Reliable Prognostic Indicator Research Articles

Astragaloside IV Inhibits the Proliferation of Human Uterine Leiomyomas by Targeting IDO1.

Simple SummaryImmunotherapy is increasingly becoming a success strategy for oncology treatment. Indoleamine-2,3-dioxygenase1 (IDO1) is a tryptophan-degrading enzyme involved in immunological escape mechanisms, which is considered as a potential target for tumor therapy. However, the clinical efficacy of IDO1 inhibitors is not promising. Therefore, there is an urgent to investigate the mechanism between chemical drugs with antitumor effects and IDO1-mediated immunosuppression. The Chinese medicine AS-IV exerts antitumor effects with many advantages, including fewer toxic side effects and immunomodulatory effects. We noted the lack of studies of AS-IV on benign tumors. Therefore, our study demonstrates the Inhibitory effect of AS-IV on ULMs and elucidates the underlying mechanism.Astragaloside IV (AS-IV) is a chemical found in traditional Chinese medicine called Astragalus membranaceus (Fisch.) Bunge that has antitumor properties. However, the roles and mechanisms of AS-IV in uterine leiomyomas (ULMs) are unclear. The immunosuppressive enzyme indoleamine-2,3-dioxygenase-1 (IDO1) is involved in tumor formation. IDO1 is a new and reliable prognostic indicator for several cancers. In this work, AS-IV was applied to ULM cells in various concentrations. CCK-8, immunofluorescence, and flow cytometry were used to examine the proliferation and apoptosis of ULM cells caused by AS-IV. After lentiviral vector transduction with IDO1 short hairpin RNA (shRNA), the knockdown and overexpression of IDO1 were stable in ULM cells. To verify the antitumor effect of AS-IV in vivo, we established a rat model of uterine leiomyoma. HE staining, Masson staining, and transmission electron microscopy were used to observe pathological changes in the uterus, and the levels of serum sex hormones were measured by radio immune assay (RIA). The levels of CD3+T, CD4+T, and CD25+ Foxp3+Treg in rat peripheral blood were detected by flow cytometry. Western blotting and immunohistochemistry were used to examine protein expression. We found that AS-IV dramatically increased the apoptotic rate of ULM cells and reduced viability in a time- and dosage-dependent manner. After sh-IDO1 lentiviral transfection, we discovered that knocking down IDO1 reversed the effects of AS-IV on ULM cell proliferation and autophagy. We also found that AS-IV can effectively inhibit the growth of ULMs in vivo. AS-IV may promote apoptosis and autophagy in ULMs by activating PTEN/PI3K/AKT signaling through inhibition of IDO1. These findings imply that AS-IV exerts antifibroid effects, and the underlying mechanism may be IDO1, which is involved in proliferation, apoptosis, and autophagy.

Integration of OV6 expression and CD68+ tumor-associated macrophages with clinical features better predicts the prognosis of patients with hepatocellular carcinoma

Background: Reliable prognostic indicators for accurately predicting postoperative outcomes in Hepatocellular carcinoma (HCC) patients are lacking. Although cancer stem-like cells (CSCs) and tumor-associated macrophages (TAMs) in tumor microenvironment are implicated in the occurrence and development of HCC, whether the combination of CSC biomarkers and TAM populations could achieve better performance in predicting the prognosis of patients with HCC has been rarely reported.Methods: A total of 306 HCC patients were randomly divided into the training and validation cohorts at a 1:1 ratio, and the expression of OV6 and CD68 was assessed using immunohistochemistry in HCC samples. The prognostic value of these biomarkers for post-surgical survival and recurrence were evaluated by the curve of receiver operating characteristic and multivariate Cox regression analyses.Results: The density of OV6+ CSCs was positively correlated with the infiltration of CD68+ TAMs in HCC. Both high OV6 expression and CD68+ TAM infiltration was closely associated with poor overall survival (OS) and progression-free survival (PFS) of HCC patients. Moreover, overexpression of OV6 and infiltration of CD68+ TAMs were identified as independent prognostic factors for OS and PFS after liver resection. The integration of OV6 and CD68 with tumor size and microvascular invasion exhibited highest C-index value for survival predictivity in HCC patients than any other biomarkers or clinical indicators alone.Conclusion: Incorporating intratumoral OV6 expression and CD68+ TAMs infiltration with established clinical indicators may serve as a promising prognostic signature for HCC, and could more accurately predict the clinical outcomes for HCC patients after liver resection.

