Marker For Metastasis Research Articles

Caffeic Acid Phenethyl Ester Suppresses Cytokine- and Chemotherapy-Induced Inflammation in Triple-Negative Breast Cancer via NF-κB Signalling

Background: Triple-negative breast cancer (TNBC) remains a significant clinical challenge due to its aggressive nature and lack of targeted therapies. In TNBC, inflammation contributes to tumour progression by promoting cell proliferation, survival, and migration. It may be triggered by cytokines such as TNF-α or chemotherapeutic agents such as doxorubicin (DOX). Thus, identifying agents that suppress inflammation in TNBC is of prime interest. Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory compound that exhibits selective cytotoxicity against some cancer cells. However, its impact on cytokine or chemotherapy induced inflammation in TNBC has not yet been explored. Aim: This study aimed to investigate the effects of CAPE on TNF-α- or DOX-induced inflammation and metastatic markers in TNBC. Methods: The effects of CAPE and DOX on TNBC cell viability and migration were assessed using the MTT and wound healing assays, respectively. The effect of CAPE on the expression of pro-inflammatory cytokines, epithelial-mesenchymal transition (EMT) markers, and tumour invasion markers was evaluated using RT-qPCR. Results: CAPE inhibited TNF-α-induced proliferation and migration of TNBC cells. CAPE also suppressed TNF-α- and DOX-induced upregulation of NF-κB-regulated pro-inflammatory genes, IL-1B, IL-6, IL-8, and TNF-α, corroborating the evidence that CAPE suppresses NF-κB signalling. Additionally, CAPE suppressed EMT in TNF-α–stimulated and DOX-treated cells by downregulating vimentin and VCAM1. Furthermore, CAPE reduced the expression of the cancer invasion markers MMP2 and MMP9. Conclusions: We demonstrated the anticancer potential of CAPE and its ability to suppress cytokine and chemotherapy-induced inflammation. This study offers novel insights into the role of CAPE in suppressing inflammation and metastasis markers in TNBC, specifically in the context of TNF-α and DOX-induced NF-κB signalling. These findings underscore the urgent need to further study CAPE as a possible adjuvant for treating patients with TNBC, especially those undergoing chemotherapy.

A study of the role of androgen receptor and androgen receptor variant 7 in TNBC patients and the effect of their targeting by Enzalutamide and EPI-001 in MDA-MB-231

The lack of targeted therapy for triple-negative breast cancer (TNBC) is among the mainsprings of its poor prognosis. This study aimed to elucidate the role of the androgen receptor (AR) and its splice variant 7 (ARv7) in TNBC patients. Further, the molecular impact of their blockers, Enzalutamide and EPI-001, on the TNBC cell line MDA-MB-231 was investigated. Thereby, immunohistochemical expression of AR/ARv7 was assessed for TNBC Egyptian patients. Moreover, bioinformatics analysis of AR/ARv7 RNA status was carried out on TNBC patients from The Cancer Genome Atlas Breast Carcinoma project (TCGA-BRCA). Data from both groups was correlated with patients’ clinicopathological features. Besides, scratch wound healing assay and ELISA were employed to assess the effect of AR/ARv7 blockers on several metastasis markers in MDA-MB-231 cell line. In the Egyptian-TNBC patients, AR expression was associated with worse 7-year DFS (40.6±18.6%). In addition, ARv7 showed cytoplasmic and nuclear patterns, and both cytoplasmic and nuclear ARv7+ patients demonstrated a worse 7-year DFS (22.7±17.7% and 20±17.9%) and overall survival (63.6±14.5% and 40±21.8%). Importantly, 80% of the nuclear ARv7+ patients developed distant metastasis. The data of the TCGA-TNBC patients showed a tendency for poor outcomes in the high ARv7-expressing patients. Molecularly, in MDA-MB-231, both inhibitors modulated metastasis and epithelial to mesenchymal transition (EMT) markers ROCK1, ROCK2, c-Myc, E-cadherin and N-cadherin, with EPI-001 downregulating NF-ĸB level as well. We concluded that ARv7 indicated poor prognosis in the studied cohorts and that blocking of AR/ARv7 abated metastasis and key regulators of EMT in MDA-MB-231, at least in part by targeting ROCK/NF-ĸB/c-Myc axis.

