Prognostic Biomarker In Patients Research Articles

Lipoprotein(a): A New Intensive Care Unit Admission Predictor in Coronavirus Disease 2019 Patients.

Endothelium-related events in patients with coronavirus disease 2019 are linked to a poor prognosis. Lipoprotein(a) plays a role in vascular endothelial cell dysfunction. This research aims to investigate whether baseline serum lipoprotein(a) levels could be a predictor for intensive care unit admission and related clinical parameters in coronavirus disease 2019 patients. The research covers 126 patients who were hospitalized in intensive care unit or the non-intensive care unit in our hospital. This prospective cohort study was conducted from January 2021 to June 2021. The patients who were positive for severe acute respiratory syndrome coronavirus 2 according to real-time polymerase chain reaction test results were included in the study. Two groups were created according to the status of intensive care unit admission. Lipoprotein(a) was studied from blood samples taken at the time of hospital admission. According to the results of the first clinical evaluation, 46 patients were admitted to the intensive care unit and 80 patients were admitted to non-intensive care unit in the hospital. Patients with intensive care unit admission had significantly higher serum lipoprotein(a) levels than patients without intensive care unit admission (40.9 ng/mL and 17.4 ng/mL, P < .001, respectively). The regres- sion analysis revealed that serum lipoprotein(a) levels were independently related to intensive care unit admission (odds ratio 1.242, 95% CI 1.109-1.391, P < .001). In receiver operating characteristic curve analysis, lipoprotein(a) level ≥31.42 ng/mL had 82.6% sensitivity and 72.5% specificity in predicting intensive care unit admission. The risk of intensive care unit admission was seen to be 12.522-fold higher in cases with lipoprotein(a) level ≥31.42. Lipoprotein(a) could be used as a useful biomarker for the triage of coronavirus disease 2019 patients. Baseline serum lipoprotein(a) levels may serve as a useful prognostic biomarker in patients hospitalized for coronavirus disease 2019.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer

BackgroundInterindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent.MethodsWe conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico’s National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS).ResultsWe included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9–147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6–71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6–81.6). Group B: 75.7 months (95% CI 66.8–84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8–76.3) months] than in group A [82.8 (95% CI 78.6–86.9 months] and group B [87.1 (95% CI 79.6–94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031).ConclusionsWhen assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Phenotypic and proteomic analysis of plasma extracellular vesicles highlights them as potential biomarkers of primary Sjögren syndrome.

Sjögren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS.

Prognostic Implication of YY1 and CP2c Expression in Patients with Primary Breast Cancer.

Yin Yang 1 (YY1) is a transcription factor that regulates epigenetic pathways and protein modifications. CP2c is a transcription factor that functions as an oncogene to regulate cell proliferation. YY1 is known to interact with CP2c to suppress CP2c's transcriptional activity. This study aimed to investigate YY1 and CP2c expression in breast cancer and prognostic implications. In this study, YY1 and CP2c expression was evaluated using immunohistochemical staining, Western blot and RT-PCR assays. Of 491 patients with primary breast cancer, 138 patients showed YY1 overexpression. Luminal subtype and early stage were associated with overexpression (p < 0.001). After a median follow-up of 68 months, YY1 overexpression was found to be associated with a better prognosis (disease-free survival rates of 92.0% vs. 79.2%, p = 0.014). In Cox proportional hazards model, YY1 overexpression functioned as an independent prognostic factor after adjustment of hormone receptor/HER2 status and tumor size (hazard ratio of 0.50, 95% CI 0.26-0.98, p = 0.042). Quantitative analysis of YY1 and CP2c protein expression in tumors revealed a negative correlation between them. In conclusion, YY1 overexpression is a favorable prognostic biomarker in patients with breast cancer, and it has a negative correlation with CP2c at the protein level.

Tumor Volume on PSMA PET as a Prognostic Biomarker in Prostate Cancer Patients Treated With Cabazitaxel.

