Indicator Of Poor Overall Survival Research Articles

Abstract PO5-24-04: Fibronectin, DHPS and SLC3A2 Signaling Cooperate to Control Tumor Spheroid Growth, Subcellular eIF5A1/2 Distribution and CDK4/6 Inhibitor Resistance

Abstract Extracellular matrix (ECM) protein expression/deposition within and stiffening of the breast cancer (BC) microenvironment, facilitates disease progression and correlates with poor patient survival. However, the mechanisms by which ECM components control tumorigenic behaviors and responses to therapeutic intervention remain poorly understood. Fibronectin (FN) is a major ECM protein controlling multiple processes related to cancer metastasis. In this regard, we previously reported that DHPS-dependent hypusination of eIF5A1/2 is necessary for fibronectin-mediated BC metastasis and epithelial to mesenchymal transition (EMT). Here, we explored the clinical significance of an interactome generated using hypusination pathway components and markers of intratumoral heterogeneity. Solute carrier 3A2 (SLC3A2 or CD98hc) stood out as an indicator of poor overall survival among patients with basal-like BCs that express elevated levels of DHPS. We subsequently discovered that blockade or knockdown (KD) of DHPS or SLC3A2 reduced BC spheroid growth. Interestingly, spheroids stimulated with exogenous fibronectin were less sensitive to inhibition of either DHPS or SLC3A2 – an effect that could be abrogated by dual DHPS/SLC3A2 blockade or KD. In this regard, we observed that inhibition of both SLC3A2 and DHPS reduced total and hypusinated eIF5A1/2 levels most effectively. We further discovered that a subset of BC cells responded to fibronectin by increasing cytoplasmic localization of eIF5A1/2. Notably, these fibronectin-induced subcellular localization phenotypes correlated with a G0/G1 cell cycle arrest. Fibronectin-treated BC cells responded to dual DHPS/SLC3A2 blockade by shifting eIF5A1/2 localization back to a nucleus-dominant state, suppressing proliferation and further arresting cells in the G2/M phase of the cell cycle. Finally, we observed that dual DHPS/SLC3A2 inhibition increased the sensitivity of both Rb-negative and -positive BC cells to the CDK4/6 inhibitor palbociclib. Taken together, these data identify an uncharacterized mechanism through which extracellular fibronectin controls cancer cell tumorigenicity by modulating subcellular eIF5A1/2 localization. These findings provide prognostic/therapeutic utility for targeting the cooperative DHPS/SLC3A2 signaling axis to improve BC treatment responses. Citation Format: Cameron Geller, Joanna Maddela, Gabriela Ortiz-Soto, Ranel Tuplano, Farhana Runa, Yvess Adamian, Robert Güth, Luke Tomaneng, Joseph Cantor, Jonathan A. Kelber. Fibronectin, DHPS and SLC3A2 Signaling Cooperate to Control Tumor Spheroid Growth, Subcellular eIF5A1/2 Distribution and CDK4/6 Inhibitor Resistance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-04.

Abstract 7640: Prognostic significance of S100A16 expression in patients with resected lung adenocarcinoma

