Novel Predictor Of Prognosis Research Articles

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood.MethodsTo address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue.ResultsThrough the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs.ConclusionsThis study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Circulating sNinj1 as a novel predictor of prognosis and severity in hepatocellular carcinoma

BackgroundThe occurrence and development of HCC are closely associated with cell death. Recently, researchers found that Ninj1 plays a pivotal role in PMR during different types of cell death. However, the importance of Ninj1 in HCC has not been extensively investigated. MethodsThis study included 102 newly diagnosed HCC patients and 102 sex and age-matched NCs. Circulating sNinj1 was assessed by ELISA. Serum LDH and IL-1ß were detected through a chemiluminescence assay. The correlations of these biomarkers with disease severity and their potential as prognostic predictors for HCC were evaluated. The dynamic changes of sNinj1, LDH, and IL-1ß levels before and after treatment were recorded. ResultsSerum levels of sNinj1, IL-1ß, and LDH were significantly higher in HCC patients. Our study found that the sNinj1 level was positively correlated with tumor size, metastasis, and staging. ROC analysis indicated that the AUC of sNinj1 in differentiating HCC from NCs was 0.85. As a result of tumor thrombosis and invasion of the hepatic vein, sNinj1′s AUCs were 0.71 and 0.73, respectively. After partial resection and TACE treatment, serum sNinj1 and LDH exhibited similar change trends. A one-year follow-up analysis also demonstrated that HCC patients with high sNinj1 had significantly poorer survival than those with low sNinj1. ConclusionsThe serum sNinj1 is another diagnostic biomarker supporting the HCC diagnosis. More importantly, it has been shown that circulating sNinj1 reveals potential as a novel predictor of HCC severity and prognosis.

Controlling Nutritional Status (CONUT) score as a prognostic marker for gastrointestinal stromal tumours.

The Controlling Nutritional Status (CONUT) score, regarded as the effective indicator of patient nutrition, has been demonstrated to be related to prognosis of numerous tumours. Nevertheless, the significance of CONUT for gastrointestinal stromal tumour (GIST) remains unclear. This study intended to clarify the association between CONUT and the prognosis of GISTs. Three hundred and fifty-five patients with GISTs undergoing surgical resection at our center were retrospectively assessed. Receiver operating characteristic curve analysis was used to help determine the cut-off value of CONUT score. Relapse-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier curve analysis. Prognostic factors for RFS and OS were examined by Cox proportional hazards models. A total of 355 patients were enrolled in this study. Areas under the curve (AUC) were 0.638 for CONUT score, and the cut-off value of CONUT was shown to be three. Kaplan-Meier curve analysis showed that high CONUT score was linked to poorer RFS and OS. Univariate and multivariate analyses ultimately revealed that CONUT was a risk factor for RFS and OS, independent of demographics and clinicopathological tumour characteristics. CONUT score was an effective and novel predictor for prognosis of GIST patients treated with surgery, indicating its potential as a prognostic marker in the overall management.

APOA4 as a novel predictor of prognosis in Stevens-Johnson syndrome/toxic epidermal necrolysis: A proteomics analysis from two prospective cohorts

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects. To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms. We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis. The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P=.004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P=.118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols. The cohort size is relatively small. Both cohorts had low overall SCORTEN scores. Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN.

The Cancer-Associated Fibroblasts-Related Gene COMP Is a Novel Predictor for Prognosis and Immunotherapy Efficacy and Is Correlated with M2 Macrophage Infiltration in Colon Cancer.