The aim of this study was to evaluate the prognostic value of 68 Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in metastatic castration-resistant prostate cancer patients receiving second-line chemotherapy with cabazitaxel. All patients with metastatic castration-resistant prostate cancer who underwent a PSMA PET/CT within 8 weeks before initiating the cabazitaxel treatment were retrospectively evaluated. The whole-body PSMA total tumor volume (PSMA-TV) was measured for each patient. Other factors such as prostate-specific antigen, hemoglobin, lactate dehydrogenase, and alkaline phosphatase were recorded. A log-rank cutoff finder was used to define the PSMA-TV optimal cutoff. Survival analyses were performed using Cox regression and Kaplan-Meier methods. In total, 32 patients were included, receiving a median of 6 cycles of cabazitaxel (range, 2-10). After a median follow-up of 12 months, 28 patients presented disease progression, and 18 died. Baseline PSMA-TV presented a significant association with progression-free survival (PFS) and overall survival (OS; P = 0.035 and P = 0.002, respectively). Optimal PSMA-TV cutoffs were 515 mL for PFS and 473 mL for OS. Patients with low volume presented longer PFS and OS than those with high volume: median PFS, 21 versus 12 weeks, respectively (hazard ratio, 0.33; P = 0.017); and median OS, 24 versus 8.5 months, respectively (hazard ratio, 0.21; P = 0.002). On the multivariable analyses, PSMA-TV remained an independent predictor of OS ( P = 0.016). Our results show that total tumor volume measured on PSMA PET/CT is a prognostic biomarker in patients treated with cabazitaxel. High PSMA-TV before treatment initiation is associated with shorter PFS and OS.

FBXO5 acts as a novel prognostic biomarker for patients with cervical cancer.

Background: Cervical cancer (CC) remains one of the most common and deadly malignancies in women worldwide. FBXO5, a protein-coding gene, is highly expressed in a variety of primary tumors and promotes tumor progression, however, its role and prognostic value in CC remain largely unknown. Methods: A key differential gene, FBXO5, was screened according to WGCNA based on immunohistochemical assays of clinical samples, multiple analyses of the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, including survival analysis, tumor mutational burden, GO, KEGG, tumor immune infiltration, and chemotherapeutic drug sensitivity, to explore the expression and prognostic value of FBXO5 in CC. The migration and invasiveness of cervical cancer cells following FBXO5 knockdown and overexpression were examined using wound healing and transwell assays, and the viability of cancer cells was assessed using CCK8 and EdU assays. Results: FBXO5 was discovered to be substantially expressed in CC tissues using data from our CC cohort and the TCGA database, and a survival analysis indicated FBXO5 as a predictive factor for poor overall survival in CC patients. In vitro, CC cells were more inclined to proliferate, migrate, and invade when FBXO5 was upregulated as opposed to when it was knocked down.

Osteopontin is a prognostic circulating biomarker in patients with neuroendocrine neoplasms

PurposeOsteopontin (OPN), also called secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and which has been shown to be involved in tumorigenesis and metastasis in many malignancies. Its role in neuroendocrine neoplasms (NEN) remains to be established. The aim of the study was to analyze plasma concentrations of OPN in patients with NEN and to explore its diagnostic and prognostic value as a clinical biomarker.MethodsOPN plasma concentrations were measured in a total of 38 patients with histologically proven NEN at three different time points during the course of disease and therapy (at the start of the study, after 3 and 12 months, respectively) as well as in healthy controls. Clinical and imaging data as well as concentrations of Chromogranin A (CgA) and Neuron Specific Enolase (NSE) were assessed.ResultsOPN levels were significantly higher in patients with NEN compared to healthy controls. High-grade tumors (grade 3) showed the highest OPN levels. OPN levels were neither different between male and female patients nor between different primary tumor sites. OPN correlated significantly with corresponding NSE levels, while there was no correlation with Chromogranin A. High OPN levels above a cutoff value of 200 ng/ml at initial analysis predicted a worsened prognosis with significantly shorter progression-free survival of patients with NEN, which also held true within the subgroup of well-differentiated G1/G2 tumors.ConclusionOur data indicate that high baseline OPN levels in patients with NEN are predictive of an adverse outcome with shorter progression-free survival, even within the group of well differentiated G1/G2 tumors. Therefore, OPN may be used as a surrogate prognostic biomarker in patients with NEN.

