic value of S100A16 in terms of overall survival (OS) and recurrence-free survival (RFS) by performing a retrospective study, using data in The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD). Besides, by using deep sequencing data in TCGA-LUAD, we also explored the association between S100A16 expression and its DNA methylation and copy number alterations (CNAs). Results showed that the primary LUAD tissues (N = 514) had significantly elevated S100A16 expression compared with the normal lung tissues (N = 59). Based on OS data of 502 primary LUAD cases, we found that high S100A16 expression was correlated with inferior OS. The following univariate and multivariate analysis confirmed that increased S100A16 expression was an independent prognostic indicator of unfavorable OS (HR: 1.197, 95%CI: 1.050–1.364, p = 0.007) and RFS (HR: 1.206, 95%CI: 1.045–1.393, p = 0.011). By examining the DNA methylation data in TCGA-LUAD, we found that some S100A16 DNA CpG sites were generally hypermethylated in normal tissues, but not in LUAD tissues. Regression analysis identified a moderately negative correlation between S100A16 expression and its DNA methylation. In comparison, although DNA amplification (+1/+2) was frequent (378/511, 74%) in LUAD patients, it was not associated with increased S100A16 expression. Based on findings above, we infer that aberrant S100A16 expression might be modulated by its DNA hypomethylation and serves as an independent prognostic indicator of unfavorable OS and RFS in LUAD.

Prognostic values of aquaporins mRNA expression in human ovarian cancer.

Aquaporins (AQPs), a family of transmembrane channel, are composed of 13 identified members (AQP0–12). Accumulating evidences reported that AQPs were correlated with various biological roles and represented a prognostic predictor in various cancer types. However, the prognostic value of AQPs expression in ovarian cancer remains unclear. Using ‘Kaplan–Meier plotter’ (KM plotter) online database, we explored the predictive prognostic value of individual AQPs members’ mRNA expression to overall survival (OS) in different clinical data, such as histology, pathological grades, clinical stages, TP53 status, and applied chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0, AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3, AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients. Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8, and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable OS in all patients treated with Platin chemotherapy. Our results suggest that individual AQPs, except AQP2 and AQP9, are associated with unique prognostic significance and may thus act as new predictive prognostic indicators and potential drug therapeutic target in ovarian cancer.