Colon cancer is characterized by a sophisticated tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which make up the majority of the stromal cells in TME, participate in tumor development and immune regulation. Further investigations of CAFs would facilitate an in-depth understanding of its role in colon cancer TME. In this study, we estimated CAF abundance based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases using the Microenvironment Cell Populations-counter (MCP-counter) algorithm. CAF-related genes were identified by differential gene expression analysis combined with weighted gene coexpression network analysis. For further selection, the least absolute shrinkage and selection operator (LASSO)-Cox regression was used, and the prognostic value of the selected gene was confirmed in numerous external cohorts. The function enrichment, immunological characteristics, tumor mutation signature, immunotherapy response, and drug sensitivity of the selected gene were subsequently explored. The bioinformatics analysis results were validated using immunohistochemistry on clinical samples from our institution. According to our findings, cartilage oligomeric matrix protein (COMP) was uncovered as a candidate CAFs-driven biomarker in colon cancer and plays an important role in predicting prognosis in colon cancer. COMP upregulation was associated with enhanced stromal and immune activation, and immune cell infiltration, especially M2 macrophages. Genes that mutated differently between the high- and low-COMP expression subgroups may be correlated with TME change. Following verification, COMP reliably predicted the immunotherapy response and drug response. In addition, our experimental validation demonstrated that COMP overexpression is associated with colon cancer carcinogenesis and is strongly associated with CAFs and M2 macrophage infiltration. Our study uncovered that COMP was a key CAFs-driven gene associated with M2 macrophage infiltration and acted as a convincing predictor for prognosis and immunotherapy response in colon cancer patients.

Red Cell Distribution Width to Platelet Ratio Is Associated with Increasing In-Hospital Mortality in Critically Ill Patients with Acute Kidney Injury.

Background Inflammation plays a key role in the pathophysiology and progression of acute kidney injury (AKI). Red cell distribution width (RDW) to platelet ratio (RPR) is a novel inflammatory index, and its prognostic effect on critically ill patients with AKI is rarely investigated. This work is aimed at investigating the association between RPR and in-hospital mortality in these patients. Methods Data were extracted from the Medical Information Mart for Intensive Care III database. All-cause death during hospitalization was selected as the primary outcome. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, and the area under the curve (AUC) was applied to compare predictive ability among different indices. Cox proportional hazard models were utilized to assess the association between RPR and in-hospital mortality. Restricted cubic spline analysis for multivariate Cox model was performed to explore the shape of the relationship between RPR and mortality. Results A total of 24,166 critically ill patients with AKI were included. The relationship of RPR and in-hospital mortality was nonlinear with a trend to rise rapidly and then gradually. For mortality prediction, RPR had the optimal cut-off value of 0.093, of which the AUC was 0.791 (95% confidence interval (CI): 0.773–0.810), which was higher than those of RDW, platelet, sequential organ failure assessment score, simplified acute physiology score II, neutrophil to lymphocyte ratio, and platelet to lymphocytes ratio. After adjustments for various confounders, high RPR showed a significant association with increased mortality with hazard ratios of 1.46 (95% CI: 1.40–1.55) for categorical variable and 1.88 (95% CI: 1.80–1.97) for continuous variables in the fully adjusted model. Conclusions Elevated RPR on admission is substantially associated with high risk of in-hospital mortality in critically ill patients with AKI and thus may serve as a novel predictor of prognosis for these patients.

Identification of an Immune-Related Long Noncoding RNA Pairs Model to Predict Survival and Immune Features in Gastric Cancer.

Background: Gastric cancer (GC) remains one of the most malignant tumors around the world, and an accurate model that reliably predicts survival and therapeutic efficacy is urgently needed. As a novel predictor for prognosis in a variety of cancers, immune-related long noncoding RNA pairs (IRlncRNAPs) have been reported to predict tumor prognosis. Herein, we integrated an IRlncRNAPs model to predict the clinical outcome, immune features, and chemotherapeutic efficacy of GC.Methods: Based on the GC data obtained from The Cancer Genome Atlas (TCGA) database and the Immunology Database and Analysis Portal (ImmPort), differentially expressed immune-related long noncoding RNAs (DEIRlncRNAs) were identified. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis were used to select the most appropriate overall survival (OS)-related IRlncRNAPs to develop a prognostic signature. The riskScore of each sample was calculated by comparing the long noncoding RNA expression level in each IRlncRNAP. Based on the riskScore for each patient, GC patients were divided into high- and low-risk groups. Then, the correlation of the signature and riskScore with OS, clinical features, immune cell infiltration, immune-related gene (IRG) expression and chemotherapeutic efficacy in GC was analyzed.Results: A total of 107 DEIRlncRNAs were identified which formed 4297 IRlncRNAPs. Fifteen OS-related IRlncRNAPs were selected to develop a prognostic model. GC patients could be accurately classified into high- and low-risk groups according to the riskScore of the prognostic model. The 1-, 2-, 3-, and 5-year receiver operating characteristic (ROC) curves for the riskScore were drawn and the area under the curve (AUC) values were found to be 0.788, 0.810, 0.825, and 0.868, respectively, demonstrating a high sensitivity and accuracy of this prognostic signature. Moreover, the immune-related riskScore was an independent risk factor. Patients showed a poorer outcome within the high-risk group. In addition, the riskScore was found to be significantly correlated with the clinical features, immune infiltration status, IRG expression, and chemotherapeutic efficacy in GC.Conclusion: The prognostic model of IRlncRNAPs offers great promise in predicting the prognosis, immune infiltration status, and chemotherapeutic efficacy in GC, which might be helpful for the selection of chemo- and immuno-therapy of GC.