High preoperative CEA and systemic inflammation response index (C-SIRI) predict unfavorable survival of resectable colorectal cancer

BackgroundCEA and systemic inflammation were reported to correlate with proliferation, invasion, and metastasis of colorectal cancer. This study investigated the prognostic significance of the preoperative CEA and systemic inflammation response index (C-SIRI) in patients with resectable colorectal cancer.MethodsTwo hundred seventeen CRC patients were recruited from Chongqing Medical University, the first affiliated hospital, between January 2015 and December 2017. Baseline characteristics, preoperative CEA level, and peripheral monocyte, neutrophil, and lymphocyte counts were retrospectively reviewed. The optimal cutoff value for SIRI was defined as 1.1, and for CEA, the best cutoff values were 4.1 ng/l and 13.0 ng/l. Patients with low levels of CEA (< 4.1 ng/l) and SIRI (< 1.1) were assigned a value of 0, those with high levels of CEA (≥ 13.0 ng/l) and SIRI (≥ 1.1) were assigned a value of 3, and those with CEA (4.1–13.0 ng/l) and SIRI (≥ 1.1), CEA (≥ 13.0 ng/l), and SIRI (< 1.1) were assigned a value of 2. Those with CEA (< 4.1 ng/l) and SIRI (≥ 1.1) and CEA (4.1–13.0 ng/l) and SIRI (< 1.1) were assigned a value of 1. The prognostic value was assessed based on univariate and multivariate survival analysis.ResultsPreoperative C-SIRI was statistically correlated with gender, site, stage, CEA, OPNI, NLR, PLR, and MLR. However, no difference was observed between C-SIRI and age, BMI, family history of cancer, adjuvant therapy, and AGR groups. Among these indicators, the correlation between PLR and NLR is the strongest. In addition, high preoperative C-SIRI was significantly correlated with poorer overall survival (OS) (HR: 2.782, 95% CI: 1.630–4.746, P < 0.001) based on univariate survival analysis. Moreover, it remained an independent predictor for OS (HR: 2.563, 95% CI: 1.419–4.628, p = 0.002) in multivariate Cox regression analysis.ConclusionOur study showed that preoperative C-SIRI could serve as a significant prognostic biomarker in patients with resectable colorectal cancer.

Angiogenesis and Hepatocellular Carcinoma: From Molecular Mechanisms to Systemic Therapies.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The hypervascular nature of the majority of HCCs and the peculiar vascular derangement occurring during liver carcinogenesis underscore the importance of angiogenesis in the development and progression of these tumors. Indeed, several angiogenic molecular pathways have been identified as deregulated in HCC. The hypervascular nature and the peculiar vascularization of HCC, as well as deregulated angiogenic pathways, represent major therapeutic targets. To a large extent, intra-arterial locoregional treatments (transarterial-(chemo)embolization) rely on tumor ischemia caused by embolization of tumor feeding arteries, even though this may represent the "primum movens" of tumor recurrence through the activation of neoangiogenesis. Considering systemic therapies, the currently available tyrosine kinase inhibitors (sorafenib, regorafenib, cabozantinib and lenvatinib) and monoclonal antibodies (ramucirumab and bevacizumab, in combination with the anti-PD-L1, atezolizumab) primarily target, among others, angiogenic pathways. Considering the importance of angiogenesis in the pathogenesis and treatment of liver cancer, in this paper, we aim to review the role of angiogenesis in HCC, addressing the molecular mechanisms, available antiangiogenic therapies and prognostic biomarkers in patients receiving these treatments.

Association of a high E2F targets score with survival in hepatocellular carcinoma patients.