Preoperative Naples prognostic score is a reliable prognostic indicator for newly diagnosed glioblastoma patients.

BackgroundGlioblastoma (GBM) accounts for approximately 80% of malignant gliomas and is characterized by considerable cellularity and mitotic activity, vascular proliferation, and necrosis. Naples prognostic score (NPS), based on inflammatory markers and nutritional status, has a prognostic ability in various cancers. In the current study, we aim to explore the prognostic value of operative NPS in GBM patients and compare the prognostic ability between NPS and controlling nutritional status (CONUT).Materials and methodsThe retrospective analysis was carried out on consecutive newly diagnosed GBM patients who had underwent tumor resection at West China Hospital from February 2016 to March 2019. All statistical analyses were conducted using SPSS software and R software.ResultsA total of 276 newly diagnosed GBM patients were enrolled in the current study. Overall survival (OS) (p < 0.001) and tumor location (p = 0.007) were significantly related to NPS. Serum albumin concentrate, cholesterol concentrate, neutrophil-to-lymphocyte ratio, lymphocyte ratio, and CONUT score were all significantly associated with NPS (p < 0.001). The Kaplan–Meier curve indicated that NPS (log-rank test, p < 0.001) and CONUT score (log-rank test, p = 0.023) were significantly associated with OS. Multivariate Cox regression revealed that both NPS and CONUT score served as independent prognostic indicators. The prognostic model with NPS had the strongest prognostic capability and best model-fitting.ConclusionIn the current study, NPS is found as an independent prognostic indicator for patients with newly diagnosed GBM, and the prognostic ability of NPS is superior to CONUT score.

Assessing the Prognostic Capability of Immune-Related Gene Scoring Systems in Lung Adenocarcinoma.

Background Lung adenocarcinoma (LUAD) is the commonest of the subtypes of lung cancer histologically. For this study, we intended to analyze the expression profiling of the immune-related genes (IRGs) from an independently available public database and developed a potent signature predictive of patients' prognosis. Methods Gene expression profiles and the clinical data of lung adenocarcinoma were gathered from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), and the obtained data were split into a training set (n = 226), test set (n = 83), and validation set (n = 400). IRGs were then gathered from the ImmPort database. A prognostic model was constructed by analyzing the training set. Then the GO and KEGG analysis was performed, and a gene correlation prognostic nomogram was constructed. Finally, external validation, such as immune infiltration and immunohistochemistry, was performed. Results The 110 genes were significant by univariate Cox regression analysis and randomized survival forest algorithm for the training set and showed a good distinction between the low-risk-score and high-risk-score groups in the training set (P < 0.0001) by screening for four prognosis-related genes (HMOX1, ARRB1, ADM, PDIA3) and validated by the test set GSE30219 (P=0.0025) and TCGA dataset (P=0.00059). Multivariate Cox showed that the four gene signatures were an individual risk factor for LUAD. In addition, the genes in the signatures were externally verified using an online database. In particular, PDIA3 and HMOX1 are essential genes in the prognostic nomogram and play an important role in the model of immune-related genes. Conclusion Four immune-related genetic signatures are reliable prognostic indicators for patients with LUAD, providing a relevant theoretical basis and therapeutic rationale for immunotherapy.

CK2α as a prognostic factor in invasive ductal carcinomas of the breast: cancer recurrence prognosis by surgical sampling