Myosteatosis as a novel prognostic biomarker after radical cystectomy for bladder cancer

This study aims to evaluate the influence of myosteatosis on survival of patients after radical cystectomy (RC) for bladder cancer. We retrospectively identified 230 patients who underwent RC for bladder cancer at our three institutions between 2009 and 2018. Digitized free-hand outlines of the left and right psoas muscles were made on axial non-contrast computed tomography images at level L3. To assess myosteatosis, average total psoas density (ATPD) in Hounsfield Units (HU) was also calculated as an average of bilateral psoas muscle density. We compared cancer-specific survival (CSS) between high ATPD and low ATPD groups and performed cox regression hazard analyses to identify the predictors of CSS. Median ATPD was 44 HU (quartile: 39–47 Hounsfield Units). Two-year CSS rate in overall patients was 76.6%. Patients with low ATPD (< 44 HU) had significantly lower CSS rate (P = 0.01) than patients with high ATPD (≥ 44 HU). According to multivariate analysis, significant independent predictors of poor CSS were: Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.03), decreasing ATPD (P = 0.03), non-urothelial carcinoma (P = 0.01), pT ≥ 3 (P < 0.01), and pN positive (P < 0.01). In conclusion, myosteatosis (low ATPD) could be a novel predictor of prognosis after RC for bladder cancer.

Expression of PD-L1 on Monocytes Is a Novel Predictor of Prognosis in Natural Killer/T-Cell Lymphoma.

Background: Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive lymphoma with a dismal prognosis, and novel therapeutic targets are urgently needed. Programmed death-ligand 1 (PD-L1) has become a promising therapeutic target for various cancers, but most of the studies have focused on expression of PD-L1 on tumor cells. Expression of PD-L1 on tumor-infiltrating non-malignant cells, especially monocytes, has not been studied in NKTCL, and its prognostic value remains unknown.Materials and Methods: Expression of PD-L1 on tumor-infiltrating stromal cells was measured in NKTert and HS5 cells when cultured alone or co-cultured with NKTCL cell lines. Clinical samples were collected from 42 patients with newly diagnosed NKTCL. Expression of PD-L1 on monocytes was analyzed in patients' peripheral blood and tumor tissues using flow cytometry and immunofluorescent staining, respectively. Survival data were retrospectively collected and the prognostic significance of PD-L1 expression on monocytes was analyzed.Results: PD-L1 expression on tumor-infiltrating stromal cells was remarkably elevated when co-cultured with NKTCL cells. The percentage of PD-L1+ monocytes among all monocytes in peripheral blood was significantly higher in NKTCL patients than that in healthy individuals. Among NKTCL patients, percentage of PD-L1+ monocytes in blood positively correlated with that in tumor tissues. Patients with a higher percentage (≥78.2%) of PD-L1+ monocytes in blood or with a higher percentage (≥24.2%) of PD-L1+ monocytes in tumor tissues exhibited a significantly inferior survival, compared with their counterparts. A higher percentage of PD-L1+ monocytes in blood or tumor tissues was an independent adverse prognostic factor.Conclusions: Expression of PD-L1 on monocytes is up-regulated and has significant prognostic value in patients with NKTCL.

High expression levels of TLR9 and PD-L1 indicates a poor prognosis in patients with angioimmunoblastic T-cell lymphoma: a retrospective study of 88 cases in a single center.

