Prognostic Marker In Cancer Patients Research Articles

Novel Oncogenic Value of C10orf90 in Colon Cancer Identified as a Clinical Diagnostic and Prognostic Marker

C10orf90, a tumor suppressor, can inhibit the occurrence and development of tumors. Therefore, we investigated the gene function of C10orf90 in various tumors using multiple pan-cancer datasets. Pan-cancer analysis results reveal that the expression levels of C10orf90 vary across different tumors and hold significant value in the clinical diagnosis and prognosis of patients with various tumors. In some cancers, the expression level of C10orf90 is correlated with CNV, DNA methylation, immune subtypes, immune cell infiltration, and drug sensitivity in the tumors. In particular, in COAD, the C10orf90 gene is implicated in multiple processes associated with COAD. Cell experiments demonstrate that C10orf90 suppresses the proliferation and migration of colon cancer cells while promoting apoptosis. In summary, C10orf90 plays a role in the onset and progression of various cancers and could potentially serve as an effective diagnostic and prognostic marker for cancer patients. Notably, in COAD, C10orf90 inhibits the proliferation and migration of colon cancer cells, induces apoptosis, and is linked to the advancement of colon cancer.

Long non-coding RNA LINC-PINT is associated with favorable prognosis in cancer patients: a systematic review and meta-analysis.

There is growing evidence that long non-coding RNA long iatrogenic non-protein-coding RNA p53-induced transcript (LINC-PINT) is highly expressed in cancer tissue and is associated with the prognosis of cancer patients. The present study systematically analyzed the prognostic significance of LINC-PINT expression in cancer patients. We aimed to reveal the association between LINC-PINT expression and survival in cancer patients. We collected eligible studies through the PubMed, Embase, and Cochrane library searches until February 1, 2024. We collected the following data from the enrolled studies: first author, publication year, country, cancer type, case number, cancer stage, detection method and cut-off value of LINC-PINT expression, follow-up period, and survival outcome. The prognostic significance of LINC-PINT expression was evaluated by conducting a meta-analysis. StataSE17 (Stata, College Station, TX, USA) was used for all analyses. Eleven eligible studies with 2,876 cancer patients were collected. The pooled results revealed that LINC-PINT expression was associated with favorable overall survival (OS) and disease-free survival (DFS) in cancer patients [for OS, hazard ratio (HR) =0.72, 95% confidence interval (CI): 0.64-0.80, P<0.001; for DFS, HR =0.70, 95% CI: 0.60-0.82, P<0.001]. LINC-PINT expression was associated with favorable OS and DFS, and it may serve as a valuable prognostic marker in cancer patients.

Exploring the prognostic impact of absolute lymphocyte count in patients treated with immune-checkpoint inhibitors

BackgroundThe role of immune checkpoint inhibitors (ICI) expands but affordable and reproducible prognostic biomarkers are needed. We investigated the association between baseline and 3-month absolute lymphocyte count (ALC) and survival for patients on ICI.MethodsA retrospective study investigated patients who received ICI July 2014—August 2019. Survival probabilities were calculated for lymphocyte subsets. Univariate and multivariate analyses were performed to investigate risk factors for lymphopenia.ResultsAmong 179 patients, median age was 62 and 41% were female. The most common diagnoses were melanoma (41%) and lung cancer (40%). Median PFS was 6.5 months. 27% had baseline lymphopenia (ALC < 1 × 109cells/L) and no significant difference in PFS or OS to those with normal ALC. However, 31% had lymphopenia at 3 months and significantly shorter OS than those without (9.8 vs 18.3 months, p < 0.001). Those with baseline lymphopenia who recovered counts at 3 months had no difference in PFS (median NR vs 13.0 months, p = 0.48) or OS (22 vs 18.3 months, p = 0.548) to those never lymphopenic. The strongest risk factor for lymphopenia on multivariable analysis was previous radiation therapy (RT).Conclusions3-month lymphopenia is a negative prognostic marker in cancer patients on ICI. Previous RT is significantly associated with lymphopenia.

Abstract LB338: Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma

Abstract Background: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. Methods: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. Results: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. Conclusion: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients. Citation Format: Jeongsoo Kim, Tae-Jin Kim, Sehyun Chae, Hyojeong Ha, Yejin Park, Seon Ah Lim, Hyemin Lee, Younji Sim, Seyoung Oh, Geon Mo Koo, Minkyung Jo, Daehee Hwang, Kyung-Mi Lee. Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB338.

Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma

BackgroundIn the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244.MethodsTo directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments.ResultsCD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244−/− bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors.ConclusionOur study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

Prognostic significance of the Gustave Roussy immune (GRIm) score in cancer patients: a meta-analysis

Background The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients. Methods Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis. Results Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73–2.48; p < 0.0001; I2 = 62%) and progression-free survival (HR = 1.42; 95%CI: 1.22–1.66; p < 0.0001; I2 = 36%). The prognostic values of GRIm on overall survival and progression-free survival were observed across various tumour types and tumour stages. Sensitivity analysis supported the stability and reliability of the above results. Conclusion Our evidence suggested that the GRIm score could be a valuable prognostic marker in cancer patients, which can be used by clinicians to stratify patients and formulate individualized treatment plans.

Abstract LB270: LINGO2-microRNA cluster controls oral cancer stemness ability and cancer progression

Abstract Cancer recurrence and metastasis are the primary reasons for treatment failure in late-stage oral cancer. Cancer stem cells are the root of cancer recurrence and metastasis. By using the microRNAome analysis of Taiwan OSCC cohort, we found miR-876-3p was highly correlated to OSCC recurrence. The precursor miR-876 promoted in vitro OSCC cell proliferation, migration, and cancer stemness and regulated several cancer stemness-relative genes such as NANOG, OCT4, and LIN28A expression. miR-876 and miR-873 are located in the second intron of the 5’-untransalation region (5’-UTR) at the alternative variant leucine-rich repeat and Ig domain containing 2 (LINGO2). Interestingly, only OSCC cells presented LINGO2 protein expression but did not show in primary oral keratinocytes (HOK). The unique CpG islands at the alternative transcription start site of LINGO2 hinted at crucial epigenetic regulation that controls LINGO2 activation. Silencing of LINGO2 expression reduced OSCC cell growth and cancer stemness abilities. LINGO2 expression was higher in OSCC tumor tissue than in adjacent normal tissue in both Taiwan and The Cancer Genome Atlas (TCGA) head and neck cancer cohorts. Moreover, LINGO2 also served as a poor prognostic marker in cancer patients' overall and recurrent free survival time. In summary, we found a novel LINGO2-microRNA cluster that regulates OSCC stemness and metastasis abilities. Those cancer specific expressions may provide a new therapy niche in OSCC cancer therapy. Citation Format: Wei-Min Chang, Li-Jie Li, Che-Hsuan Lin, Michael Hsiao, Peter Mu-Hsin Chang. LINGO2-microRNA cluster controls oral cancer stemness ability and cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB270.

Prognostic Nutritional Index as a Predictor of Mortality in 101,616 Patients Undergoing Hemodialysis.

High mortality in dialysis patients is linked to malnutrition and inflammation. Prognostic nutritional index (PNI), calculated from serum albumin level and total lymphocyte count, has been developed as a prognostic marker for cancer patients. We investigated the clinical utility of PNI in predicting mortality in patients undergoing hemodialysis. Thus, 101,616 patients who initiated hemodialysis in United States dialysis centers between 2007 and 2011 were included in this retrospective cohort study. Using the Cox regression model, we assessed the relationship between PNI and mortality. Further, the predictive value of PNI for one-year mortality was compared with that of its constituent using area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. Higher PNI quartiles were incrementally associated with lower mortality; in patients with PNI values of 39.5-&lt;43.1, 43.1-&lt;46.6, and ≥46.6 (reference: PNI &lt; 39.5), case-mix adjusted hazard ratios (95% confidence intervals) were 0.66 (0.64, 0.68), 0.49 (0.48, 0.51), and 0.36 (0.34, 0.37), respectively. PNI predicted mortality better than serum albumin level or total lymphocyte count alone. In the subgroup analysis, PNI performed well in predicting mortality in patients aged &lt; 65 years. Our results indicate that PNI is a simple and practical prognostic marker in patients undergoing hemodialysis.

Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

Long non-coding RNA ANRIL promotes chemoresistance in triple-negative breast cancer via enhancing aerobic glycolysis

AimslncRNA ANRIL expression is dysregulated in many human cancers and is thus a useful prognostic marker for cancer patients. However, whether ANRIL is involved in drug resistance in triple-negative breast cancer (TNBC) has not yet been investigated. Main methodsA luciferase reporter assay was conducted to verify the binding between miR-125a and ANRIL. RT-PCR and western blotting were performed to detect the expression of miR-125a, ANRIL, and ENO1. Glycolysis stress was assessed using the Seahorse extracellular flux analyzer. Functional studies were performed using both in vitro and in vivo xenograft models. Key findingsANRIL was markedly upregulated in both patients with TNBC and TNBC cell lines. Knockdown of ANRIL increased the cytotoxic effect of ADR and repressed cellular glycolytic activity in TNBC cells. Mechanistic analysis showed that ANRIL may act as a competing endogenous RNA of miR-125a to relieve the repressive effect of miR-125a on its target glycolytic enzyme enolase (ENO1). Notably, 2-deoxy-glucose attenuated ANRIL-induced increase in drug resistance in TNBC cells. SignificanceThese results indicate that knockdown of ANRIL plays an active role in overcoming drug resistance in TNBC by inhibiting glycolysis through the miR-125a/ENO1 pathway, which may be useful for the development of novel therapeutic targets for treating patients with TNBC, especially those with drug resistance.

The Role of Cytochrome P450 2J2 in Cancer: Cell Protector, Therapeutic Target, or Prognostic Marker?

Cytochrome P450 2J2 (CYP2J2) is one of the recently discovered enzymes that is involved in the metabolism of several drugs. It is mainly an extrahepatic enzyme which can, to some extent, explain some the drugs’ side effects such as cyclophosphamide (Cy). Cyclophosphamide is an alkylating agent that is commonly used in conditioning prior to stem cell transplantation. It is a prodrug that is bio-activated by several CYPs including CYP2J2. Cy is known to have several side effects and its extrahepatic activation by CYP2J2 may explain the mechanism of some of these side effects. On the other hand, CYP2J2 is overexpressed in several types of cancer and its inhibition (e.g. by Cy) reduces the cancer cells survival. Taken together, CYP2J2 is considered as a potential therapeutic target and prognostic marker for cancer patients in addition to its role in drugs extrahepatic metabolism.

A Method to Identify Potential Prognostic Markers Across Distinct Tumor Types.

The identification of novel biomarkers in cancer patients often requires both survival and gene expression analyses. The Kaplan-Meier survival analysis is one of the most common methods to assess the fraction of subjects living for a certain amount of time.Here, we describe a method for researchers to identify potential prognostic markers across distinct tumor types. We utilize The Cancer Genome Atlas (TCGA) as this is one of the most extensive and successful cancer genomics programs to date that includes expression data and clinical follow-up information for up to 33 distinct tumor types. Nevertheless, the method described here can also be applied to any open-source dataset where the RNA expression and clinical outcome are provided.We provide detailed practical instructions and advices for investigators to be able to successfully identify prognostic markers in cancer patients.

Pretreatment Albumin-to-Alkaline Phosphatase Ratio Is a Prognostic Marker in Lung Cancer Patients: A Registry-Based Study of 7077 Lung Cancer Patients.

Simple SummarySince the albumin-to-alkaline phosphatase ratio (AAPR) has shown promising prognostic prediction in cancer patients, the prognostic value of the AAPR was evaluated in a large cohort of 7077 lung cancer patients. We combined patient data from the Danish Lung Cancer Registry and the clinical laboratory information system (LABKA) and showed that a low AAPR was independently associated with an inferior median overall survival in non-small cell lung cancer patients and small cell lung cancer patients. Furthermore, data indicated a level-dependent correlation between the AAPR and survival and that the AAPR added additional prognostic value to the already well-established prognostic markers in lung cancer. Therefore, if our findings are validated in the future, the AAPR should be incorporated as a factor in the general prognostication of lung cancer patients.The albumin-to-alkaline phosphatase ratio (AAPR) is a novel promising prognostic marker in cancer patients. However, the evidence for its significance in lung cancer is scarce. Therefore, we assessed the prognostic value of the AAPR in a large cohort of lung cancer patients. Data on lung cancer patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and combined with data on the pretreatment serum AAPR level extracted from the clinical laboratory information system (LABKA). AAPR tertiles were applied as cutoffs. Cox proportional hazard models assessed the prognostic value of the AAPR. In total, 5978 non-small cell lung cancer (NSCLC) patients and 1099 small cell lung cancer (SCLC) patients were included. Decreasing AAPR level was significantly associated with declining median overall survival (OS) in NSCLC patients (medium vs. low AAPR, adjusted HR = 0.73 (95% confidence interval (CI) 0.68–0.79); high vs. low AAPR, adjusted HR = 0.68 (95% CI 0.62–0.73)) and in SCLC patients (medium vs. low AAPR, adjusted HR = 0.62 (95% CI 0.52–0.74); high vs. low, adjusted HR = 0.59 (95% CI 0.50–0.70)). In conclusion, the AAPR was an independent prognostic factor in NSCLC and SCLC patients. The correlation seems to be level dependent, with reducing survival found to be associated with decreasing AAPR level.