4106 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. Multiple staging systems have all been proposed to date; however, the optimal tool for stratification of prognosis is still not universally accepted. E2F targets are the essential component of cell proliferation, thus we hypothesized that a score to quantify E2F activity is expected to reflect the aggressiveness and prognosis of HCC. Methods: Total of 655 HCC patients from TCGA (The Cancer Genome Atlas) -HCC ( n=358), GSE6764 ( n=75), GSE76427 ( n = 115), and GSE89377 ( n=107) cohorts were analyzed. The score was generated using MSigDb Hallmark E2F Targets gene set using Gene Set Variation Analysis. Results: The E2F targets scores of TGCA-HCC patients showed a bimodal distribution, thus high vs. low score groups were divided by median. As expected, high E2F targets enriched all of the Hallmark cell proliferation-related gene sets; E2F targets, G2M checkpoint, MYC targets v1 and v2, and Mitotic spindle. It also enriched gene sets known to aggravate cancer, such as Glycolysis, mTORC1 signaling, DNA repair, and Unfolded protein response. E2F targets were significantly associated with histological grade, tumor size, and stage, as well as proliferation score and MKI67 expression. Furthermore, a higher E2F targets score was significantly associated with higher intra-tumoral genomic heterogeneity and homologous recombination deficiency, suggesting greater tumor aggressiveness. In agreement, E2F targets score correlated with the pathological progression from normal liver, cirrhosis, dysplasia, to early and advanced HCC consistently in two cohorts (GSE6764 and GSE89377). Further, the abundance of hepatocytes, fibroblasts, adipocytes, and lymphatic endothelial cells were all significantly less in high E2F HCC, which reflects proliferative cancer. On the other hand, there was no relationship between E2F and mutation rates or neoantigens. High E2F was associated with high infiltration of anti-cancerous immune cells; CD8, CD4 memory, and Th1 cells, however, there was no difference in cytolytic activity, and it did not enrich any of immune response-related gene sets. High E2F HCC was associated with worse disease-free (DFS), disease-specific (DSS), and overall survival (OS), and this was the case in both early (I and II) and late (III and IV) stages. A multivariate analysis revealed that the E2F targets score was an independent prognostic factor for OS (HR=1.68, 95%CI= 1.15–2.46, p = 0.007) as well as DSS (HR=1.81, 95%CI=1.27–2.59, p = 0.001) in patients with HCC. Conclusions: We found that the E2F targets score not only indicates cell proliferation, but also is associated with cancer aggressiveness and worse survival. Our findings suggest a possible future use of the E2F targets score as a prognostic biomarker in patients with HCC.

Sarcopenia vs body mass index (BMI) as a prognostic biomarker in patients with metastatic clear cell renal cell carcinoma (mCCRCC) in the era of first line immune checkpoint inhibitors (ICIs).

e16515 Background: ICIs are an important systemic treatment option for patients with mCCRCC. Sarcopenia, defined as low muscle mass, is associated with inferior outcomes in mCCRCC. However, there is limited data regarding sarcopenia and overall survival (OS) in patients receiving treatment with ICI-based regimens. Our objective was to evaluate associations between sarcopenia and BMI with OS in patients with mCCRCC receiving first line ICIs. Methods: A retrospective review of patients with mCCRCC receiving first line ICI-based therapy at Fred Hutchinson Cancer Center between 1/2015 to 4/2022 was performed. Patients without CT scans within 75 days of treatment initiation were excluded. Skeletal muscle index (SMI) at the level of L3 was measured using validated techniques. Sarcopenia was classified according to an international definition (SMI &lt; 55 cm2/m2 for men and SMI &lt; 39 cm2/m2 for women). BMI was defined as underweight ( &lt; 19 kg/m2), normal (19-24.99kg/m2), overweight (25-29.99 kg/m2), and obese ( &gt; 30 kg/m2). OS was estimated using the Kaplan-Meier method. Associations with OS were evaluated with Cox proportional hazard model analysis. Results: A total of 96 patients (25% female) with a median age of 62 (Interquartile range, IQR 55-68), met inclusion criteria. Due to missing CT images, 9 (9%) patients were excluded. 10 (11%), 43 (49%), and 22 (25%) were International Metastatic RCC Database Consortium (IMDC) favorable, intermediate, and poor risk respectively (12 unknown). Median follow up was 23 months (IQR 12-35). First-line therapy included ICI monotherapy (N = 15), ipilimumab/nivolumab (N = 49) or ICI/VEGF targeted therapy (N = 23). In total, 43 (49%) patients were sarcopenic. Median OS overall was 42.6 months (IQR 15.9-NR). Two-year OS was 57% in sarcopenic vs 76% in non-sarcopenic patients (Log-Rank p = 0.06). On multivariable analysis adjusted for IMDC risk criteria, age, and gender, SMI (continuous) was independently associated with survival (HR 0.94, 95%CI 0.90-0.99, p = 0.03) while BMI was not significantly associated with OS on univariate or multivariable analyses (p &gt; 0.05). Among the 49 patients receiving ipilimumab/nivolumab combination therapy, sarcopenia was significantly associated with decreased 2-year OS (47% vs. 77%, p = 0.02). Across IMDC risk strata, sarcopenia was significantly associated with decreased 2-year OS in the intermediate risk group only (44% vs. 83%, p = 0.01). Conclusions: Sarcopenia, but not BMI, is independently associated with OS among patients with mCCRCC receiving first line ICI-based regimens. This finding is consistent with the literature suggesting that muscle mass measurement provides an important prognostic biomarker for patients with mCCRCC. SMI could inform treatment selection and adoption of muscle measures when risk-stratifying this population should be considered.

HPV integration as a prognostic biomarker for metastatic anal cancer: A next-generation sequencing ctDNA-based approach.

3525 Background: Anal cancer is an HPV-associated malignancy with increasing prevalence in the United States. Immune checkpoint blockade demonstrates limited efficacy in patients with metastatic squamous cell cancer of the anal canal (mSCCA), and no prognostic or predictive biomarkers have demonstrated clinical utility in this population. Available circulating tumor DNA (ctDNA) assays have utilized ddPCR methodologies to report only the most common HPV types (HPV-16 and HPV-18) and HPV copy numbers. To extend the utility of an HPV ctDNA assay, we created a novel next-generation sequencing HPV ctDNA assay to analyze HPV integration as a prognostic biomarker for patients with mSCCA. Methods: Using an IRB-approved protocol, ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. HPV type, HPV copy number, and HPV integration status/locus were determined using a bioinformatic pipeline developed in-house. A Fisher's exact test was used to compare radiographic and ctDNA changes in response to systemic treatment. Unpaired t-tests were used to compare demographics between patients with HPV integration (I) or no integration (NI) status in the ctDNA. Median survival was estimated (Kaplan Meier) and compared according to integration status using a log-rank test. Results: 68 plasma samples from 27 patients with mSCCA were analyzed. While HPV-16 was detected in ctDNA of all 27 patients, five patients had additional oncogenic HPV types [HPV-18 (2), HPV-45 (2), HPV-73 (1)]. Radiographic changes in metastatic disease volume were concordant with HPV copy number changes in the ctDNA (odds ratio 12.2, 95% confidence interval (CI) 2.0-75; p = .007). HPV integration events were detected in the ctDNA for 16 (59%) patients (median 2, range 1-7 unique events per patient). For the 23 patients with mSCCA who received anti-PD1 immunotherapy (15 I, 8 NI), there were no differences in age (60 vs 59 years, p = .88) or prior lines of treatment (3.0 vs 3.5, p = .72). There was a trend towards improved median progression-free survival for NI ctDNA status (5.8 vs 3.2 months, hazard ratio (HR) 1.8, 95% CI .71-4.5). Relative to NI status, I status was associated with worse overall survival rates (OS) (22.5 vs 44.9 months, HR 5.0, 95% CI 1.5-17, p = .005). Conclusions: Detection of HPV integration status for all HPV types is feasible using a ctDNA-based approach for patients with SCCA. HPV integration was prognostic for worse OS in patients with mSCCA. Identification of HPV integration as a novel prognostic biomarker for survival outcomes in mSCCA warrants further evaluation in larger clinical trials.

P-213 Prognostic biomarkers in patients with oesophago-gastric cancer treated with immunotherapy

P-213 Prognostic biomarkers in patients with oesophago-gastric cancer treated with immunotherapy

FRI-404 - A systems medicine approach for the identification of potential prognostic biomarkers in patients with acute decompensation of cirrhosis

FRI-404 - A systems medicine approach for the identification of potential prognostic biomarkers in patients with acute decompensation of cirrhosis

C-reactive protein (CRP) as a prognostic biomarker in patients with bladder cancer: A meta-analysis.