Background: The role of TLR9 expressed by tumor cells in evading immune surveillance was confirmed. PD-L1 expression in tumor cells plays a key role in tumor immune escape, which is associated with poor prognosis. However, the clinical relevance of TLR9 and PD-L1 expression in angioimmunoblastic T-cell lymphoma (AITL) has not been evaluated.Materials and methods: In this study, we identified differentially expressed genes in AITL samples by bioinformatic analysis, and we first examined TLR9 and PD-L1 expression by immunohistochemical staining in patients with AITL and compared these data with clinical features and survival time.Results: It was found that the expression of PD-L1 and multiple TLRs was higher in AITL than normal T-cell samples, and TLR9 and PD-L1 expression displayed complex interactions by bioinformatic analysis. The rates of TLR9 and PD-L1 high expression were 69% and 50%, respectively. High expression of either TLR9 or PD-L1 indicated a poor survival rate for patients with AITL. Multivariate analysis further confirmed that high expression levels of TLR9 and PD-L1 were unfavorable prognostic factors for AITL. We further found inferior overall survival in AITL with clinical features of ECOG status ≥ 2, advanced-stage, elevated serum LDH levels, elevated serum β2-MG levels, and high IPI score.Conclusion: TLR9 and PD-L1 expression may be a novel predictor of prognosis for patients with AITL and may serve as potential therapeutic strategy.

Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1 (PREX1) is a Novel Predictor of Prognosis for Breast Cancer Patients: A Retrospective Case Series.

BackgroundIn previous studies, higher expression of PREX1 (PtdIns (3,4,5)P3-dependent Rac exchanger 1) has been detected in some subsets of breast cancer, and activation of PREX1 has been associated with tumor progression in vivo. However, an association between PREX1 and breast cancer prognosis has not been examined.Material/MethodsIn this study, we investigated the expression and correlation of PREX1 with important clinical factors and prognosis of patients with breast cancer. Immunohistochemical staining was performed for 121 tumor tissue specimens obtained from primary breast cancer lesions.ResultsWe found that 55 tissues exhibited positive staining for PREX1. Moreover, tumors positive for PREX1 were found to have significant association with recurrence rate (P=0.000) and metastasis rate (P=0.001). Univariate and multivariate regression analyses also identified PREX1 expression as an independent variable of disease-free survival. Our analyses indicate that high levels of PREX1 expression were related to longer disease-free survival in patients with breast cancer (P=0.013).ConclusionsPREX1 is a favorable variable of prognosis for breast cancer patients, these study results need to be confirmed in larger research studies.

Overexpression levels of cripto-1 predict poor prognosis in patients with prostate cancer following radical prostatectomy.

Overexpression of cripto-1 (CR-1), an epidermal growth factor-cripto-1/FRL-1/Cryptic family protein, has been reported in multiple types of malignancy. However, the clinical functions of CR-1 in prostate cancer (PCa) remain largely unclear. The objective of the present study was to investigate the association between CR-1 expression and the clinicopathological features and prognosis of PCa. CR-1 expression was evaluated in 138 PCa tissues and 67 benign prostate hyperplasia (BPH) tissues using immunohistochemistry. The association between the clinicopathological features of patients with PCa and CR-1 expression was analyzed using a χ2 test. Receiver operating characteristic (ROC) curve and Cox regression model were used to analyze the association between CR-1 expression and biochemical recurrence (BCR)-free survival. It was revealed that the protein expression of CR-1 was markedly higher in PCa tissues than in BPH tissues. The mRNA expression of CR-1 in PCa tissue and cells was also significantly higher than in BPH tissue and the normal RWPE-1 prostate cell line (P<0.05). In addition, high CR-1 expression was significantly associated with prostate-specific antigen level (P=0.008), Gleason score (P=0.011) and lymph node metastasis (P=0.025) in patients with PCa. ROC curve indicated that patients with elevated expression of CR-1 exhibited shorter BCR-free survival (P<0.001). Furthermore, multivariate statistical analysis demonstrated that overexpression of CR-1 may be a novel predictor for prognosis of patients with PCa. Accordingly, the present study considered CR-1 to be a valuable predictor of poor prognosis and progression in PCa, and a potential therapeutic target for patients with PCa.

Lymphoid-specific helicase promotes the growth and invasion of hepatocellular carcinoma by transcriptional regulation of centromere protein F expression.

Lymphoid‐specific helicase (LSH) is overexpressed in tumor tissues and its overexpression is associated with poor prognosis in several cancers. However, the role and molecular mechanism of LSH in hepatocellular carcinoma (HCC) remains largely unknown. Herein, we report that LSH was overexpressed in tumor tissues of HCC, and overexpression of LSH was associated with poor prognosis from a public HCC database, and validated by clinical samples from our department. Ectopic LSH expression promoted the growth of HCC cells in vivo and in vitro. Mechanistically, LSH overexpression promoted tumor growth by activating transcription of centromere protein F (CENPF). Clinically, overexpression of LSH and/or CENPF correlated with shorter overall survival and higher cumulative recurrence rates of HCC. In conclusion, LSH promotes tumor growth of HCC through transcriptional regulation of CENPF expression. Therefore, LSH may be a novel predictor for prognosis and a potential therapeutic target for HCC.

Overexpression of CUL4B is a novel predictor of prognosis for endometrial adenocarcinoma

Overexpression of CUL4B is a novel predictor of prognosis for endometrial adenocarcinoma

Positive expression of ZNF689 indicates poor prognosis of hepatocellular carcinoma.

The objective of the present study was to investigate the association between zinc finger protein (ZNF) 689 expression and the clinicopathological features and prognosis of hepatocellular carcinoma (HCC). A total of 102 paired HCC and paired non-cancerous tissues, and 16 normal liver tissues were collected. ZNF689 expression was examined in HCC tissues, paired-noncancerous tissues, and normal liver tissues using RT-qPCR and immunohistochemistry analysis, and the association between ZNF689 expression and HCC prognosis was analyzed using the Kaplan-Meier method. ZNF689 expression was not significantly different between HCC tissues and paired-noncancerous tissues (P=0.61). ZNF689 expression in HCC and paired-noncancerous tissues was significantly increased compared with that in normal liver tissues (P<0.01). Positive expression of ZNF689 protein in HCC was significantly associated with a tumor size of ≥10 cm, tumor capsule infiltration, and microvascular invasion (P<0.05). Positive expression of ZNF689 was a prognostic factor for overall survival time [hazard ratio (HR):1.961; P=0.048] and progression-free survival time (HR:1.902; P=0.041). ZNF689 maybe a novel predictor for prognosis of patients with HCC.

Significance of Methylation of FBP1 Gene in Non-Small Cell Lung Cancer.

Because NSCLC has poor overall prognosis and is frequently diagnosed at later stage, we aimed to seek novel diagnosis biomarkers or therapy target of the disease in this study. Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis, which was usually lost in NSCLC due to abnormal methylation in promoter DNA sequence. The clinical data indicated that the methylation rate in FBP1 gene promoter was negatively related to the overall survival of the NSCLC patients. DNA methylation transferase inhibitor 5-aza treatment could significantly increase both expression levels of mRNA and protein in A549 cell line. On the other hand, silence of FBP1 in H460 cell line by using specific siRNA against FBP1 dramatically improved the cell proliferation and cell migration according to the date of FACS and transwell assays. All these findings implied the important roles of FBP1 expression in lung cancer development and progression and the potential use of the methylation status detected in FBP1 promoter region as a novel predictor for prognosis and therapeutic target for NSCLC patients.

Tumor-stroma ratio(TSR) as a potential novel predictor of prognosis in digestive system cancers: A meta-analysis

Main problemThe tumor-stroma ratio (TSR) has been reported as a prognosis predictor in multiple cancers. The aim of this meta-analysis was to investigate the potential value of TSR as a prognostic predictor of cancer in the digestive system. MethodsWe searched PubMed, Embase, Elsevier and Web of Science. All studies exploring the association of TSR with overall survival (OS) or disease-free survival (DFS), and lymph node metastasis (LNM) were identified. ResultsIn total, eight studies were eligible for analysis, and they included 1959 patients. Meta-analysis showed that the low TSR in the tumor could predict poor overall survival (OS) in multiple cancers (pooled Hazard Ratio [HR]: 2.15, 95%CI: 1.80–2.57, P<0.00001, fixed effects). For disease-free survival (DFS), low TSR was also a significant predictor (pooled Hazard Ratio [HR]: 2.31, 95%CI: 1.88–2.83, P<0.00001, fixed effects). In addition, low TSR was correlated with tumor stage. DiscussionThe tumor-stroma ratio (TSR) may potentially serve as a poor prognostic predictor for the metastasis and prognosis of cancer.

Prognostic value of circulating tumor cells in non-small cell lung cancer.

e20520 Background: Quantitative analysis of circulating tumor cells (CTCs) is increasingly investigated as a novel predictor of prognosis in non-small cell lung cancer (NSCLC). The primary aim of this study was to further investigate the prognostic value of CTCs enumeration in patients with advanced NSCLC. Methods: The medical records of patients with chemotherapy-naïve, advanced NSCLC and at least one available measurement of CTCs were retrospectively reviewed. The presence of CTCs was evaluated using the CellSearch system. A cut-off point of 2 CTCs ( &lt; 2 vs ≥2 ) was used to discriminate between negative and positive samples, respectively. The detection of CTCs was correlated with the clinicopathological features of patients and outcome. Results: Our study population comprised a total of 43 patients (mean age 67.1±9.9 years; male/female ratio: 39/4). Eight out of 43 patients (18.6%) harbored CTCs. No significant associations were found between treatment response and baseline count of circulating tumor cells (CTCs) (p = 0.067). Positive CTC count was associated with the presence of five or more metastatic sites (p = 0.018). Neither PFS nor OS were found to differ significantly between CTC-positive and CTC-negative cases (log-rank p = 0.079 and 0.549, respectively). The presence of five or more metastatic sites and worse PS were recognized as independent predictors of reduced PFS [HR = 2.9, p = 0.042 and HR = 2.7, p = 0.035, respectively], and reduced OS [HR = 7.8, p = 0.003 and HR = 16.9, p &lt; 0.001, respectively]. Conclusions:CTCs were detected in a relatively small percentage of our patient population and their presence was associated with increased metastatic burden. In contrast, we failed to observe any significant associations between baseline CTC count and the prognostic variables evaluated. Our results support the suggested role of CTCs in the metastatic dissemination of cancer and underline the need for more efficient methods of CTCs detection.

Phosphorylated eIF2\u03b1 predicts disease-free survival in triple-negative breast cancer patients

Phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), which functions as a marker of endoplasmic reticulum stress, has been reported to be associated with patient prognosis in various cancers. However, little is known about the prognostic value of p-eIF2α in breast cancer, particularly in different breast cancer subtypes. An immunohistochemistry screen for p-eIF2α was performed using a tissue microarray containing 233 tumors and paired peritumoral tissues from female patients diagnosed with breast cancer. The staining results were scored semiquantitatively, and the p-eIF2α expression level in breast cancer and its potential prognostic value were investigated. In this retrospective cohort study, we found that p-eIF2α levels were significantly upregulated in breast cancer (P < 0.001). p-eIF2α level was negatively correlated with lymph node status (P = 0.039). Survival analysis by Kaplan–Meier estimation and Cox regression showed that p-eIF2α level was correlated with better disease free survival (P = 0.026) and served as an independent prognostic factor (P = 0.046) in patients with triple-negative breast cancer. Our study revealed that p-eIF2α was upregulated in breast cancer and represented a novel predictor of prognosis in patients with triple-negative subtype.

Cervical cancer systemic inflammation score: a novel predictor of prognosis

Inflammation contributes to development and progression in a variety of cancers, including cervical cancer. We developed a novel cervical cancer systemic inflammation score (CCSIS) based on the preoperative platelet-to-lymphocyte ratio (PLR) and serum albumin levels. A retrospective analysis of clinical data from 795 patients with operable cervical cancer was then conducted to investigate the prognostic value of CCSIS and its association with the patients' clinicopathological features, overall survival (OS), and disease-free survival (DFS). CCSIS was predictive of OS and DFS. High CCSIS was correlated with more advanced FIGO stages, poor tumor differentiation, and the presence of PLN and LVSI. Both albumin levels and the PLR were independent prognostic indicators for operable cervical cancer. The use of the CCSIS could improve risk stratification and traditional clinicopathological analysis in cervical cancer.