Evaluation of breast-specific marker expression in metastatic breast cancers: Correlation with subtype switch.

This study evaluates the utility of breast specific markers in identifying breast cancer subtypes within metastatic settings. The subtype alteration in metastatic disease and its consequent impact on breast-specific marker expression is also examined. GATA-binding protein 3 (GATA3), mammaglobin (MMG), transcriptional repressor GATA binding 1 (TRSP1) and SRY-box transcription factor 10 (SOX10) expression were assessed in a large cohort of metastatic breast cancer (MBC) cases and correlated with the characteristics of both MBC and primary breast cancer (PBC). GATA3 was the most sensitive in MBC (83.1%), followed by TRPS1 (77.0%), MMG (58.5%) and SOX10 (7.1%). This trend was consistent in hormonal receptor (HR)+ and HR- MBC. Combining GATA3/TRPS1 yielded the highest detection rates in the overall cohort (90.1%) and HR+ MBC (97.1%), while TRSP1/MMG was most effective in HR- (76.2%) and TN (71.1%) MBC. Marker expression did not correlate with metastatic site, except SOX10 in lung metastases (P = 0.031). Subtype discordance between MBC and PBC occurred in 43 cases (24.4%), with GATA3 expression in HR- MBC significantly linked to subtype discordance (P = 0.005). Conversely, SOX10 expression was significantly associated with subtype concordance in HR- and TNBC (P ≤ 0.003). Despite a higher expression of GATA3 in all HR- cases, TRSP1 outperformed GATA3 in detecting concordant HR- cases (64.0% versus 38.5%). TRPS1 and SOX10 were expressed in more than 50% of concordant TNBC cases. The expression of breast-specific markers is mainly determined by the PBC subtype. GATA3 retains high sensitivity in HR+ cancers, even after HR loss during metastasis. TRPS1 and SOX10 are identified as valuable markers in TNBC metastasis.

P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.

The pro-inflammatory enzyme cyclooxygenase 2 (COX-2) has been known to impart metastatic property to cancer cells. However, blocking of COX-2 with nonsteroidal anti-inflammatory drugs or COX-2-specific inhibitors has failed in clinical trials due to adverse effects associated with their prolonged use. We have previously shown that extracellular ATP (eATP), a major component of the tumor microenvironment, enhances COX-2 expression several-fold, both in macrophages and in various cancer cells, by acting on purinergic (P2) receptors. In this study, we show that blocking of P2 receptors significantly reduced tumor growth in a mouse model of lymphoma. Tumors were induced in mice through subcutaneous injection of syngeneic EL4 lymphoma cells. Various P2 receptor antagonists were injected within the tumors after they were palpable. The broad-spectrum P2 receptor antagonist, suramin, P2X7 receptor-specific antagonist, oATP, P2Y6 receptor-specific antagonist, MRS 2578, and P2Y12 receptor-specific antagonist, AR-C 69931, all showed significant arrest in tumor growth. Both suramin and AR-C 69931-treated tumors showed strong reduction in COX-2 expression and modulation of various metastatic markers. Disaggregated cells from AR-C 69931-treated tumors, when injected intravenously in naïve mice, did not exhibit metastasis in various tissues which was observed in mice injected with cells from saline-treated tumors. Our results show that blocking of P2 receptors is a therapeutic alternative to inhibit COX-2 expression, and thereby, arrest tumor progression and metastasis.

N6‐methyladenosine reader YTHDF3‐mediated zinc finger protein 41 inhibits hepatocellular carcinoma progression by transcriptional repression of Snail

AbstractAdvanced metastasis of hepatocellular carcinoma (HCC) significantly contributes to high death rates among patients. The efficiency of targeted therapies and chemotherapeutic agents shows individual variability. Therefore, there is no effective treatment for advanced HCC. Zinc finger proteins (ZFPs) are known to be crucial in various tumors, especially on HCC. In our study, we verified that ZFP41 could suppress the progression and metastasis of HCC through in vitro and in vivo experiments. During the past years, N6‐methyladenine (m6A) regulation has also been increasingly reported in HCC. To investigate whether ZFP41 could be regulated via m6A methylation, our results showed that YTHDF3 bound to the mRNA of ZFP41 and degrade it. Subsequently, to further elucidate the function of ZFP41, we identified Snail, a well‐known oncogenic molecule, through RNA‐seq. As a canonical component in the epithelial‐to‐mesenchymal transition (EMT) pathway, Snail plays a pivotal role and is a critical marker for tumor invasion and metastasis. Our results showed ZFP41 could inhibit Snail and the EMT pathway through its transcriptional repression. In conclusion, our study revealed that ZFP41 is a potential prognostic element for patients with HCC, and targeting ZFP41 might be used for translational clinical applications as a promising therapeutic target.