Breast cancer is the most common cancer in Japanese and Asian women. Although the 5-year survival rate of these patients is relatively high, recurrences and fatalities do occur. The objective of this work was to develop a reliable prognostic indicator to guide therapeutic intervention without waiting for recurrence or metastasis. We have previously shown that positive immunohistochemical staining of a protein kinase, CK2α (CSNK2A1), in nucleoli of invasive ductal carcinoma cells is strongly associated with tumour recurrence and poor patient outcomes. For this study, we did an immunohistochemistry investigation of the location of CK2α in the nuclei and nucleoli of formalin-fixed, paraffin-embedded tissue block samples from patients with invasive ductal carcinoma who underwent surgery in 2008-14 but no neoadjuvant chemotherapy at Hoshi General Hospital, Fukushima, Japan. Furthermore, a new study with 59 patients with luminal type breast cancer was done. Patients were followed-up (clinicopathological information and outcomes) for more than 5 years. To characterise CK2α-associated proteins systematically, nuclear and nucleolar extracts were prepared from MCF-7 cells and immunoprecipitated with anti-CK2α antibodies followed by nano-flow liquid chromatography mass spectrometry analysis. We did a Kaplan-Meier analysis to evaluate whether nucleolar CK2 staining might be associated with poor recurrence-free survival. This retrospective study was approved by the Institutional Review Boards of Fukushima Medical University and Hoshi General Hospital. Samples from 112 patients were included. 105 (94%) of 112 patients with invasive ductal carcinoma had high CK2α expression in nuclei, and 41 (37%) of 112 displayed it predominantly in nucleoli. Clinical and pathological malignancy was strongly correlated with high nuclear and nucleolar CK2α expression. Recurrence-free survival was significantly reduced in patients with positive nucleolar CK2α staining (n=41; median 7·89 years [IQR 4·86-8·86]), comparing with patients with negative nucleolar staining (n=71; median 8·89 years [7·87-9·79]; p<0·0001). Kaplan-Meier analysis showed a decrease of approximately 50% in recurrence-free survival in patients with nucleolar CK2α-positive stain in the triple-negative breast cancer (p=0·0069) and post-operative stage 3 (p=0·0073) groups. By contrast, no patients who relapsed or died in the triple-negative breast cancer group had negative staining for nucleolar CK2α. Evaluation of nucleolar CK2α can be considered as an independent prognostic factor because it reached significance in multivariate analysis (hazard ratio [HR] 5·26 [95% CI 1·35-20·55]; p=0·017). In addition, the HR of nucleolar CK2α-positive staining was less affected by adjustments in Cox proportional multivariate analysis. Cluster analysis showed that nucleolar CK2α-positive staining contributed more than any other clinicopathological factor to predicting the variation in the future length of survival. Analysis with luminal type breast cancer (n=59), in which the risk of recurrence is generally low and which is treated postoperatively with hormone therapy alone, showed that cancer recurrence and poor patient outcomes strongly associate with nucleolar CK2α-positive stain (n=7; p=0·037) by Kaplan-Meier analysis. In this case, nucleolar CK2α is considered a sole independent prognostic factor (HR 2·11 [95% CI 0·27-3·69]; p=0·0087). Evaluation of this method in other solid tumours is ongoing. Our results suggest that the evaluation of nucleolar CK2α-positive staining might be a new and independent prognostic factor that can improve treatment efficacy and patient quality of life after surgical resection of the tumour. The application of this analysis could contribute to early treatment strategy decisions and to companion diagnostics. The protein interactome of nuclear CK2 complexes showed CK2α's role in protein synthesis and RNA post-transcriptional modification. Specifically, a more detailed evaluation of CK2α function in nucleolar events in malignant cells might lead to the development of novel, more accurately targeted anti-cancer therapeutics. In conclusion, evaluating nucleolar CK2α staining in combination with other clinicopathological indicators might allow for a more accurate prediction of future recurrence or metastasis, which cannot be accomplished by current methods. Japan Agency for Medical Research and Development (grant number 20lm0203006j0004).

Frequency and Consequences of Lymphocele Formation After Extended Lymphdissection in Patients Undergoing Open Retropubic Prostatectomy

It is known that any surgery can lead to the risk of development of the late postoperative complication – lymphocele, which can occur in a period from about 2 weeks to 6 months after surgery. The objective: to analyze the frequency of lymphocele formation and its outcomes after open retropubic prostatectomy (ORP) and extended lymph node dissection (ELND) in patients with localized prostate cancer (PC). Materials and methods. The study included patients after ORP and ELND who were observed after operation for a period more than 6 months. All operations were performed by the retropubic extraperitoneal access by one surgeon. All patients received low molecular weight heparins to prevent thromboembolic complications. In the postoperative period, patients had control ultrasound examination (USE), the frequency and outcomes of lymphocele were studied retrospectively. If the results of USE were normal, no imaging study was performed for the next 6 months. Results. The results of treatment of patients with localized PC were analyzed. The mean observe period was 16.2 months. Lymphocele developed in 4% of cases and was symptomatic in 1.5 % of men. In all patients, lymphocele was detected within 1 month after surgery. In 74% of cases, lymphocele regressed within 3 months after surgery according to results of USE. In 64% of patients with lymphocele more 3 months the symptoms associated with cystic infection that required adequate drainage developed. Patients with diabetes had a higher risk of infected lymphocele development. Other symptoms which were associated with lymphocele have been found rarely. Comparison of preoperative characteristics of the patients with and without lymphocele did not demonstrate reliable prognostic indicators of possible lymphocele formation in a retrospective analysis of these persons. Conclusions. The risk of the development of symptomatic lymphocele after open retropubic prostatectomy and extended lymph node dissection is quite rare. However, ultrasound examination for 3 months after surgery is considered appropriate. It is recommended to perform the percutaneous drainage of the pathological cavity under ultrasound control in case of the detection of symptomatic lymphocele, because this procedure is safe and effective.