Systemic Inflammation Response Index as a Prognostic Marker in Cancer Patients: A Systematic Review and Meta-Analysis of 38 Cohorts.

BackgroundThe systemic inflammation response index (SIRI), a novel and cost-effective serum biomarker, is associated with prognosis in patients with cancer. However, the prognostic value of the SIRI in cancer remains unclear. This study aimed to evaluate the potential role of the SIRI as a prognostic indicator in cancer.MethodsReports in which the prognostic value of the SIRI in cancer was evaluated were retrieved from electronic databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic significance of the SIRI. The odds ratio (OR) was also calculated to explore the association between the SIRI and clinicopathological features.ResultsThis study included 30 retrospective studies with 38 cohorts and 10 754 cases. The meta-analysis indicated that a high SIRI was associated with short overall survival (OS) (HR = 2.04, 95% CI = 1.82–2.29, P < .001) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 2.08, 95% CI = 1.84–2.34, P < .001). Subgroup analysis showed that the prognostic value of the SIRI was significant in all kinds of cancer included. Moreover, the SIRI was significantly correlated with sex, tumor size, T stage, N stage, TNM stage, and lymphovascular invasion.ConclusionThe pretreatment SIRI could be a promising universal prognostic indicator in cancer.

Activin-A impedes the establishment of CD4+ T cell exhaustion and enhances anti-tumor immunity in the lung

BackgroundAlthough tumor-infiltrating T cells represent a favorable prognostic marker for cancer patients, the majority of these cells are rendered with an exhausted phenotype. Hence, there is an unmet need to identify factors which can reverse this dysfunctional profile and restore their anti-tumorigenic potential. Activin-A is a pleiotropic cytokine, exerting a broad range of pro- or anti-inflammatory functions in different disease contexts, including allergic and autoimmune disorders and cancer. Given that activin-A exhibits a profound effect on CD4+ T cells in the airways and is elevated in lung cancer patients, we hypothesized that activin-A can effectively regulate anti-tumor immunity in lung cancer.MethodsTo evaluate the effects of activin-A in the context of lung cancer, we utilized the OVA-expressing Lewis Lung Carcinoma mouse model as well as the B16F10 melanoma model of pulmonary metastases. The therapeutic potential of activin-A-treated lung tumor-infiltrating CD4+ T cells was evaluated in adoptive transfer experiments, using CD4−/−-tumor bearing mice as recipients. In a reverse approach, we disrupted activin-A signaling on CD4+ T cells using an inducible model of CD4+ T cell-specific knockout of activin-A type I receptor. RNA-Sequencing analysis was performed to assess the transcriptional signature of these cells and the molecular mechanisms which mediate activin-A’s function. In a translational approach, we validated activin-A’s anti-tumorigenic properties using primary human tumor-infiltrating CD4+ T cells from lung cancer patients.ResultsAdministration of activin-A in lung tumor-bearing mice attenuated disease progression, an effect associated with heightened ratio of infiltrating effector to regulatory CD4+ T cells. Therapeutic transfer of lung tumor-infiltrating activin-A-treated CD4+ T cells, delayed tumor progression in CD4−/− recipients and enhanced T cell-mediated immunity. CD4+ T cells genetically unresponsive to activin-A, failed to elicit effective anti-tumor properties and displayed an exhausted molecular signature governed by the transcription factors Tox and Tox2. Of translational importance, treatment of activin-A on tumor-infiltrating CD4+ T cells from lung cancer patients augmented their immunostimulatory capacity towards autologous CD4+ and CD8+ T cells.ConclusionsIn this study, we introduce activin-A as a novel immunomodulatory factor in the lung tumor microenvironment, which bestows exhausted CD4+ T cells with effector properties.