Antimetastatic effect of nanodiamond-conjugated quercetin against colon cancer: an in vivo study.

Quercetin (Q) is a compound that can inhibit the growth of cancer cells in the colon; however, to do so, a high dose is needed, requiring a drug delivery system to target cancer endothelial cells directly. This study investigates the potency of nanodiamond-conjugated quercetin (NDQ) as an anticancer drug against colon cancer in Rattus norvegicus induced by N-methyl N-Nitrosourea (MNU). This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K-: treated by MNU); positive control (K+: treated by MNU and capecitabine); ND (treated by MNU and NDs); Q (treated by MNU and Q); and NDQ (treated by MNU and NDQ). To induce colon cancer in rats, MNU (10 mg/Kg BW) was administrated intrarectally three times per week for four weeks. The treatment of Q (40 mg/Kg BW) or NDQ (40 mg/Kg BW) was given intraperitoneally twice a week for 6 weeks. Cancer progression of all cohorts was evaluated by performing body and colon weight measurements, which involved the following: ELISA assay-specific to metastatic marker matrix metalloprotein-9 (MMP-9), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1 α (HIF1α), vascular endothelial growth factor, protein 53 (p53) and immunohistochemistry staining of Caspase-3 and Ki-67 proteins. Observation of cancer metastasis to the lung was also performed. NDQ significantly inhibited cancer aggressiveness by causing an increment in body weight gain and the growth rate-while reducing the colon weight compared to the K- group. Moreover, decreased levels of MMP-9, CEA, HIF-1α, and Ki67 and increased levels of p53 and Caspase-3 were more significant in the NDQ group than in the Q group. The lung tumor metastases in the NDQ group were fewer than in the K- group. NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.

Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis

BackgroundPrevious studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.MethodsWe compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.ResultsOur results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.ConclusionsOur study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

KRT14 as a potential prognostic marker for metastasis in metaplastic breast carcinoma

Metaplastic breast cancer (MBC) is an aggressive breast cancer subtype with poor prognosis. To elucidate underlying genomic aberrations driving MBC, we conducted integrated transcriptomic analyses of MBC tumors and basal breast cancer cell lines with various transitioning phases (xE = epithelial phase clone, xM = mesenchymal phase clone and xEM = Epithelial-mesenchymal clone). Differential gene expression analysis between MBC vs non-MBC samples as well as between epithelial-mesenchymal (xEM) transitioning cells vs parental cells revealed 12 commonly dysregulated genes intersected from both the datasets meditates pathways governing EMT, migration, proliferation and metastasis. Further investigation onto those genes based on multi-omics approaches that include survival analysis, correlated expression patterns and interactomics indicated KRT14 had a key role in promoting MBC aggression through Epithelial mesenchymal transition leading to metastasis. Moreover, NPR3 was found to be a possible link between KRT14 and EMT in metastasis. To our knowledge, this is the first evident gene expression study to investigate the potential association between the expression of KRT14 and NPR3 and metastasis in MBC, and their potential involvement in the epithelial-mesenchymal transition (EMT) process. These mechanistic and prognostic insights gained can lead to targeted therapeutics against this rare, refractory disease. Overall, this work highlights the effectiveness of integrated multi-omics in revealing gene expression pattern and predictive biomarkers for metaplastic breast cancer subtypes with poor prognosis.

P3.03H.05 AKAP12 Deficiency Leads to Blood-Brain Barrier Disruption and Serves as a Crucial Diagnostic Marker for Brain Metastasis in Lung Adenocarcinoma

P3.03H.05 AKAP12 Deficiency Leads to Blood-Brain Barrier Disruption and Serves as a Crucial Diagnostic Marker for Brain Metastasis in Lung Adenocarcinoma

ANKRD1 Promotes Breast Cancer Metastasis by Activating NF-κB-MAGE-A6 Pathway.