Development of a Prognostic Alternative Splicing Signature Associated With Tumor Microenvironment Immune Profiles in Lung Adenocarcinoma

BackgroundAlternative splicing (AS), a pivotal post-transcriptional process across more than 95% of human transcripts, is involved in transcript structural variations and protein complexity. Clinical implications of AS events and their interaction with tumor immunity were systematically analyzed in lung adenocarcinoma (LUAD).MethodsTranscriptome profiling as well as AS data of LUAD were retrospectively curated. Then, the network of the overall survival (OS)-relevant AS events with splicing factors was established. After screening OS-relevant AS events, a LASSO prognostic model was conducted and evaluated with ROC curves. A nomogram that integrated independent prognostic indicators was created. Immune response and immune cell infiltration were estimated with ESTIMATE, CIBERSORT, and ssGSEA algorithms. Drug sensitivity was inferred with pRRophetic package.ResultsIn total, 2415 OS-relevant AS events were identified across LUAD patients. The interaction network of splicing factors with OS-relevant AS events uncovered the underlying regulatory mechanisms of AS events in LUAD. Thereafter, a prognostic model containing 12 AS events was developed, which acted as a reliable and independent prognostic indicator following verification. A nomogram that constituted stage and risk score displayed great effectiveness in evaluating the survival likelihood. Moreover, the AS-based prognostic model was in relation to immune response and immune cell infiltration. Patients with a high-risk score displayed therapeutic superiority to cisplatin, erlotinib, gefitinib, and gemcitabine. Finally, three AS-relevant genes (CDKN2A, TTC39C, and PKIB) were identified as prognostic markers.ConclusionCollectively, our findings developed an AS event signature with powerful prognostic predictive efficacy in LUAD.

A Novel lncRNA Panel for Risk Stratification and Immune Landscape in Breast Cancer Patients

PurposeIn recent years, breast cancer (BC) has been a primary cause of mortality in women. However, the underlying mechanisms remain to be elucidated. Accumulating evidence has supported the hypothesis that long noncoding RNAs (lncRNAs) play central roles in the progression of cancer. We aimed to construct an immune-related lncRNA panel to predict the prognosis of patients with BC and evaluate the immune features.MethodsThe expression profiles of patients with BC were obtained from The Cancer Genome Atlas (TCGA) database to screen the differentially expressed lncRNAs (DELs). Pearson’s correlation analysis was employed to filter the DELs related to the immune-associated genes. Univariate Cox regression, the LASSO algorithm, and multivariate Cox regression analyses were conducted to establish the model. Functional enrichment analyses and biological experiments were performed to explore the immune activity of the lncRNA panel.ResultsA four-immune-related lncRNA panel (IRLP) composed of AC022196.1, ARHGAP26-AS1, DPYD-AS1 and PURPL was established in TCGA training cohort. The prognostic accuracy of the predictive model was confirmed in TCGA internal validation cohort, TCGA entire cohort and Qilu external validation cohort. Bioinformatics analyses indicated that the IRLP had a close relationship with tumour infiltrating immune cells and immunomodulatory biomarkers. The biological functions of the four immune-related lncRNAs in BC were first investigated in vitro and in vivo. PURPL was indicated to play a central role in the regulation of macrophage recruitment and polarization via CCL2.ConclusionOur study identified IRLP as a reliable prognostic indicator with great potential for clinical application in personalized immunotherapy.