COVID-19 disease and malignant cancers: The impact for the furin gene expression in susceptibility to SARS-CoV-2.

Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin's expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN-201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin's high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.

Peripheral Blood Oxygen Saturation: A Non-invasive Prognostic Marker in Cancer Patients Treated with Radiation Therapy- A Pilot Study

Aims: 1. To evaluate the prognostic value of SpO2 in cancer patients 2. To correlate between daily SpO2 values and tumor response to radiation. Background: Tumor hypoxia is an important prognostic factor in Oncology. It plays an important role in tumorogenesis, radiation resistance and tumor progression. Many invasive and in-vitro methods are available to assess the hypo-oxygenated status of tumors. Objective: We evaluated if SpO2 values measured from pulse oximetry could be used as an adjunct prognostic and predictive factor in oncology patients. Methods: Ten consecutive patients with locally advanced, non-metastatic disease were evaluated. Daily SpO2 measurements throughout the treatment and weekly haemoglobin values were noted. All patients received radical intent radiation therapy. Patients were categorised into two groups: poor SpO2 (&lt;97mmHg) and better SpO2 (≥98mmHg). Results: Tumour response was higher in patients with better SpO2 (≥98mmHg). Patients with poor SpO2 (&lt;97mmHg) presented with bulkier disease at diagnosis. Conclusion: Role of SpO2 as a prognostic and predictive factor should be explored further with in vitro and pH studies.

Long-term outcomes of patients investigated for suspected upper extremities deep venous thrombosis irrespective of imaging results.

Outcome data are limited for upper extremity deep venous thrombosis (UEDVT). The outcomes of patients investigated for, but without UEDVT remain uncertain. Retrospective analysis of clinical records of adult patients undergoing Doppler ultrasound for potential UEDVT between 1 January 2007 and 31 December 2014 was undertaken. Primary outcome was all-cause mortality. Secondary outcomes were new cancer diagnosis and thromboembolic recurrence. The final cohort (n = 528) comprised 25 primary UEDVT, 100 secondary UEDVT, 40superficial-venous thrombosis and 363 without thrombus patients. There were 207 deaths. Survival was higher in primary than in secondary UEDVT (log-rank p < 0.0001) or those without thrombus (log-rank p = 0.001). Pre-existing cancer [hazard ratio 3.6 (95% confidence interval 1.5-8.9)] was the biggest independent predictor of mortality and leading cause of death. Developing UEDVT was a poor prognostic marker in cancer patients. There was high early mortality regardless of radiological findings, with the exception of primary UEDVT. Prospective studies evaluating aggressive treatment of underlying comorbidities in these patients are needed.

Association Between Plasma Brain Natriuretic Peptide and Overall Survival in Patients With Advanced Cancer: Preliminary Findings

ContextAtrial and brain natriuretic peptides (ANP and BNP) are established diagnostic and prognostic markers in heart failure, but their utility in patients with advanced cancer is unclear. ObjectivesOur objective was to examine the association between plasma natriuretic peptides and survival in patients with advanced cancer without clinical evidence of heart failure. MethodsThis exploratory analysis of a multicenter, randomized clinical trial of cancer patients receiving hospice care assessed the association between elevated plasma ANP, BNP, or Pro-BNP (cutoffs of >77, 100, and 900 pg/mL, respectively) and overall survival. Time-to-event analyses, including multivariate Cox regression, were conducted. ResultsAmong 97 patients, the mean age was 67.2 years and the overall survival was 16 days (95% CI, 13–23 days). ANP, BNP, and Pro-BNP were elevated in 29 of 36 (81%), nine of 23 (39%), and 32 of 38 (84%) patients, respectively. Elevated ANP, BNP, or Pro-BNP was associated with worse survival (median 14 vs. 21 days; P = 0.02). BNP or Pro-BNP was inversely associated with overall survival (hazard ratio = 2.27; 95% CI, 1.29–3.97) in univariate Cox regression analysis, and remained significant in multivariate Cox regression analysis (hazard ratio = 3.09; 95% CI, 1.40–6.84) after adjusting for treatment group and known prognostic variables such as performance status, albumin, creatinine, delirium, dyspnea, and anorexia. Elevated ANP alone was not significantly associated with survival (P = 0.17). ConclusionOur preliminary findings suggest that BNP or Pro-BNP may be a novel objective prognostic marker in cancer patients without heart failure. Further research is needed to confirm these findings.

Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24−, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance.