Independent Prognostic Biomarker For Overall Survival Research Articles

ARPC1B is a novel prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune infiltration.

Background: Actin-related protein 2/3 complex subunit 1B (ARPC1B) is reported to be involved in tumorigenesis and progression. However, its role in kidney renal clear cell carcinoma (KIRC), correlation with tumor-infiltrating immune cells, and prognostic significance remain unclear. Methods: Data sets from the TCGA, GTEx, GEPIA, GEO, UALCAN, and CPTAC databases were extracted and analyzed to investigate the expression difference, prognosis, and clinicopathological features of ARPC1B. Single-sample Gene Set Enrichment Analysis (ssGSEA), CIBERSORT, and TISCH2 analysis were used to examine the relationship between ARPC1B expression and tumor immune infiltration in KIRC. The potential function of ARPC1B in KIRC was explored by GO functional annotation and KEGG pathway analysis. The TIDE algorithm was used to predict and analyze the relationship between ARPC1B expression and response to immune checkpoint blockade (ICB). The expression of ARPC1B was further validated by using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results: The study showed that ARPC1B expression was an independent prognostic factor of KIRC, with high ARPC1B expression being associated with poor overall survival (OS). Enrichment of GO annotation and pathway analysis showed multiple immune-related functional pathways affected by ARPC1B such as regulation of immune effector process, inflammatory response regulation, antigen processing and presentation, asthma, autoimmune thyroid disease, graft versus host disease, intestinal immune network for IgA production, and type I diabetic mellitus. Moreover, ARPC1B expression positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in KIRC. Importantly, high ARPC1B expression predicted a low response to ICB in KIRC. Conclusion: This study indicates that ARPC1B expression is an independent prognostic biomarker for OS in KIRC patients. High ARPC1B expression is closely associated with MDSCs and Tregs infiltration. These findings suggest that ARPC1B may serve as a biomarker for prognosis and immune infiltration in KIRC, potentially aiding in the development of novel treatment strategies to improve the survival outcomes for KIRC patients.

Tp53 as a potential therapeutic biomarker in patients with recurrent high-grade glioma treated with anlotinib and temozolomide.

e14000 Background: Patients with recurrent high-grade glioma (rHGG) had a dismal prognosis. Previous studies have found that anlotinib is effective in treating rHGG, but there are no predictive biomarkers to select potential beneficiaries. Methods: The clinical and pathological data of patients with rHGG treated with anlotinib and temozolomide (TMZ) in our hospital were collected and analyzed. Treatment response was assessed according to Response Assessment in Neuro-Oncology criteria. Survival was estimated using the Kaplan-Meier curve with the log-rank test. Tumor protein 53 ( TP53), O-6-methylguanine-DNA methyltransferase, and pre-treatment peripheral blood index were evaluated for potential therapeutic biomarkers. Results: From August 2017 to February 2022, 23 eligible patients with rHGG were included in this study. The objective response rate was 52.2% (95% confidence intervals [CI]: 30.6-73.2%), and the disease control rate was 91.3% (95% CI: 72.0-98.9%). The median progress-free survival (PFS) for all patients was 5.3 months (95% CI: 4.9-5.7 months), with a 6-month PFS rate of 30.4% (95% CI: 13.2-52.9%). The median overall survival (OS) and the 12-month OS rate were 11.0 months (95% CI: 9.7-12.3) and 39.1% (95% CI: 19.7-61.5%), respectively. Patients with TP53 wild-type had significantly higher OS than those with TP53 mutant-type (13.0 months [95% CI: 10.5-15.5 months] vs. 9.0 months [95% CI: 7.4-10.6 months], p= 0.009). Multivariate cox proportional hazards analysis showed that TP53 was an independent prognostic biomarker for OS. Conclusions: The present study showed that anlotinib combined with TMZ had a promising efficacy in treating rHGG and TP53 was a potential biomarker to predict prognosis.

MicroRNA-3692-3p is overexpressed in lung tumors but may not serve as a prognostic biomarker in lung cancer patients.

We previously reported overexpression of miR-3692-3p in the serum of non-small cell lung cancer patients. However, the expression profile and clinical utility of miR-3692-3p in the tumor tissues of lung cancer patients are not yet reported. We quantified the expression levels of miR-3692-3p in the tumors and adjacent normal lung tissues of early-stage (n = 29) and tissue biopsies of locally advanced and metastatic (n = 85) lung cancer patients using TaqMan advanced miRNA assay. We correlated miR-3692-3p expression with survival outcomes, therapeutic response, and other clinicopathological variables. We also predicted the target genes of miR-3692-3p, constructed a protein-protein interaction network, and performed functional enrichment analysis using various in silico tools. We found significant overexpression of miR-3692-3p in the tumors (Log2 fold change = 3.672; p < 0.0001) and tissue biopsies (Log2 fold change = 2.08; p = 0.0001) compared to normal lung tissues of lung cancer patients. The expression of miR-3692-3p did not correlate with overall survival (OS), progression-free survival (PFS), and response to therapy. In multivariate analysis, therapeutic response emerged as an independent prognostic biomarker of OS (HR = 3.47; p = 0.022) and PFS (HR = 19.86; p < 0.001). Our in silico analysis predicted 238 target genes of miR-3692-3p. Overexpression of miR-3692-3p could contribute to the development of lung cancer. However, mechanistic studies are warranted to shed further light on its role in lung carcinogenesis.

A Sonic Hedgehog Pathway Score to Predict the Outcome of Resected Non-Small Cell Lung Cancer Patients.

Mutations and deregulations in components of the Hedgehog (Hh) pathway have been associated with cancer onset and tumor growth in different malignancies, but their role in non-small cell lung cancer (NSCLC) remains unclear. This study aims to investigate the expression pattern of the main components of the Hh pathway in tumor and adjacent normal tissue biopsies of resected NSCLC patients. The relative expression of GLI1, PTCH1, SHH, and SMO was analyzed by quantitative polymerase chain reaction (PCR) in a cohort of 245 NSCLC patients. Results were validated in an independent cohort of NSCLC patients from The Cancer Genome Atlas (TCGA). We found that SMO and GLI1 were overexpressed in the tumor compared with normal-paired tissue, whereas PTCH1 and SHH were underexpressed. In addition, patients with higher expression levels of PTCH1 presented better outcomes. A gene expression score, called the Hedgehog Score, was calculated using a multivariable model including analyzed components of the Hh signaling pathway. NSCLC patients with a high Hedgehog Score had significantly shorter relapse-free survival (RFS) and overall survival (OS) than patients with a low score, especially at stage I of the disease. Similarly, patients in the adenocarcinoma (ADC) subcohort had shorter RFS and OS. Multivariate Cox analysis exhibited that the Hedgehog Score is an independent prognostic biomarker for OS in both the entire training cohort and the ADC subcohort. The Hedgehog Score was validated in an independent cohort of NSCLC patients from TCGA, which confirmed its prognostic value. Our results provide relevant prognostic data for NSCLC patients and support further studies on the Hh pathway.

Effector memory cytotoxic CD3+/CD8+/CD45RO+ T cells are predictive of good survival and a lower risk of recurrence in triple-negative breast cancer

Triple-negative breast cancer (TNBC) with high tumour-infiltrating lymphocytes (TILs) has been associated with a promising prognosis. To better understand the prognostic value of immune cell subtypes in TNBC, we characterised TILs and the interaction between tumour cells and immune cell subtypes. A total of 145 breast cancer tissues were stained by multiplex immunofluorescence (mIF), including panel 1 (PD-L1, PD-1, CD3, CD8, CD68 and CK) and panel 2 (Foxp3, Granzyme B, CD45RO, CD3, CD8 and CK). Phenotypes were analysed and quantified by pathologists using InForm software. We found that in the ER-negative (ER <1% and HER2-negative) group and the ER/PR-low positive (ER 1–9% and HER2-negative) group, 11.2% and 7.1% of patients were PD-L1+ by the tumour cell score, 29.0% and 28.6% were PD-L1+ by the modified immune cell score and 30.8% and 32.1% were PD-L1+ by the combined positive score. We combined ER-negative and ER/PR-low positive cases for the survival analysis since a 10% cut-off is often used in clinical practice for therapeutic purposes. The densities of PD-L1+ tumour cells (HR: 0.366, 95% CI: 0.138–0.970; p = 0.043) within the tumour compartment and CD3+ immune cells in the total area (tumour and stromal compartments combined) (HR: 0.213, 95% CI: 0.070–0.642; p = 0.006) were favourable prognostic biomarkers for overall survival (OS) in TNBC. The density of effector/memory cytotoxic T cells (CD3+CD8+CD45RO+) in the tumour compartment was an independent prognostic biomarker for OS (HR: 0.232, 95% CI: 0.086–0.628; p = 0.004) and DFS (HR: 0.183, 95% CI: 0.1301–0.744; p = 0.009) in TNBC. Interestingly, spatial data suggested that patients with a higher density of PD-L1+ tumour cells had shorter cell-cell distances from tumour cells to cytotoxic T cells (p < 0.01). In conclusion, we found that phenotyping tumour immune cells by mIF is highly informative in understanding the immune microenvironment in TNBC. PD-L1+ tumour cells, total T cells and effector/memory cytotoxic T cells are promising prognostic biomarkers in TNBC.

The prognostic value of before treatment neutrophil-to-lymphocyte ratio in nasopharyngeal carcinoma.

The aim of this analysis was to evaluate the prognostic significance of inflammatory biomarkers (NLR, dNLR, PLR and LMR) in NPC patients. This was a retrospective analysis of 111 NPC patients from January 2013 and December 2016. Receiver-operating characteristic (ROC) curve was plotted to determine the cut-off values of these inflammatory biomarkers. Univariate analysis and multivariate Cox regression model were used to evaluate the association between these parameters and progression-free survival (PFS) and overall survival (OS). The optimal critical value of NLR was 2.02, by which cases were divided into high NLR group (NLR ≥ 2.02) and low NLR group (NLR < 2.02). The elevated NLR was significantly associated with decreased OS (P = 0.009) and remained significant in multivariate analysis (HR 8.48, 95% CI 1.69-42.46, P = 0.009). The before treatment NLR may be an independent prognostic biomarker for OS in patients with NPC. NLR, dNLR and PLR might be a useful complement to TNM staging in the prognosis evaluation of NPC patients.

Positive correlation between miR-570 and prognosis of colon cancer: inhibition of cell proliferation and invasion.

Colon cancer is one of most common cancers. The progression of various cancers is driven by miRNA-570. The role of miRNA-570 in the progression of colon cancer remains unclear. We aimed to investigate the clinical function of miR-570 and its impact on colon cancer cells. We evaluated the expression of miR-570 in colon cancer cells and analyzed its influence on the various clinical parameters. The Kaplan-Meier curve was plotted to understand the clinical role of miR-570. Cox regression analysis was performed to predict the prognostic factors in colon cancer. The Cell Counting Kit-8 was used to investigate the effect of miR-570 on cell proliferation. The transwell migration assay was performed to quantify cell migration and invasion. The quantitative real-time polymerase chain reaction technique was used to analyze the sample system. The results revealed that the level of miR-570 expression in colon cancer tissues and cell lines was low. The abnormal expression of miR-570 was associated with tumor size, extent of differentiation, lymph node metastasis, and tumor-node-metastasis stages. Downregulation of miR-570 indicated poor overall survival (OS), poor relapse-free survival, and unfavorable cancer-specific survival (CSS) rates in patients with colon cancer. The results from Cox regression analysis revealed that miR-570 expression could be used as an independent prognostic biomarker for OS and CSS in colon cancer. Overexpression of miR-570 can potentially result in the inhibition of cell proliferation, migration, and invasion. The results proved that miR-570 could potentially function as a tumor suppressor and a potential prognostic factor in patients with colon cancer.

Low expression of miR-29a is associated with aggressive biology and worse survival in gastric cancer

Advanced gastric cancer (GC) is one of the most lethal cancer types, thus a better understanding of its biology in patients is urgently needed. MicroRNA (miR)-29a is a known tumor suppressive miR that is related to metastasis, but its clinical relevance in GC remains ambiguous. Here, using a large GC patient cohort we hypothesized that low expression of miR-29a in GC is associated with aggressive cancer biology and worse survival. We demonstrated that low miR-29a GC enriched cell proliferation, apoptosis, metastasis, and angiogenesis related gene sets, as well as the higher expression of related genes. Low miR-29a GC was associated with less anti-cancer immune cell infiltration as well as immune related scoring. Low miR-29a GC demonstrated a worse overall survival (OS) as well as disease specific survival (DSS) compared with high expressing miR-29a GC. Notably, low miR-29a expression was the only factor, other than residual tumor status, to be an independent prognostic biomarker of worse OS and DSS. In conclusion, low miR-29a GC was associated with aggressive cancer biology and worse OS as well as DSS. Additionally, low expression of miR-29a was an independent prognostic biomarker of OS and DSS in gastric cancer patients.

Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer.

BackgroundZinc finger protein 589 (ZNF589) is a member of the zinc finger protein (ZNF) family and plays an important role in the differentiation of haemopoietic system stem cells. However, its effects on tumorigenesis and progression have not yet been reported. The purpose of this study was to explore the prognosis and underlying mechanism of ZNF589 in breast cancer (BRCA) through a bioinformatic analysis.MethodsZNF589 transcription levels in a TCGA BC cohort were analysed and then validated using Oncomine and UALCAN. The prognostic value of ZNF589 was determined based on the overall survival (OS) and relapse-free survival (RFS) based on The Cancer Genome Atlas (TCGA) cohort and Kaplan-Meier (K-M) database. LinkedOmics and STRING were carried out to explore the potential co-expressed genes and interactive proteins as well as corresponding enrichment analysis. A Gene Set Enrichment Analysis (GSEA) was performed between two gene matrices separated by the median cut-off value of ZNF589. The methylation levels of the ZNF589 promoter were analysed using UALCAN.ResultsZNF589 was downregulated in breast tumours, and lower expression was associated with poor OS (P=0.047) and RFS (P=0.0043) according to TCGA. A subgroup analysis showed that the downregulation of ZNF589 was significantly associated with poor OS in stage 3–4 patients (P=0.0249) and progesterone receptor (PR)-negative patients (P=0.0002). Consistently, lower ZNF589 predicted poor RFS in stage 3–4 patients (P=0.0090), hormone receptor-negative patients [oestrogen receptor (ER)–, P=0.0129; PR–, P=0.0130; human epidermal growth factor receptor 2 (HER2)–, P<0.0001] and triple-negative BRCA patients (P=0.0052). Univariate and multivariate Cox regressions indicated that ZNF589 could act as an independent prognostic biomarker for OS based on age and TNM stage. Functional enrichment analysis of co-expressed genes and a protein-protein interaction (PPI) network both suggested that ZNF589 expression was negatively correlated with cell cycle progression at the transcriptional and protein-interactive levels. Finally, we found that the downregulation of ZNF589 correlated with promoter hypermethylation, and the corresponding subgroup analysis presented similar results.ConclusionsOur study highlighted that ZNF589 could act as a potential prognostic biomarker and a tumour suppressor in BRCA. A functional enrichment analysis suggested that ZNF589 may participate in multiple cancer-related pathways, including the cell cycle. Epigenetic factor promoter methylation could contribute to the downregulation of ZNF589 expression. However, deeper research about its function and underlying mechanism in cancer progression is required.

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma.

Immunotherapy has achieved efficacy for advanced colorectal cancer (CRC) patients with a mismatch-repair-deficient (dMMR) subtype. However, little immunotherapy efficacy was observed in patients with the mismatch repair-proficient (pMMR) subtype, and hence, identifying new immune therapeutic targets is imperative for those patients. In this study, transcriptome data of stage III/IV CRC patients were retrieved from the Gene Expression Omnibus database. The CIBERSORT algorithm was used to quantify immune cellular compositions, and the results revealed that M2 macrophage fractions were higher in pMMR patients as compared with those with the dMMR subtype; moreover, pMMR patients with higher M2 macrophage fractions experienced shorter overall survival (OS). Subsequently, weighted gene co-expression network analysis and protein–protein interaction network analysis identified six hub genes related to M2 macrophage infiltrations in pMMR CRC patients: CALD1, COL6A1, COL1A2, TIMP3, DCN, and SPARC. Univariate and multivariate Cox regression analyses then determined CALD1 as the independent prognostic biomarker for OS. CALD1 was upregulated specifically the in CMS4 CRC subtype, and single-sample Gene Set Enrichment Analysis (ssGSEA) revealed that CALD1 was significantly correlated with angiogenesis and TGF-β signaling gene sets enrichment scores in stage III/IV pMMR CRC samples. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm and correlation analysis revealed that CALD1 was significantly associated with multiple immune and stromal components in a tumor microenvironment. In addition, GSEA demonstrated that high expression of CALD1 was significantly correlated with antigen processing and presentation, chemokine signaling, leukocyte transendothelial migration, vascular smooth muscle contraction, cytokine–cytokine receptor interaction, cell adhesion molecules, focal adhesion, MAPK, and TGF-beta signaling pathways. Furthermore, the proliferation, invasion, and migration abilities of cancer cells were suppressed after reducing CALD1 expression in CRC cell lines. Taken together, multiple bioinformatics analyses and cell-level assays demonstrated that CALD1 could serve as a prognostic biomarker and a prospective therapeutic target for stage III/IV pMMR CRCs.

A Novel Six-Gene Signature for Prognosis Prediction in Ovarian Cancer.

Ovarian cancer (OC) is the most malignant tumor in the female reproductive tract. Although abundant molecular biomarkers have been identified, a robust and accurate gene expression signature is still essential to assist oncologists in evaluating the prognosis of OC patients. In this study, samples from 367 patients in The Cancer Genome Atlas (TCGA) database were subjected to mRNA expression profiling. Then, we used a gene set enrichment analysis (GSEA) to screen genes correlated with epithelial–mesenchymal transition (EMT) and assess their prognostic power with a Cox proportional regression model. Six genes (TGFBI, SFRP1, COL16A1, THY1, PPIB, BGN) associated with overall survival (OS) were used to construct a risk assessment model, after which the patients were divided into high-risk and low-risk groups. The six-gene signature was an independent prognostic biomarker of OS for OC patients based on the multivariate Cox regression analysis. In addition, the six-gene model was validated with samples from the Gene Expression Omnibus (GEO) database. In summary, we established a six-gene signature relevant to the prognosis of OC, which might become a therapeutic tool with clinical applications in the future.

Abstract 410: Interaction between CAFs and CD8+ T in non-small cell lung cancer (NSCLC) affects prognosis and efficacy of immunotherapy

Abstract Background: Tumor infiltrating stromal cells and immune cells are the main components of the tumor microenvironment. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and play a key role in tumor progression. Evidence indicates that CAFs are highly related to treatment response and prognosis. However, the effect of CAFs on immunotherapy response still remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The sva package was used to remove batch effects. The ssGSEA algorithm was used to assess the level of infiltration of 24 immune cells and fibroblasts from each sample. ImmuneScore was calculated using the ESTIMATE method to characterize the degree of immune infiltration. OS and DFS were analyzed using the K-M method. GO enrichment analysis is used to identify the biological process of genes. The TIDE algorithm and subclass mapping were used to predict the clinical response to immune checkpoint blockade. Results: We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples. Positive correlation between immune infiltration and CAFs infiltration through multiple methods (immune cells, Immunescore, and clustering of immune cells) (Kruskal-Wallis and Pearson test, p &amp;lt; 0.05) were found. There were only two types of immune cells in two cohorts are beneficial for prognosis, but the number of IMFRs (Immune cells / CAFs) that are positive correlated with prognosis is more than half of the total number of classes (log-rank test; P &amp;lt; 0.05). Univariate cox regression analysis showed that almost all IMFRs tended to be favorable for prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. At the best cut-off point, patients with high fibroblast content had worse prognosis (log-rank test; P &amp;lt;0.05). The prognostic performance of CD8+ T cells was not robust, but CD8+ T cells /fibroblasts (CFR) can effectively distinguish the overall survival (OS) rate of NSCLC patients [n = 1588; hazard ratio (HR), 0.66; 95% confidence interval (CI),0.56-0.78; P &amp;lt; 0.001]. and DFS rate (n = 504; HR,0.46; 95% CI, 0.34-0.62; P &amp;lt; 0.001). Multivariate analysis revealed that CFR was an independent prognostic biomarker for OS. Among the 33 independent TCGA cohorts, 29 cohorts showed a significant positive correlation between CD8 T cells and CAFs (Pearson test, P &amp;lt; 0.05). High CFR was beneficial for OS (HR, 0.72,95% CI, 0.67-0.78, P &amp;lt; 0.001). Next, we defined CFR high and CFR low groups in NSCLC, and found significant difference in OS rates between subgroups (log-rank test, P &amp;lt; 0.0001). Differential genes analysis indicate that that CFR high samples were enriched with immune activation pathways including T cell activation, cytolysis, and Antigen presentation, while CFR low was associated with immunosuppression including activation of transforming growth factor β and epithelia-mesenchymal transition. Finally, The TIDE predicted the likelihood of immunotherapy response in all NSCLC tumors. The responders had a higher CFR (Kruskal-Wallis test, P &amp;lt; 0.0001). The Submap algorithm suggested that the CFR high subgroup was more sensitive to PD-1 treatment (Bonferroni corrected, P &amp;lt; 0.01). Conclusion: The “CMIRP” we proposed shed light on a more accurate assessment of immune status. CFR is a potential marker for prognosis and predictive efficacy of immunotherapy in NSCLC. Citation Format: Xinlong Zheng, Dongqiang Zeng, Pansong Li, Wenying Pen, Xuan Gao, Zhipeng Zhou, Jing Bai, Junhui Li, Jianming Ding, Deqiang Wang, Suya Zheng, Gen Lin. Interaction between CAFs and CD8+ T in non-small cell lung cancer (NSCLC) affects prognosis and efficacy of immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 410.

Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer

BackgroundTo investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa). Patients and methodsA cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). ResultsAfter a median 34.2 (22.9–45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524–6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008–10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125–3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis. ConclusionsPreoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.

Pre-operative hypoalbuminemia is associated with complication rate and overall survival in patients with vulvar cancer undergoing surgery

ObjectiveHypoalbuminemia, a known marker for malnutrition, has been associated with an increased risk for perioperative morbidity and poor prognosis in patients with solid tumors. The aim of this study was to investigate the prognostic and predictive value of pre-treatment serum albumin levels for survival and postoperative complications in patients with vulvar cancer undergoing surgery.MethodsWithin in this retrospective study, we assessed data of 103 consecutive patients with vulvar cancer undergoing primary surgery into this study. Pre-treatment serum albumin levels were correlated with clinico-pathological parameters and complications. We performed univariate log-rank test and multivariable Cox regression models to evaluate the association between pre-treatment serum albumin and survival.ResultsWe found hypoalbuminemia (< 35 mg/dl) in 9 of 103 (8.7%) patients. No difference in tumor characteristics was observed between patients with hypoalbuminemia and normal serum albumin levels. Difference in postoperative complications (55.6% and 37.8% of patients with hypoalbuminemia and normal serum albumin levels, respectively) was not statistically significant (p = 0.345). Shorter overall survival (OS) was observed in patients with hypoalbuminemia (5-year OS rate 17.1%) when compared to patients with normal serum albumin levels (5-year OS rate 58.6%, p = 0.004). In multivariable analysis, age (p = 0.017), FIGO stage (p = 0.011) and serum albumin levels (p = 0.013) were independently associated with OS.ConclusionPre-treatment hypoalbuminemia is an independent prognostic biomarker for OS in patients with vulvar cancer. We did not find an association between pre-treatment hypoalbuminemia and a higher risk for postoperative complications.

Intratumoral IL17-producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer.

Tumor IL17-producing (IL17A+) cells infiltration has different prognostic values among various cancers. The objective of this study was to assess the effect of IL17A+ cells in gastric cancer. The study included two patient cohorts, the Cancer Genome Atlas cohort (TCGA, n = 351) and the Zhongshan Hospital cohort (ZSHC, n = 458). The TCGA and ZSHC were used for mRNA-related and cells infiltration-related analyses, respectively. The roles of IL17A mRNA and IL17A+ cells in overall survival (OS), response to adjuvant chemotherapy (ACT), and immune contexture were evaluated. Another independent cohort was included to identify the correlation between mRNA of IL17A and IL17A+ cells infiltration (the preliminary Zhongshan Hospital cohort, PZSHC, n = 21). The infiltration of IL17A+ cells was positively correlated with the expression of IL17A mRNA (Spearman's ρ = 0.811; P < 0.001). High IL17A mRNA expression and intratumoral IL17A+ cells were correlated with improved OS and remained to be significant after adjusted for confounders. Patients with TNM II/III disease whose tumor present higher intratumoral IL17A+ cells or lower peritumoral IL17A+ cells can benefit more from ACT. Elevated IL17A mRNA expression and increased intratumoral IL17A+ cells infiltration was associated with more antitumor mast cells and nature killer cells infiltration and less pro-tumor M2 macrophages infiltration. High IL17A mRNA expression represented a Th17 cells signature and immune response process and was correlated with increased cytotoxic GZMA, GZMB, IFNG, PRF1, and TNFSF11 expression. IL17A mRNA expression and intratumoral IL17A+ cells infiltration were correlated with antitumor immune contexture. IL17A+ cells infiltration could be used as an independent prognostic biomarker for OS and predictive biomarker for superior response to ACT, and further prospective validation needs to be conducted.

Gustave Roussy Immune Score Is a Prognostic Factor for Chemotherapy-Naive Pulmonary Adenocarcinoma With Wild-Type Epidermal Growth Factor Receptor.

BackgroundThe Gustave Roussy Immune Score (GRIm-Score) was developed based on the Royal Marsden Hospital (RMH) prognostic score for the purpose of a better patient selection for immunotherapy phase I trials. This scoring system is simply calculated by neutrophil-to-lymphocyte ratio, lactate dehydrogenase (LDH), and serum albumin concentration. The aim of our study was to determine whether GRIm-Score is a practically useful prognostic biomarker for advanced non-small cell lung cancer (NSCLC) patients treated with cytotoxic chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI).MethodsThis retrospective and single institutional study collected 185 adenocarcinomas without active EGFR mutation, 115 squamous cell carcinomas treated with first-line cytotoxic chemotherapy, and 140 NSCLCs with mutant EGFR treated with first- or second-generation EGFR-TKI monotherapy. These treatments were initiated between July 2007 and March 2018 at our hospital. We compared overall survival (OS) and progression-free survival (PFS) between high and low GRIm-Score groups. Using multivariate Cox proportional hazard analyses, we also found prognostic factors of survival times.ResultsThe OS and PFS of low GRIm-Score group were significantly longer than those of high-score group in wild-type EGFR adenocarcinoma (low vs. high; median OS, 18.4 vs. 5.1 months, P < 0.01, and median PFS, 5.8 vs. 3.7 months, P = 0.01) and EGFR-mutant NSCLC (median OS, 38.9 vs. 10.4 months, P < 0.01, and median PFS, 15.9 vs. 5.0 months, P < 0.01). Subsequent multivariate analyses detected high GRIm-Score in wild-type EGFR adenocarcinoma as a poor prognostic factor of OS (hazard ratio (HR) 2.20, 95% CI 1.47 - 3.31, P < 0.01), and in the EGFR-mutant NSCLC as a poor prognostic factor of PFS (HR 1.89, 95% CI 1.00 - 3.55, P = 0.049).ConclusionsHigh GRIm-Score was an independent prognostic biomarker of OS of first-line cytotoxic chemotherapy for wild-type EGFR adenocarcinoma and of PFS of first- or second-generation EGFR-TKI for EGFR-mutant NSCLC. Therefore, GRIm-Score is not only a specific selection marker for experimental immunotherapy trials, but may also be a promising and useful pretreatment prognostic maker for specific NSCLC subsets in the real-world practice.

Prognostic value of neutrophil-to-lymphocyte ratio in castration resistant prostate cancer: Single-centre study of Nigerian men.

Elevated neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a useful prognosticator of overall survival (OS) in several cancers including castration resistant prostate cancer. However, its utility in black populations known to have benign ethnic neutropenia is unknown. We evaluated the prognostic value of NLR in Nigerian men with CRPC in terms of OS. We retrospectively analysed 58 patients with castration resistant prostate cancer who received androgen deprivation therapy (ADT) and docetaxel chemotherapy at our institution. Baseline NLR was calculated from available complete blood counts. NLR cut-off point value was determined based on receiver operator characteristic (ROC) curves for mortality. A multivariate analysis was performed to investigate the association between NLR and OS. Based on the ROC curves, the NLR (AUC 0.85, 95% CI 0.74-0.97, P = 0.0001) cut-off point was determined to be 1.8. This cut-off point has a sensitivity of 92% and specificity of 70%. Median OS was 20 months (95% CI 14-27 months); the median OS in patients with NLR <1.8 and those with NLR of ≥1.8 was 40 months and 12 months respectively. Kaplan-Meier plots showed that a higher NLR of ≥1.8 correlated significantly with an increased risk of mortality, Log rank P = 0.001. Multivariate Cox regression analyses confirmed NLR as an independent prognostic biomarker for OS (HR = 1.49, 95% CI: 1.18-1.87). This study demonstrated that NLR is a useful prognostic biomarker in Nigerian men with CRPC and that elevated baseline NLR ≥1.8 is associated with poorer OS.

Prognostic Nutritional Index as an independent prognostic factor in locoregionally advanced squamous cell head and neck cancer

BackgroundLocally advanced head and neck squamous cell carcinoma (LAHNSCC) is a heterogeneous disease in which better predictive and prognostic factors are needed. Apart from TNM stage, both systemic inflammation and poor nutritional status have a negative impact on survival.MethodsWe retrospectively analysed two independent cohorts of a total of 145 patients with LAHNSCC treated with induction chemotherapy followed by concurrent chemoradiotherapy at two different academic institutions. Full clinical data, including the Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio and derived neutrophil to lymphocyte ratio, were analysed in a training cohort of 50 patients. Receiver operating characteristic curve analysis was used to establish optimal cut-off. Univariate and multivariate analyses of prognostic factors for overall survival (OS) were performed. Independent predictors of OS identified in multivariate analysis were confirmed in a validation cohort of 95 patients.ResultsIn the univariate analysis, low PNI (PNI<45) (p=0.001), large primary tumour (T4) (p=0.044) and advanced lymph node disease (N2b-N3) (p=0.025) were significantly associated with poorer OS in the validation cohort. The independent prognostic factors in the multivariate analysis for OS identified in the training cohort were dRNL (p=0.030) and PNI (p=0.042). In the validation cohort, only the PNI remained as independent prognostic factor (p=0.007).ConclusionsPNI is a readily available, independent prognostic biomarker for OS in LAHNSCC. Adding PNI to tumour staging could improve individual risk stratification of patients with LAHNSCC in future clinical trials.

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy

Background and purposeThe derived neutrophil–lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. Materials and methods258 patients were randomised to receive dCRT±cetuximab. Kaplan–Meier’s curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). ResultsAn elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29–2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17–2.29], p=0.004). Median OS was 36months (95% CI 27.8–42.4) if dNLR<2 and 18.4months (95% CI 14.1–24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. ConclusionsAn elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials.The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].

Prognostic value of lncRNA SOX2OT for Chinese cancer patients: A meta-analysis

SOX2OT has been demonstrated to be aberrantly expressed in several types of cancer and maybe serve as a prognostic marker for cancer patients. However, most individual studies have been limited by small sample sizes and controversial results. Therefore, the present meta-analysis was conducted to analyze available data to reveal the potential clinical application of SOX2OT on cancer prognosis, tumor progression, distance metastasis and lymph node metastasis. Up to February 20, 2017, literature collections were conducted by comprehensive searching electronic databases, including Cochrane Library, PubMed, Embase, BioMed Central, Springer, ScienceDirect, ISI Web of Knowledge, together with three Chinese databases: China National Knowledge Internet (CNKI), Weipu and Wanfang. The hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to assess the strength of the association. Five studies with a total of 481 cancer patients were included in the present meta-analysis. The results indicated that elevated SOX2OT significantly predicted unfavorable overall survival (OS) (HR = 2.44, 95% CI: 1.75–3.39, P<0.0001) and tumor progression (III/IV vs. I/II: HR 1.62, 95%CI: 1.30–2.02, P<0.0001), but failed to predict distant metastasis (HR: 3.30, 95%CI: 0.74–14.61, P = 0.12) and lymph node metastasis (HR: 1.29, 95% CI: 0.87–1.91, P = 0.21). The results revealed that SOX2OT expression level was an independent prognostic biomarker for OS and tumor progression in Chinese cancer patients.