The role of preoperative systemic immune-inflammation index in predicting the prognosis of patients with digestive tract cancers: A meta-analysis

BackgroundSystemic immune-inflammation index (SII) is correlated with prognosis in several types of cancers. In this study, we conducted a meta-analysis to systematically evaluate the prognostic significance of SII in digestive tract cancers. MethodsPubMed, Web of Science, Embase and Cochrane databases were searched for articles reporting an association between preoperative SII and the survival of patients with digestive tract cancers. The baseline information was extracted, with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS) as outcome indicators. The hazard ratio (HR) was used to calculate the relationship between SII and patient survival. ResultsOn the basis of specified inclusion and exclusion criteria, a total of 17 eligible studies covering 8384 patients were included in this meta-analysis. The meta-analysis showed that high preoperative SII was associated with low OS (HR = 1.86, 95% confidence interval [CI] = 1.57–2.21) and DFS (HR = 2.03, 95% CI = 1.63–2.52) in patients with digestive tract cancers. Subgroup analysis indicated that higher SII was consistently associated with lower OS regardless of geographic region, sample size, disease type, or SII thresholds. ConclusionsSystemic immune-inflammation index can act as a reliable prognostic indicator in patients with digestive tract cancers.

Prognostic value of pre-treatment advanced lung cancer inflammation index in non-small cell lung cancer: a meta-analysis

Purpose To identify the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in non-small cell lung cancer (NSCLC) including surgical patients who were diagnosed with early stage. Methods The PubMed, EMBASE and Web of Science electronic databases were searched up to January 12, 2022 for relevant studies. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association between pre-treatment ALI and overall survival (OS) or progression-free survival (PFS) of NSCLC patients. All statistical analyses were conducted by STATA 12.0 software. Results A total of 14 studies involving 3607 participants were included. The pooled results indicated that lower pre-treatment ALI was significantly related to poorer OS (HR = 2.20, 95% CI: 1.46–3.33, P < 0.001) and PFS (HR = 1.78, 95% CI: 1.49–2.13, P < 0.001). Besides, subgroup analysis also demonstrated that lower pre-treatment ALI was associated with worse OS in surgical (P < 0.001) and non-metastatic (P < 0.001) patients and worse PFS of surgical (P < 0.001) NSCLC patients. Conclusion Pre-treatment ALI was a novel and reliable prognostic indicator in NSCLC and lower pre-treatment ALI predicted worse survival including patients diagnosed with early stage. However, more prospective high-quality studies are still needed to verify the above findings.

Prognostic value of YKL-40 in colorectal carcinoma patients: A meta-analysis.

BACKGROUNDIn recent years, the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated. However, whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified. AIMTo identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients. METHODSSeveral electronic databases including the PubMed, EMBASE, Web of Science, CNKI, VIP and WanFang were searched for relevant studies. The hazard ratios (HR) and 95% confidence intervals (CI) were combined and the primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. All statistical analysis were conducted by STATA 15.0 software. RESULTSA total of nine studies involving 2545 patients were included. The pooled results indicated that YKL-40 was significantly associated with poor OS (HR = 1.80, 95%CI: 1.32-2.45, P < 0.001) and PFS (HR = 1.62, 95%CI: 1.22-2.16, P = 0.001). Subgroup analysis stratified by the treatment, tumor type and source of YKL-40 showed similar results.CONCLUSIONElevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients. YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.

Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio for EGFR-Mutated Advanced Non-Small-Cell Lung Cancer Patients Treated with First-Line EGFR-TKIs: A Large Population-Based Study and Literature Review.

BackgroundResistance inevitably develops in epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients after treatment of EGFR tyrosine kinase inhibitors (EGFR-TKIs). The albumin-to-alkaline phosphatase ratio (AAPR), a novel index, has been reported to be associated with survival in various cancers. In this study, we explored the prognostic value of AAPR in EGFR-mutated advanced NSCLC patients treated with first-line EGFR-TKIs.MethodsThe clinical and pretreatment laboratory data were retrospectively extracted from hospital medical system. The Log-rank and Kaplan–Meier analyses were adopted to detect differences in survival between groups. Univariate and multivariate Cox’s proportional hazard regression models were applied to assess the prognostic value of AAPR for progression-free survival (PFS) and overall survival (OS).ResultsTotally, 598 EGFR-mutated NSCLC patients with stage IIIB-IV were enrolled into this study. The median age of all patients was 60 years, and 56.9% were women. About 97% patients had common EGFR gene mutations of deletions in exon 19 (19 del) or a point mutation in exon 21 (L858R). Using receiver operating characteristic (ROC) curve analysis and the Youden index, the optimal cut-off value of pretreatment AAPR was 0.47. Patients with high AAPR achieved longer median PFS and OS than patients with low AAPR (14.0 months vs 10.4 months, P<0.01; 58.2 months vs 36.7 months, P<0.001, respectively). The multivariate analysis by Cox’s proportional hazards regression model demonstrated that AAPR was an independent prognostic factor for both PFS (HR: 0.813, 95% CI: 0.673–0.984, P=0.033) and OS (HR: 0.629, 95% CI: 0.476–0.830, P=0.001).ConclusionPretreatment AAPR, measured as part of routine blood biochemical test, may be a reliable prognostic indicator in EGFR-mutated advanced NSCLC patients treated with first-line first-generation EGFR-TKIs.

Impaired cognitive control in patients with brain tumors

Though the assessment of cognitive functions is proven to be a reliable prognostic indicator in patients with brain tumors, some of these functions, such as cognitive control, are still rarely investigated. The objective of this study was to examine proactive and reactive control functions in patients with focal brain tumors and to identify lesioned brain areas more at “risk” for developing impairment of these functions. To this end, a group of twenty-two patients, candidate to surgery, were tested with an AX-CPT task and a Stroop task, along with a clinical neuropsychological assessment, and their performance was compared to that of a well-matched healthy control group. Although overall accuracy and response times were similar for patients and control groups, the patient group failed more on the BX trials of the AX-CPT task and on the incongruent trials of the Stroop task, specifically. Behavioral results were associated with the damaged brain areas, mostly distributed in right frontal regions, by means of a lesion-symptom mapping multivariate approach. This analysis showed that a white matter cluster in the right prefrontal area was associated with lower d’-context values on the AX-CPT, which reflected the fact that these patients rely more on later information (reactive processes) to respond to unexpected and conflicting stimuli, than on earlier contextual cues (proactive processes). Taken together, these results suggest that patients with brain tumors present an imbalance between proactive and reactive control strategies in high interfering conditions, in association with right prefrontal white matter lesions.

Prognostic Value of Glasgow Prognostic Score in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Systemic inflammation is a key factor in tumor growth. The Glasgow Prognostic Score (GPS) has a certain value in predicting the prognosis of lung cancer. However, these results still do not have a unified direction. Methods: A systematic review and meta-analysis were performed to investigate the relationship between GPS and the prognosis of patients with non-small cell lung cancer (NSCLC). We set patients as follows: GPS = 0 vs. GPS = 1 or 2, GPS = 0 vs. GPS = 1, GPS = 0 vs. GPS = 2. We collected the hazard ratio (HR) and the 95% confidence interval (CI). Results: A total of 21 studies were included, involving 7333 patients. We observed a significant correlation with GPS and poor OS in NSCLC patients (HRGPS=0 vs. GPS=1 or 2 = 1.62, 95% CI: 1.27–2.07, p ≤ .001; HRGPS=0 vs GPS=1 = 2.14, 95% CI:1.31–3.49, p ≤ .001; HRGPS=0 vs. GPS=2 = 2.64, 95% CI: 1.45–4.82, p ≤ .001). Moreover, we made a subgroup analysis of surgery and stage. The results showed that when divided into GPS = 0 group and GPS = 1 or 2 group, the effect of high GPS on OS was more obvious in surgery (HR = 1.79, 95% CI: 1.08–2.97, p = .024). When GPS was divided into two groups (GPS = 0 and GPS = 1 or 2), the III-IV stage, higher GPS is associated with poor OS (HR = 1.73, 95% CI: 1.43–2.09, p ≤ .001). In the comparison of GPS = 0 and GPS = 1 group (HR = 1.56, 95% CI: 1.05–2.31, p = .026) and the grouping of GPS = 0 and GPS = 2(HR = 2.23, 95% CI: 1.17–4.26, p = .015), we came to the same conclusion. Conclusion: For patients with NSCLC, higher GPS is associated with poor prognosis, and GPS may be a reliable prognostic indicator. The decrease of GPS after pretreatment may be an effective way to improve the prognosis of NSCLC.

Construction and Verification of a Combined Hypoxia and Immune Index for Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive malignancies in humans. Hypoxia-related genes are now recognized as a reflection of poor prognosis in cancer patients with cancer. Meanwhile, immune-related genes play an important role in the occurrence and progression of ccRCC. Nevertheless, reliable prognostic indicators based on hypoxia and immune status have not been well established in ccRCC. The aims of this study were to develop a new gene signature model using bioinformatics and open databases and to validate its prognostic value in ccRCC. The data used for the model structure can be accessed from The Cancer Genome Atlas database. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the hypoxia- and immune-related genes associated with prognostic risk, which were used to develop a characteristic model of prognostic risk. Kaplan-Meier and receiver-operating characteristic curve analyses were performed as well as independent prognostic factor analyses and correlation analyses of clinical characteristics in both the training and validation cohorts. In addition, differences in tumor immune cell infiltrates were compared between the high and low risk groups. Overall, 30 hypoxia- and immune-related genes were identified, and five hypoxia- and immune-related genes (EPO, PLAUR, TEK, TGFA, TGFB1) were ultimately selected. Survival analysis showed that the high-risk score on the hypoxia- and immune-related gene signature was significantly associated with adverse survival outcomes. Furthermore, clinical ccRCC samples from our medical center were used to validate the differential expression of the five genes in tumor tissue compared to normal tissue through quantitative real-time polymerase chain reaction (qRT-PCR). However, more clinical trials are needed to confirm these results, and future experimental studies must verify the potential mechanism behind the predictive value of the hypoxia- and immune-related gene signature.

The treatment development for T cell acute lymphoblastic leukemia in children, adolescents, and young adults

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10%-15% of pediatric ALL, and its frequency increases during the adolescent and young adult (AYA) periods. The improvements in pediatric T-ALL outcomes have been achieved through the treatment intensification strategies addressing the cranial radiotherapy omission issue. Furthermore, pediatric-inspired regimens have been adopted for AYA patients with T-ALL, improving outcomes. In Japan, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-T11/JALSG T-ALL-211-U trial has been conducted for newly diagnosed patients with T-ALL aged <25 years and has been shown to have excellent outcomes. While early T cell precursor ALL is not an obvious poor prognostic factor in recent treatment strategies for pediatric T-ALL, the minimal residual disease (MRD) has been recognized as the most reliable prognostic indicator. Therefore, MRD is now widely used in T-ALL clinical trials for risk stratification and stem cell transplantation indications. Further progress in the novel therapeutic approaches can potentially improve the outcomes of pediatric and AYA patients with T-ALL.

Lymph Node Ratio Is a Reliable Prognostic Marker after Neoadjuvant Therapy and Pancreaticoduodenectomy for Pancreatic Cancer, but Does Not Predict the Utility of Adjuvant Therapy

Introduction: The role of additional adjuvant chemotherapy(AT) after neoadjuvant chemotherapy(NAT) and surgical resection for pancreatic ductal adenocarcinoma(PDAC) remains unclear. Lymph node ratio(LNR), defined as number of positive nodes divided by total resected nodes, is a well-established prognostic indicator for PDAC. The objective of this analysis was to determine if LNR predicts survival benefit attained from receipt of AT following NAT and resection. Methods: Patients who underwent pancreaticoduodenectomy after NAT from 2006-2017 with pathologically node-positive PDAC were identified using the National Cancer Database. Patients with metastatic disease or unknown lymph node status were excluded. Patients were grouped as receiving NAT plus AT, or NAT only. LNR within node-positive groups were compared with a cutoff of 0.15. Five-year overall survival was determined by Kaplan-Meier analysis and multivariate(MV) Cox proportional hazards modeling. Results: A total of 1,182 patients were included: 623 with LNR=0.1-0.14 and 559 with LNR>=0.15. Median survival was higher among LNR=0.1-0.14 than with LNR>=0.15(28.8 vs 20.5mos, log-rank p<.001). 606 patients received NAT plus AT, and 576 received NAT only. For patients with LNR=0.1-0.14, receipt of additional AT was associated with improved median survival of 33.9mos compared to 27.3mos(log-rank p=0.050). For LNR>=0.15, receipt of additional AT was associated with improved median survival of 23.3mos vs 18.2mos(log-rank p=0.0024). MV analysis revealed similar survival benefit from AT, with hazard ratios of 0.807(95%CI 0.678-0.960, p=0.0156) for LNR=0.1-0.14 and 0.79(95%CI 0.669-0.942, p=0.0084) for LNR>=0.15. Conclusion: Although LNR is a reliable prognostic indicator for PDAC, it does not predict the utility of AT after receipt of NAT.

ATG7 immunohistochemical expression in malignant pleural mesothelioma. A preliminary report.