Early detection and surgical excision of tumors have helped improve the survival rate of patients with breast cancer. However, patients with metastatic cancer typically have a poor prognosis. In this study, we propose that ANKRD1 promotes metastasis of breast cancer. ANKRD1 was found to be highly expressed in the MDA-MB-231 and MDA-LM-2 highly metastatic breast cancer cell lines compared to the non-metastatic breast cancer cell lines (MCF-7, ZR-75-30, T47D) and normal breast cancer cells (MCF-10A). Furthermore, high-grade tumors showed increased levels of ANKRD1 compared to low-grade tumors. Both in vitro and in vivo functional studies demonstrated the essential role of ANKRD1 in cancer cell migration and invasion. The previous studies have suggested a significant role of NF-κB and MAGE-A6 in breast cancer metastasis, but the upstream regulators of this axis are not well characterized. Our study suggests that ANKRD1 promotes metastasis of breast cancer by activating NF-κB as well as MAGE-A6 signaling. Our findings show that ANKRD1 is a potential therapeutic target and a diagnostic marker for breast cancer metastasis.

Mitochondrial-related genes as prognostic and metastatic markers in breast cancer: insights from comprehensive analysis and clinical models.

Breast cancer (BC) constitutes a significant peril to global women's health. Contemporary research progressively suggests that mitochondrial dysfunction plays a pivotal role in both the inception and advancement of BC. However, investigations delving into the correlation between mitochondrial-related genes (MRGs) and the prognosis and metastasis of BC are still infrequent. Utilizing data from the TCGA database, we employed the "limma" R package for differential expression analysis. Subsequently, both univariate and multivariate Cox regression analyses were executed, alongside LASSO Cox regression analysis, to pinpoint prognostic MRGs and to further develop the prognostic model. External validation (GSE88770 merged GSE425680) and internal validation were further conducted. Our investigation delved into a broad spectrum of analyses that included functional enrichment, metabolic and immune characteristics, immunotherapy response prediction, intratumor heterogeneity (ITH), mutation, tumor mutational burden (TMB), microsatellite instability (MSI), cellular stemness, single-cell, and drug sensitivity analysis. We validated the protein and mRNA expressions of prognostic MRGs in tissues and cell lines through immunohistochemistry and qRT-PCR. Moreover, leveraging the GSE102484 dataset, we conducted differential gene expression analysis to identify MRGs related to metastasis, subsequently developing metastasis models via 10 distinct machine-learning algorithms and then selecting the best-performing model. The division between training and validation cohorts was set at 70% and 30%, respectively. A prognostic model was constructed by 9 prognostic MRGs, which were DCTPP1, FEZ1, KMO, NME3, CCR7, ISOC2, STAR, COMTD1, and ESR2. Patients within the high-risk group experienced more adverse outcomes than their counterparts in the low-risk group. The ROC curves and constructed nomogram showed that the model exhibited an excellent ability to predict overall survival (OS) for patients and the risk score was identified as an independent prognostic factor. The functional enrichment analysis showed a strong correlation between metabolic progression and MRGs. Additional research revealed that the discrepancies in outcomes between the two risk categories may be attributed to a variety of metabolic and immune characteristics, as well as differences in intratumor heterogeneity (ITH), tumor mutational burden (TMB), and cancer stemness indices. ITH, TIDE, and IPS analyses suggested that patients possessing a low-risk score may exhibit enhanced responsiveness to immunotherapy. Additionally, distant metastasis models were established by PDK4, NRF1, DCAF8, CHPT1, MARS2 and NAMPT. Among these, the XGBoost model showed the best predicting ability. In conclusion, MRGs significantly influence the prognosis and metastasis of BC. The development of dual clinical prediction models offers crucial insights for tailored and precise therapeutic strategies, and paves the way for exploring new avenues in understanding the pathogenesis of BC.

Cancer stem cells in meningiomas: novel insights and therapeutic implications.