Abstract Background: Lung cancer is the leading cause of cancer death worldwide. Tumor recurrence is the most common cause of treatment failure after surgical resection. The S100 protein family is a multigenic group of cytoplasmic calcium-binding proteins. S100A16 has to be reported to be an independent prognostic indicator of poor overall survival in lung adenocarcinoma recently. However, the prognostic value of S100A16 in recurrence-free survival (RFS) in patients with resected lung adenocarcinoma has not been well demonstrated. The relationship between S100A16 expression and the histological subtypes of lung adenocarcinoma remained unknown. Methods: A total of 79 patients with resected lung adenocarcinoma were included in the study. S100A16 expression was determined by immunohistochemistry in tumor specimens. The prognostic value of S100A16 overexpression and its relationship with clinicopathological variables, including histology subtypes, were investigated. Results: S100A16 overexpression tended to be significantly associated with order age (P = 0.074). There was no significant association between S100A16 overexpression and predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.447). Univariate analysis indicated that pathologic stage (II or III vs. I) (P = 0.001) and S100A16 overexpression (P = 0.005) were significant prognostic factors for worse recurrence-free survival (RFS). Predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.064) tended to be a significant prognostic factor for worse RFS. In multivariate analysis, pathologic stage (II or III vs. I) (HR, 27.847; 95% CI, 4.173 to 185.831; P = 0.001), and S100A16 overexpression (HR, 21.740; 95% CI, 2.516 to 187.870; P = 0.005) were still significant prognostic factors for worse RFS. Conclusions: S100A16 overexpression was a significant prognostic factor for worse RFS in patients with resected lung adenocarcinoma. This information is useful to stratify high-risk patients of recurrence after resection of lung adenocarcinoma. Citation Format: Jung-Jyh Hung. Prognostic significance of S100A16 expression in patients with resected lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7640.

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers-DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)-XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.

Translational Control of FLT3-Mutated AML Cell Survival

Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults with a five-year survival rate of ~30%. Approximately 30% of AML patients harbor an internal tandem duplication (ITD) mutation in the FMS related receptor tyrosine kinase 3 (FLT3) gene, which is an indicator of poor overall survival and a high relapse rate. These mutations cause constitutive activation of the FLT3 receptor, which amplify proliferation and survival signaling that supports leukemia progression and chemotherapy resistance. Although FLT3 inhibitors (FLT3i) improve median survival by a couple of months, and they have reduced toxicity relative to conventional chemotherapy in clinical trials, patients eventually acquire resistance and relapse. Clinical trials have revealed that AML blasts in the bone marrow (BM) were not effectively eliminated compared to AML blasts in peripheral blood, suggesting a protective role of the BM microenvironment that counteracts FLT3i therapy. A clear understanding of FLT3-mutated AML biology and how it is influenced by the microenvironment is imperative for developing new molecular approaches for improving efficacy of FLT3i-based therapies. We have discovered that BM stromal cell mediated regulation of Ataxia Telangiectasia Mutated (ATM) promotes Mammalian Target of Rapamycin Complex 1 (mTORC1) activity despite FLT3 inhibition, which maintains translation of oxidative phosphorylation genes that are critical for AML cell survival upon treatment with FLT3i [PMID: 36259537]. Key findings show that FLT3i inhibits mTOR and mTOR-dependent translation leading to cell death. However, in the presence of BM stromal factors, survival is restored upon FLT3i by regulating ATM/mTOR-dependent translation of essential phosphorylation genes to overcome FLT3i. Moreover, we demonstrated that the combination of FLT3i and mTORC1 inhibition (mTORC1i) synergistically kills human FLT3-mutated AML cells in vitro and substantially reduces tumor burden and prevents relapse in mouse models of FLT3-mutated AML. Further studies measuring translation in FLT3-mutated AML cells revealed that there are at least two different translation pathways dictated by FLT3. One of these pathways is mTOR-dependent, as expected, and the other is mTOR-independent. Additional studies have sought to characterize FLT3-controlled translation, independent of mTOR, and its importance for FLT3-mutated AML cell survival. Although highly sensitized to FLT3i, we observed that ATM/mTOR-deficient cells maintain near-normal translation and survival. Additionally, mounting evidence suggests that there are other kinases, such as CDK1, GSK3β, and p38, that drive mTOR-independent translation by phosphorylating 4E-BP1. With this knowledge, we took an unbiased approach and used O-Propargyl Puromycin (OPP)-translation assays to assess the impact of inhibitors against these kinases on translation activity in FLT3-mutated AML cell lines. This approach revealed CDK1 as a critical regulator of translation downstream of FLT3. Interestingly, myeloid progenitors reprogram to an mTOR-independent translational program requiring phosphorylation of 4E-BP1 by CDK1 [PMID: 32386556], which could be relevant for myeloid leukemias. Further corroborating my findings, RNA sequencing data suggest that FLT3 positively regulates CDK1 expression/activity, suggesting a downstream position in parallel with mTOR. In conclusion, we have uncovered a FLT3-controlled translation pathway that promotes FLT3-mutated AML cell survival independent of mTOR. Further characterization of this pathway could help predict mechanisms of resistance to FLT3 and mTOR inhibitors in AML and could identify new targets to promote more durable remissions in patients.

Incomplete radiofrequency ablation following transarterial chemoembolization accelerates the progression of large hepatocellular carcinoma.

To examine post-operative progression and risk impact of insufficient radiofrequency ablation (RFA) following transarterial chemoembolization (TACE) for the prognosis of large hepatocellular carcinoma (HCC). From January 2014 to January 2021 were analyzed. A total of 343 patients with large HCC (diameter >5 cm) who received TACE combined with RFA were enrolled and were divided into two groups: complete ablation (CA, n = 172) and insufficient ablation (IA, n = 171). Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier curve and compared with the log-rank test. To find parameters influencing OS and PFS, clinicopathological variables underwent univariate and multivariate analysis. The cumulative 1-, 3-, and 5-year OS and PFS rates of the CA group were significantly higher than that of the IA group (P < 0.001). 25 (41%) patients in local tumor progression (LTP), 36 (59%) in intrahepatic distant recurrence (IDR), and 0 (0%) in extrahepatic distant recurrence (EDR) in the CA group. 51 (32.1%) patients in LTP, 96 (60.4%) patients in IDR, and 12 (7.5%) cases in EDR in the IA group. The recurrence patterns of the two groups were statistically significant difference (P = 0.039). In multivariate analysis, inadequate ablation and conjunction with TKIs were both significant risk factors for OS and PFS. Apart from these, older age and >7 cm of tumor size were indicators of poor OS and multiple tumors were indicators of poor PFS. Insufficient ablation causes a poor survival outcome of TACE combined with RFA for large HCC, particularly, which can promote IDR.

Chromatin Remodelling Molecule ARID1A Determines Metastatic Heterogeneity in Triple-Negative Breast Cancer by Competitively Binding to YAP.

Heterogeneity represents a pivotal factor in the therapeutic failure of triple-negative breast cancer (TNBC). In this study, we retrospectively collected and analysed clinical and pathological data from 258 patients diagnosed with TNBC at the Fudan University Cancer Hospital. Our findings show that low ARID1A expression is an independent prognostic indicator for poor overall survival (OS) and recurrence-free survival (RFS) in TNBC patients. Mechanistically, both nuclear and cytoplasmic protein analyses and immunofluorescent localisation assays confirm that ARID1A recruits the Hippo pathway effector YAP into the nucleus in human triple-negative breast cancer cells. Subsequently, we designed a YAP truncator plasmid and confirmed through co-immunoprecipitation that ARID1A can competitively bind to the WW domain of YAP, forming an ARID1A/YAP complex. Moreover, the downregulation of ARID1A promoted migration and invasion in both human triple-negative breast cancer cells and xenograft models through the Hippo/YAP signalling axis. Collectively, these findings demonstrate that ARID1A orchestrates the molecular network of YAP/EMT pathways to affect the heterogeneity in TNBC.

Preoperative lung immune prognostic index predicts survival in patients with pancreatic cancer undergoing radical resection.