Literature evidence has demonstrated a high incidence of asbestos-related malignant pleural mesothelioma (MPM) in a Sicilian town (Biancavilla, Italy), where fluoro-edenite (FE) fibers were discovered some decades ago. As ATG7 immunohistochemical analysis has been ascribed as a prognostic tool of improved survival, we decided to investigate, in MPM patients, exposed and not exposed to FE fibers, the immunohistochemical expression of this autophagy-related protein named ATG7. We analyzed the correlation between ATG7 immunohistochemical level and clinicopathological parameters. Twenty MPM tissue samples, from patients with available clinical and follow-up data, were included in paraffin and processed for immunohistochemistry. The immunohistochemical results confirmed activation of the autophagic process in MPM. Densitometric and morphometric expressions of ATG7 were significantly increased in MPMs when compared to the control tissues. A significant association of a high level of ATG7 with increased survival was demonstrated, with a mean overall survival (OS) of 12.5 months for patients with high expression vs. a mean OS of 4.5 months for patients with low ATG7 expression. In addition, a significant correlation between ATG7 expression and the survival time of MPM patients was observed. This study represents a starting point to hypothesize the prognostic role of ATG7 which could be a reliable prognostic indicator in MPM.

A novel magnetic resonance imaging-based scoring system to predict outcome in neonates born preterm with intraventricular haemorrhage.

AimTo create a magnetic resonance imaging (MRI)‐based scoring system specific to neonates born preterm with intraventricular haemorrhage (IVH), which could serve as a reliable prognostic indicator for later development and might allow for improved outcome prediction, individually‐tailored parental counselling, and clinical decision‐making.MethodThis retrospective, two‐center observational cohort study included 103 infants born preterm with IVH (61 males, 42 females; median gestational age 26wks 6d), born between 2000 and 2016. Term‐equivalent MRI was evaluated using a novel scoring system consisting of 11 items. A total MRI score was calculated and correlated with neurodevelopment between 2 years and 3 years of age. Prediction models for outcome were defined.ResultsThe proposed MRI scoring system showed high correlation and strong predictive ability with regard to later cognitive and motor outcome. The prediction models were translated into easy‐to‐use tables, allowing developmental risk assessment.InterpretationThe proposed MRI‐based scoring system was created especially for infants born preterm with IVH and enables a comprehensive assessment of important brain areas as well as potential additional abnormalities commonly associated with IVH. Thus, it better represents the severity of brain damage when compared with the conventional IVH classification. Our scoring system should provide clinicians with valuable information, to optimize parental counselling and clinical decision‐making.

Association of BMI and Change in Weight With Mortality in Patients With Fibrotic Interstitial Lung Disease

Mortality risk assessment in interstitial lung disease (ILD) is challenging. Our objective was to determine the prognostic significance of BMI and change in weight in the most common fibrotic ILD subtypes. Could BMI and weight loss over time be reliable prognostic indicators in patients with fibrotic ILD? This observational retrospective multicenter cohort study enrolled patients with fibrotic ILD from the six-center CAnadian REgistry for Pulmonary Fibrosis (CARE-PF, derivation) and the ILD registry at the University of California, San Francisco (UCSF, validation). Patients were subcategorized as underweight (BMI< 18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), or obese (BMI > 30). Annual change in weight was calculated for all years of follow-up as the slope of best fit using the least square method based on every available measurement. Separate multivariable analyses evaluated the associations of BMI and change in weight with mortality, adjusting for common prognostic variables. The derivation and validation cohorts included 1,786 and 1,779 patients, respectively. Compared with patients with normal BMI, mortality was highest in patients who were underweight (hazard ratio [HR], 3.19; 95%CI, 1.88-5.43; P< .001) and was lowest in those who were overweight (HR, 0.52; 95%CI, 0.36-0.75; P< .001) or obese (HR, 0.55; 95%CI, 0.37-0.83; P< .001) in the analysis adjusted for the ILD-GAP (gender, age, physiology) Index. Patients who had a weight loss of at least 2kg within 1 year had increased risk of death in the subsequent year (HR, 1.41; 95%CI, 1.01-1.97; P= .04) after adjustment for the ILD-GAP Index and baseline BMI category, with a plateau in risk for patients with greater weight loss. Consistent results were observed in the validation cohort. Both BMI and weight loss are independently associated with 1-year mortality in fibrotic ILD. BMI and weight loss may be clinically useful prognostic indicators in fibrotic ILD.