e16502 Background: CRP is an acute phase reactant synthesized by hepatocytes in response to inflammatory cytokines including interleukin-6. Peripheral blood CRP, a routinely measured analyte, may reflect tumor microenvironments skewed towards tumor-promoting inflammation. CRP may therefore represent an attractive biomarker to select patients with bladder cancer (BCa) more likely to benefit from therapies directed at modulating tumor-promoting inflammation. Methods: A systematic review was performed to identify studies reporting outcomes based on pre-treatment CRP values in patients with localized and advanced BCa and urothelial carcinoma (UC). The hazard ratio (HR) of overall survival (OS), cancer-specific survival (CSS), relapse-free survival (RFS), and progression-free survival (PFS) between groups with high and low CRP values as defined in each study was extracted. Meta-analysis using the random-effect model was performed to pool HR. Meta-regression analysis was conducted to assess the relationship between CRP cutoff and HR for OS. Subgroup analyses were performed according to clinical disease state and therapies administered. Heterogeneity was assessed using I2 statistics. Results: Overall, 938 articles were identified at initial screening; 22 studies comprising 2,899 patients were included in the meta-analysis. For OS, 17 datasets from 16 studies were used. High CRP levels were associated with decreased OS (HR=2.03, 95%CI:1.67-2.47, p&lt;0.01) although high heterogeneity was observed (I2=91%). Subgroup analyses according to anticancer interventions showed that high CRP values were related to shorter OS, particularly in patients treated with immune checkpoint blockade (ICB; HR=1.78, 95%CI: 1.47-2.15, p&lt;0.01). In meta-regression analysis, the correlation between CRP cutoff value and OS HR was not observed when all 16 studies were considered (Regression coefficient=0.03, 95%CI: -0.13-0.18, p=0.73). However, CRP cutoff value was significantly associated with the HR for OS (Regression coefficient=-0.21, 95%CI: -0.36 to -0.06, p=0.01) when the analysis was limited to eight studies assessing ICB in advanced BCa/UC. Pooled HR of CSS, RFS, and PFS is shown in Table. Conclusions: High CRP values were associated with poorer clinical outcomes in patients with BCa/UC, particularly among patients with advanced disease treated with ICB. CRP may represent an attractive biomarker to enrich populations more likely to benefit from therapies that modulate tumor-promoting inflammation. [Table: see text]

MCM10: An effective treatment target and a prognostic biomarker in patients with uterine corpus endometrial carcinoma.

Molecular profiling has been applied for uterine corpus endometrial carcinoma (UCEC) management for many years. The aim of this study was to explore the role of MCM10 in UCEC and construct its overall survival (OS) prediction models. Data from TCGA, GEO, cbioPotal and COSMIC databases and the methods, such as GO, KEGG, GSEA, ssGSEA and PPI, were employed to bioinformatically detect the effects of MCM10 on UCEC. RT-PCR, Western blot and immunohistochemistry were used to validate the effects of MCM10 on UCEC. Based on Cox regression analysis using the data from TCGA and our clinical data, two OS prediction models for UCEC were established. Finally, the effects of MCM10 on UCEC were detected in vitro. Our study revealed that MCM10 was variated and overexpressed in UCEC tissue and involved in DNA replication, cell cycle, DNA repair and immune microenvironment in UCEC. Moreover, silencing MCM10 significantly inhibited the proliferation of UCEC cells in vitro. Importantly, based on MCM10 expression and clinical features, the OS prediction models were constructed with good accuracy. MCM10 could be an effective treatment target and a prognostic biomarker for UCEC patients. The OS prediction models might help establish the strategies of follow-up and treatment for UCEC patients.

Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities. CSF and serum samples of 15 SCI and ten healthy participants were included in the study. The neurological assessments were scored on admission and at discharge from the hospital using the American Spinal Injury Association Impairment Score (AIS) grades. The CSF and serum concentrations of SBDP150, S100B, GFAP, NF-L, UCHL-1, Tau, and IL-6 were significantly higher in SCI patients when compared with the control group. The CSF GBDP 38/44K, UCHL-L1, S100B, GFAP, and Tau levels were significantly higher in the AIS A patients. This study demonstrated a strong correlation between biomarker levels in the diagnosis and injury severity of SCI but no association with short-term outcomes. Future prospective controlled studies need to be done to support the results of this study.

E2F target score is associated with cell proliferation and survival of patients with hepatocellular carcinoma

BackgroundE2F target genes are essential for the cell cycle. A score that quantifies its activity is expected to reflect the aggressiveness and prognosis of hepatocellular carcinoma. MethodsCohorts of hepatocellular carcinoma patients (total n = 655) from The Cancer Genome Atlas, GSE89377, GSE76427, and GSE6764 were analyzed. The cohorts were divided into high versus low by the median. ResultsAll the Hallmark cell proliferation-related gene sets were consistently enriched in hepatocellular carcinoma with high E2F targets score, and E2F score was associated with grade, tumor size, American Joint Committee on Cancer staging, proliferation score, and MKI67 expression, as well as with less abundance of hepatocytes and stromal cells. E2F targets enriched DNA repair, mTORC1 signaling, glycolysis, and unfolded protein response gene sets and were significantly associated with the higher intratumoral genomic heterogeneity, homologous recombination deficiency, and progression of hepatocellular carcinoma. On the other hand, there was no relationship between E2F targets and mutation rates or neoantigens. High E2F hepatocellular carcinoma did not enrich any of the immune-response–related gene sets but was associated with high infiltration of Th1, Th2 cells, and M2 macrophage; however, there was no difference in cytolytic activity. In both early (I and II) and late (III and IV) stages of hepatocellular carcinoma, a high E2F score was associated with worse survival and was an independent prognostic factor for overall and disease-specific survival in patients with hepatocellular carcinoma. ConclusionThe E2F target score, associated with cancer aggressiveness and worse survival, could be used as a prognostic biomarker in patients with hepatocellular carcinoma.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of Src Family Kinases in Hepatocellular Carcinoma.