Lung immune prognostic index (LIPI), a combination of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH), is currently attracting considerable interest as a potential prognostic indicator in many malignancies. Our study aimed to investigate the prognostic value of preoperative LIPI in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical resection. We retrospectively reviewed PDAC patients treated with radical resection from February 2019 to April 2021 at Chinese People's Liberation Army (PLA) general hospital. Based on the cut-off value of dNLR and LDH identified by X-tile, patients were divided into LIPI good and LIPI intermediate/poor group. Kaplan-Meier curve and log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to identify the independent prognostic value of LIPI. Subgroup analysis was performed to identify specific population benefited from radical resection. A total of 205 patients were included and the median RFS and OS was 10.8 and 24.3 months, respectively. Preoperative LIPI intermediate/poor was related to worse RFS and OS (p < 0.05). Preoperative LIPI intermediate/poor, vascular invasion and no adjuvant chemotherapy were indicators of poor OS. Patients with LIPI intermediate/poor had worse OS especially among females and those with adjuvant chemotherapy (p < 0.05). Adjuvant chemotherapy related to better RFS and OS in patients with LIPI good (p < 0.05). Preoperative LIPI intermediate/poor can be an indicator of poor prognosis in patients with PDAC undergoing radical resection. LIPI good could be an effective marker of benefit from adjuvant chemotherapy. Larger studies are warranted for further validation.

Metabolism-Related Bioinformatics Analysis Reveals That HPRT1 Facilitates the Progression of Oral Squamous Cell Carcinoma In Vitro.

Objectives Many studies have shown that dysregulation of metabolism contributes to oncogenesis. However, the exact roles of metabolism-related genes (MRGs) in oral squamous cell carcinoma (OSCC) remain unclear. Thus, we aimed to identify a prognostic signature related to MRGs in OSCC. Methods The gene sequencing data of OSCC samples and the MRG set were downloaded from The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB). The Wilcoxon rank-sum test was used to identify differentially expressed MRGs. Then, a prognostic signature was established by multivariate Cox regression analysis. Finally, prognosis-related MRGs were selected and further validated in OSCC tissues and cell lines. Results A prognostic signature that included 8 MRGs was constructed. Multiple survival analysis revealed that only HPRT1 might be an independent biomarker and indicator of poor overall survival in OSCC patients. The expression of HPRT1 was then found to be upregulated in OSCC tissues and cell lines, and suppression of HPRT1 gene expression by siRNA inhibited the proliferation, migration, and invasion of OSCC cells in vitro. Conclusions MRGs play an important role in the development of OSCC. Furthermore, HPRT1 might be an independent biomarker of OSCC and enhance OSCC proliferation, migration, and invasion in vitro; these results emphasize the potential utility of HPRT1 in OSCC therapy.

Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis

Tamoxifen (TMX) is used as adjuvant therapy for estrogen receptor-positive (ER+) breast cancer cases due to its affinity and inhibitory effects. However, about 30% of cases show drug resistance, resulting in recurrence and metastasis, the leading causes of death. A literature review can help to elucidate the main cellular processes involved in TMX resistance. A scoping review was performed to find clinical studies investigating the association of expression of molecular markers profiles with long-term outcomes in ER+ patients treated with TMX. In silico analysis was performed to assess the interrelationship among the selected markers, evaluating the joint involvement with the biological processes. Forty-five studies were selected according to the inclusion and exclusion criteria. After clustering and gene ontology analysis, 23 molecular markers were significantly associated, forming three clusters of strong correlation with cell cycle regulation, signal transduction of proliferative stimuli, and hormone response involved in morphogenesis and differentiation of mammary gland. Also, it was found that overexpression of markers in selected clusters is a significant indicator of poor overall survival. The proposed review offered a better understanding of independent data from the literature, revealing an integrative network of markers involved in cellular processes that could modulate the response of TMX. Analysis of these mechanisms and their molecular components could improve the effectiveness of TMX.

Skeletal Muscle Loss and Octogenarian Status Are Associated with S-1 Adjuvant Therapy Discontinuation and Poor Prognosis after Pancreatectomy.

Simple SummarySignificant advances in surgical techniques and perioperative care, together with adjuvant chemotherapy, have contributed to the increasing number of patients with pancreatic cancer undergoing surgery. However, the results of some studies suggest that the postoperative complications and mortality might be higher in elderly patients undergoing pancreatectomy. We aimed to identify the utility of S-1 adjuvant chemotherapy in elderly patients with resected pancreatic cancer. In our cohort of 80 patients, including 16 octogenarians, univariate and multivariate analyses revealed that S-1 adjuvant chemotherapy was associated with improved prognosis in patients with pancreatic cancer. However, we also observed that skeletal muscle loss and age of 80 years or older predicted the failure to complete adjuvant chemotherapy with S-1. We propose that evaluation of skeletal muscle mass should be considered as a useful preoperative assessment approach for determining feasibility of adjuvant chemotherapy in elderly patients.The efficacy and prognosis of adjuvant chemotherapy for resected pancreatic cancer remain unclear. We investigated the utility and risk factors of S-1 adjuvant chemotherapy in patients with pancreatic cancer undergoing pancreatectomy. This study comprised 80 patients, including 58 patients who received S-1 adjuvant chemotherapy. Skeletal muscle loss was defined using cutoff values of skeletal muscle mass index. In total, 16 (20%) octogenarian patients underwent pancreatectomy. Skeletal muscle loss was present in 56 (70%) patients. The entire course of S-1 adjuvant chemotherapy for 6 months was completed in 33 patients (41%). S-1 adjuvant chemotherapy <6 months was an independent prognostic indicator of poor overall survival. Patients who completed S-1 adjuvant chemotherapy exhibited significantly longer overall and relapse-free survival rates than those did not complete the chemotherapy (p < 0.0001 and p = 0.0003, respectively). Being an octogenarian and skeletal muscle loss were independent variables associated with the discontinuation of S-1 adjuvant chemotherapy. Finally, the S-1 adjuvant chemotherapy rates were 6.3% (1/16) and 28.6% (16/56) in octogenarian patients and those with skeletal muscle loss, respectively. S-1 adjuvant chemotherapy completion was associated with improved prognosis in patients with pancreatic cancer. Skeletal muscle loss and octogenarian status predicted the failure of S-1 adjuvant chemotherapy completion.

The outcomes of secondary AML post allogeneic hematopoietic cell transplantation significantly depend on the presence of poor-risk cytogenetic abnormalities.

Secondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy‐related AML. Large registry‐based data identified sAML as an independent poor‐outcome type of AML post allogeneic hematopoietic cell transplantation (allo‐HCT). In our study, we tried to define factors affecting outcomes of sAML post allo‐HCT, and identify patients with sAML who may truly benefit from allo‐HCT. We retrospectively analyzed the data of 64 patients aged (14‐61 years) with sAML who received allo‐HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor‐risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease‐free survival (DFS; P‐value = .009, and .004, respectively). The cumulative incidence of chronic graft‐versus‐host disease (cGVHD) was significantly lower in sAML patients with poor‐risk cytogenetics (P‐value = .003) resulting in a high risk of death without cGVHD in this group of patients (P‐value = .02). Besides, GVHD relapse‐free survival (GRFS) analysis showed that most of our studied patients experienced either relapse or debilitating grade II‐IV cGVHD in the first 2 years post allo‐HCT. We conclude that sAML patients with poor‐risk cytogenetics have a significantly lower DFS post allo‐HCT with a high risk of death without active cGVHD.

Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers.

PurposeThe predictive value of inflammatory parameters as indicators of poor overall survival (OS) has been well studied in various tumors. This study aimed to explore the association of neutrophil-lymphocyte ratio (NLR), among other parameters in upper gastro-intestinal tract tumors with distant metastases and OS.Patients and MethodsRetrospective analysis was done for 945 patients (males n= 539, 57.0%) with a median of 57 years (range 19–90 years) treated at King Hussein Cancer Center (KHCC) for gastric (n=501), pancreatic (n=355), and biliary (n=89) carcinoma. NLR, and other parameters were calculated at primary presentation, and the association between the parameters with baseline distant metastases and OS was studied. The optimal cutoff value of NLR was based on receiver operating characteristic curve (ROC) analysis. A prognostic nomogram was then constructed to explore how accurately the OS can be predicted.ResultsPatients with high baseline NLR (>3.2) had more distant metastases on presentation than patients with low NLR (≤3.2), (p-value <0.001). Age older than 57 years was associated with poor median OS (8.7 versus 10.6 months, p-value= 0.04). In addition, the location of the tumor as stomach versus biliary tract (Odds Ratio 0.443 95% CI 0.281–0.699), and pancreas versus biliary tract (Odds Ratio 1.193, 95% CI 0.749–1.902, p-value <0.001) proved to be significant. In multivariate analysis, age older than 57 years (p-value =0.0033, HR 0.792, 95% CI 0.678–0.925), location of the tumor (p-value <0.0001), presence of distant metastasis (p-value <0.0001, HR 2.063, 95% CI 1.760–2.419), and NLR (p-value <0.0001, HR 1.045, 95% CI 1.028–1.062) remained significant. Nomogram confirmed the significance of NLR as an independent prognostic factor for OS (HR = 1.62, 95% CI: 1.31–2.01, p-value <0.0001).ConclusionOur results suggested that high baseline inflammatory markers are associated with distant metastases and poor OS. The utilization of this association in management of cancer patients still warrants further investigation.

Pretreatment peripheral neutrophils, lymphocytes and monocytes predict long-term survival in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is an inflammation-related cancer, where nonresolving inflammation contributes to its development and progression. Peripheral inflammatory cells have been shown to be associated with the prognosis of various types of cancer. The present study investigated the utility of pretreatment peripheral inflammatory cells in the prognosis of patients with HCC.MethodsWe retrospectively analyzed data regarding peripheral inflammatory cell, and patient and tumor characteristics from patients with HCC who were diagnosed between November 2008 and March 2018. Baseline data, including peripheral inflammatory cell counts, were recorded before treatment. The relationships between overall survival (OS) and study variables were assessed.ResultsA total of 1681 patients who were diagnosed with HCC were included. In univariate and multivariate analyses, individual neutrophil, lymphocyte and monocyte cell counts were found as independent indicators of poor OS. High neutrophil (≥3100 × 106/L) and, monocyte (≥470 × 106/L) counts and low lymphocyte counts (< 1640 × 106/L) significantly associated with reduced OS (p < 0.05). Neutrophil and, monocyte cell counts rose and lymphocyte counts decreased in association with advancing the Barcelona Clinic Liver Cancer stage (P < 0.001).ConclusionsPretreatment peripheral neutrophils, lymphocytes, and monocytes are independently associated with outcomes of patients with HCC. These cells provides a noninvasive, low-cost, easy, and reproducible biomarker that can be used in routine clinical practice to predict the prognosis of patients with HCC.

Clinicopathological Significance of RUNX1 in Non-Small Cell Lung Cancer.

This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 (RUNX1) in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of RUNX1 in NSCLC were determined using the Infinium HumanMethylation450 BeadChip and the HumanHT-12 expression BeadChip. RUNX1 protein levels were analyzed using immunohistochemistry of formalin-fixed paraffin-embedded tissues from 409 NSCLC patients. Three CpGs (cg04228935, cg11498607, and cg05000748) in the CpG island of RUNX1 showed significantly different methylation levels (Bonferroni corrected p < 0.05) between tumor and matched normal tissues obtained from 42 NSCLC patients. Methylation levels of the CpGs in the tumor tissues were inversely related to mRNA levels of RUNX1. A logistic regression model based on cg04228935 showed the best performance in predicting NSCLCs in a test dataset (N = 28) with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.96 (95% confidence interval (CI) = 0.81–0.99). The expression of RUNX1 was reduced in 125 (31%) of 409 patients. Adenocarcinoma patients with reduced RUNX1 expression showed 1.97-fold (95% confidence interval = 1.16–3.44, p = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of RUNX1 may be a valuable biomarker for detection of NSCLC regardless of race. And, reduced RUNX1 expression may be a prognostic indicator of poor overall survival in lung adenocarcinoma.

The association between RDW and survival of patients with squamous cell carcinoma of the tongue. Simple, cheap and convenient?

The purpose of this study was to evaluate the prognostic impact of red-cell distribution width (RDW) on the overall survival (OS) of patients with squamous cell carcinoma (SCC) of the tongue. Development of cancer is connected with an ongoing inflammatory process which is reflected by laboratory indices, such as RDW that can be used as prognostic tools. The study group consists of 74 consecutive patients treated with radical radiotherapy or chemo-radiotherapy for SSC of the tongue at one institution between 2005-2014. RDW was assessed based on routine blood tests done before the start of the treatment. ROC curve was applied to assess value of RDW in prediction of OS, and a cut-off value for further tests was obtained using the Younden index. The survival analysis was performed using the Kaplan-Meier method, log-rank testing and Cox regression model. The AUC for RDW in ROC analysis was 0.703, and the optimal cut-off value was 13.5%. 5-year OS was significantly lower in patients with RDW ≥ 13.5% compared with patients with RDW < 13.5% (67% vs. 26%, p-value = 0.0005). Additionally, high RDW was associated with a greater odds ratio for 5-year OS in a multivariate Cox proportional hazards regression analysis (3.43, 1.62-7.25; p = 0.001). Our study demonstrated that pre-treatment RDW ≥ 13,5% is an indicator of poor overall survival in patients with SCC of the tongue. Since RDW is a cheap and convenient marker, usually routinely assessed during complete blood count tests, it could be further used as an additional prognostic tool in patients with tongue cancers.

Acute kidney injury after nephron sparing surgery and microwave ablation: focus on incidence, survival impact and prediction

Purpose To compare acute kidney injury (AKI) incidence between nephron sparing surgery (NSS) and microwave ablation (MWA) for T1a RCC patients, reveal the effect of AKI on survival prognosis, construct AKI nomogram and use Law of Total Probability for survival probability (SP) prediction. Materials and methods Patients were studied retrospectively after NSS (n = 1267) or MWA (n = 210) from January 1, 2011 to June 30, 2017. Using one to one Propensity Score Matching (PSM), 158 pairs of patients were identified for the cohort study. AKI incidence, risk factors and impact on survival outcomes were analyzed using Chi-square test, logistic and cox regression analysis. AKI risk and SP were predicted by nomogram and Law of Total Probability. The performance of the nomogram was assessed with respect to its discrimination, calibration, and clinical usefulness. Results AKI occurred more commonly in NSS (27.85%) cohort, when compared to MWA (17.72%) cohort (p = 0.032), but treatment modality was not independently predictive of AKI occurrence (odds ratio [OR]: 0.598; 95% confidence interval [CI]: 0.282–1.265; p = 0.178). The 5-yr overall survival (OS) was lower in AKI patients (73.5%) compared with non-AKI patients (94.8%; p < 0.001). AKI was an independent risk factor for all-cause mortality in RCC patients (hazard ratio [HR]: 2.820; 95% confidence interval [CI]: 1.110–7.165; p = 0.029). Predictors for both NSS- and MWA-related AKI included tumor diameter, baseline eGFR and CCI score. RENAL score and tumor blood supply can predict AKI after NSS and MWA, respectively. The AKI normograms demonstrated good discrimination, with AUCs >0.86, excellent calibration and net benefits at the decision curve analysis with probabilities ≥5%. SP predicted by Law of Total Probability was comparable to actual OS. Conclusion AKI was an early indicator for poor overall survival in RCC patients. It can be predicted by several oncological parameters. Nomogram and Law of Total Probability can accurately predict AKI risk and SP.

Verification of inflammation-based prognostic marker as a prognostic indicator in hepatocellular carcinoma.

AimAlthough inflammation‐based markers in cancer have been used for prognostic prediction, the most useful marker for hepatocellular carcinoma (HCC) has not been established. We investigated the usefulness of various inflammation‐based markers in HCC patients after hepatectomy.MethodsA total of 478 patients who underwent initial hepatectomy for HCC from 2009 to 2015 and were diagnosed with pathological HCC were included in this retrospective study. Inflammation‐based markers consisted of the C‐reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, platelet to lymphocyte ratio and prognostic index. Univariate and multivariate analyses for overall survival (OS) and disease‐free survival (DFS) using the Cox proportional hazard model were carried out. Kaplan‐Meier analysis and log‐rank test were used for comparison of OS and DFS. To reduce influences of selection bias and confounders for stratifying CAR, clinicopathological characteristics of patients were balanced by propensity score matching.ResultsMultivariate analysis identified only high CAR (>0.027) as an indicator of poor OS, and high CAR and high GPS (1‐2) as indicators of poor DFS among inflammation‐based markers. After propensity score matching, 124 patients each with low CAR and high CAR were matched. High CAR was correlated with both poor OS and DFS.ConclusionC‐reactive protein to albumin ratio was the most valuable prognostic indicator after hepatectomy for HCC among inflammation‐based markers.

Prognostic Significance of 18F-FDG PET/CT Metabolic Parameters and Tumor Galectin-1 Expression in Patients With Surgically Resected Lung Adenocarcinoma

PurposeTo study the prognostic significance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) metabolic parameters and tumor galectin-1 (Gal-1) expression in patients surgically treated for lung adenocarcinoma. Patients and MethodsThe medical records of 96 patients with primary lung adenocarcinoma who underwent surgery after 18F-FDG PET/CT were retrospectively reviewed. The maximal standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis of the primary tumor were measured through PET/CT imaging. The expression of tumor Gal-1, glucose transporter 1 (GLUT-1), and hexokinase II (HK-II) were examined through immunohistochemistry. ResultsThere were significant positive correlations between tumor Gal-1 and SUVmax, tumor Gal-1 and metabolic tumor volume, tumor Gal-1 and total lesion glycolysis, tumor Gal-1 and GLUT-1 expression, tumor Gal-1 and HK-II expression, and SUVmax and tumor GLUT-1 and HK-II expression (P < .0001 in all cases). SUVmax was the only independent predictor of tumor Gal-1 expression. On receiver operating characteristic analysis, the optimal cutoff value of SUVmax for predicting tumor Gal-1 expression was 5.1. Progression-free and overall survival were significantly shorter in patients with Gal-1–positive tumors than in those with Gal-1–negative tumors (P ≤ .001). On multivariate analysis, advanced tumor stage (P = .001) and tumor Gal-1 expression (P < .0001) were independent prognostic indicators of poor progression-free survival, while advanced tumor stage (P < .0001) and SUVmax (P = .024) were independent prognostic indicators of poor overall survival. Conclusion18F-FDG PET/CT has the potential to be used as a noninvasive imaging modality to assess tumor Gal-1 status and prognosis in lung adenocarcinoma.

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients

BackgroundThe expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC).MethodsThere were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients’ clinical characteristics, and clinical results.ResultsB4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression.ConclusionsOur evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

Increased DHRS12 expression independently predicts poor survival in patients with high-grade serous ovarian cancer.

To explore the expression profile of some DHRS genes in high-grade serous ovarian cancer (SOVC) and to study their prognostic values. A retrospective bioinformatic analysis was performed using data in the Gene Expression Omnibus, the Human Protein Atlas and the Cancer Genome Atlas-Ovarian Cancer. Increased DHRS12 expression was an independent indicator of poor overall survival (hazard ratio [HR]: 1.265, 95% CI: 1.075-1.488; p =0.005) and recurrence-free survival (RFS; HR: 2.242, 95%CI: 1.464-3.432; p<0.001) in patients with high-grade SOVC. DNA deletion was associated with decreased DHRS12 expression, as well as the best overall survival and RFS among the three copy number alteration groups. DHRS12 might serve as a valuable prognostic biomarker in high-grade SOVC.