Src family kinases (SFKs) belong to the non-receptor protein tyrosine kinase family and are generally dysregulated in a variety of tumors. This study aimed to thoroughly investigate the mutation status, expression level, prognostic value and relationship with immune infiltration of SFKs in hepatocellular carcinoma (HCC). TIMER2.0, UALCAN, cBioPortal, Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter were used to analyze the differential expression, genetic alteration, prognostic value and immune cell infiltration of SFKs in HCC patients. Furthermore, we used quantitative real-time PCR (qPCR) and western blot (WB) analysis to measure SFKs mRNA and protein expression in matching specimens of normal tissue and HCC. We analyzed the biological effects of FYN in Huh7 cells and subcutaneous xenograft tumor model. We also studied the biological effects of SRC on Huh7 cells. The mRNA expression levels of LYN, SRC and SRM were elevated in HCC tissues, whereas FYN was reduced. Approximately 10% genetic alterations rate of SFKs was observed in HCC. The mRNA levels of BLK, BRK, FRK, FYN, LCK, LYN, SRC, SRM and YES were correlated with clinical cancer stage. Elevated FYN mRNA levels in HCC were positively correlated with overall survival (OS), whereas SRC was negatively correlated with OS. All SFKs members in HCC were significantly associated with at least half of the six immune-infiltrating cells, including B cells, macrophages, dendritic cells, neutrophils, CD4+ T cells and CD8+ T cells. Furthermore, we confirmed that the protein expression level of FYN was decreased in patients with HCC and in a human hepatoma cell line. Overexpression of FYN suppressed Huh7 cell proliferation, migration, invasion, and tumorigenesis in xenograft nude mice. Knockdown of SRC inhibited Huh7 cell proliferation, migration and invasion. Dysregulated FYN and SRC expression in HCC is associated with poor prognosis and may be used as novel prognostic biomarkers in patients with HCC.

ZDHHC15 promotes glioma malignancy and acts as a novel prognostic biomarker for patients with glioma

BackgroundGlioma is the most common and aggressive tumor in the adult brain. Recent studies have indicated that Zinc finger DHHC-type palmitoyltransferases (ZDHHCs) play vital roles in regulating the progression of glioma. ZDHHC15, a member of the ZDHHCs family, participates in various physiological activities in the brain. However, the biological functions and related mechanisms of ZDHHC15 in glioma remain poorly understood.MethodsData from multiple glioma-associated datasets were used to investigate the expression profiles and potential biological functions of ZDHHC15 in glioma. Expression of ZDHHC15 and its association with clinicopathological characteristics in glioma were validated by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemical experiments. GO enrichment analysis, KEGG analysis, GSEA analysis, CCK-8, EdU, transwell, and western blotting assays were performed to confirm the functions and mechanism of ZDHHC15 in glioma. Moreover, we performed Kaplan-Meier analysis and Cox progression analysis to explore the prognostic significance of ZDHHC15 in glioma patients.ResultsZDHHC15 expression was significantly up-regulated in glioma and positively associated with malignant phenotypes. Results from the GO and KEGG enrichment analysis revealed that ZDHHC15 was involved in regulating cell cycle and migration. Knockdown of ZDHHC15 inhibited glioma cell proliferation and migration, while overexpression of ZDHHC15 presented opposite effects on glioma cells. Besides, results from GSEA analysis suggested that ZDHHC15 was enriched in STAT3 signaling pathway. Knockdown or overexpression of ZDHHC15 indeed affected the activation of STAT3 signaling pathway. Additionally, we identified ZDHHC15 as an independent prognostic biomarker in glioma, and higher expression of ZDHHC15 predicted a poorer prognosis in glioma patients.ConclusionOur findings suggest that ZDHHC15 promotes glioma malignancy and can serve as a novel prognostic biomarker for glioma patients. Targeting ZDHHC15 may be a promising therapeutic strategy for glioma.