Meningiomas (MGs), which arise from meningothelial cells of the dura mater, represent a significant proportion of primary tumours of the central nervous system (CNS). Despite advances in treatment, the management of malignant meningioma (MMG) remains challenging due to diagnostic, surgical, and resection limitations. Cancer stem cells (CSCs), a subpopulation within tumours capable of self-renewal and differentiation, are highlighted as key markers of tumour growth, metastasis, and treatment resistance. Identifying additional CSC-related markers enhances the precision of malignancy evaluations, enabling advancements in personalised medicine. The review discusses key CSC biomarkers that are associated with high levels of expression, aggressive tumour behaviour, and poor outcomes. Recent molecular research has identified CSC-related biomarkers, including Oct-4, Sox2, NANOG, and CD133, which help maintain cellular renewal, proliferation, and drug resistance in MGs. This study highlights new therapeutic strategies that could improve patient prognosis with more durable tumour regression. The use of combination therapies, such as hydroxyurea alongside diltiazem, suggests more efficient and effective MG management compared to monotherapy. Signalling pathways such as NOTCH and hedgehog also offer additional avenues for therapeutic development. CRISPR/Cas9 technology has also been employed to create meningioma models, uncovering pathways related to cell growth and proliferation. Since the efficacy of traditional therapies is limited in most cases due to resistance mechanisms in CSCs, further studies on the biology of CSCs are warranted to develop therapeutic interventions that are likely to be effective in MG. Consequently, improved diagnostic approaches may lead to personalised treatment plans tailored to the specific needs of each patient.

Research Progress on the Mechanism and Diagnostic Markers of Bone Metastasis in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a type of lung cancer with high malignant degree, rapid transformation, rapid invasion and metastasis, which is prone to early metastasis and poor prognosis. Bone metastases of SCLC occur in three stages: cancer cells proliferate at the primary site, break through local tissues, enter the blood circulation to form circulating tumor cells (CTCs), reach bone tissue through blood circulation, and take root and germinate to form new tumor sites with the support of the bone microenvironment. However, traditional imaging and pathology examinations have disadvantages such as low sensitivity, high cost and difficulty in implementation. Exploratory studies based on blood marker detection as screening and efficacy evaluation of SCLC bone metastases have been reported in recent years. By reviewing the molecular biological mechanism of SCLC bone metastasis formation, this paper found that conventional diagnostic methods such as imaging and pathological biopsy were inadequate in SCLC bone metastasis. The changes in hyaluronic acid, protein biomarkers, non-coding RNA, and biomarkers in liquid biopsy were earlier than the changes in imaging, which had the advantages of simple operation and good repeatability. It provides a new idea and method for the early diagnosis of SCLC bone metastasis, which is worthy of clinical application. .

Serum tumor markers: potential indicators for occult lymph node metastasis in clinical T1 − 2N0M0 small cell lung cancer patients

In their letter-to-the-editor entitled “Letter to the Editor: Incidence rate of occult lymph node metastasis in clinical T1 − 2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study”, Prof. Chen et al. provided insightful comments and suggestions on our original study. We appreciate the authors’ feedback and have conducted a preliminary exploration of the predictive value of serum tumor markers (TMs) for occult lymph node metastasis (OLM) in clinical T1 − 2N0M0 (cT1 − 2N0M0) small cell lung cancer (SCLC) patients. The results indicate that neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), and squamous cell carcinoma antigen (SCC) have potential predictive value for detecting OLM in cT1 − 2N0M0 SCLC patients. Additionally, further exploration and confirmation through prospective, large-scale studies with robust external validation are needed.

C-MET is an important marker for acid-driven metastasis and anti-immune in colorectal cancer

BackgroundThe tumor microenvironment plays an important role in cancer progression, especially acidic microenvironment which distinguish cancer from normal tissues and immune microenvironment. This study was the first to investigate whether acidic microenvironment affects colorectal metastasis through MET and the relationship between MET and immune microenvironment. MethodsWe used TCGA and GEO databases to predict MET expression, its relationship with clinical features, and biological function it mediated, and validated its expression with clinical data, as well as to verify that MET mediates acidic microenvironment-induced colorectal cancer metastasis by inducing EMT at the cellular and animal levels. The TCGA database was also used to analyze the relationship between MET and immune cells, immune checkpoints and TMB in colorectal cancer, and to predict its value in prognosis and immunological treatment and targeted therapy in pan-cancer. ResultsMET is highly expressed in colorectal cancer and is associated with metastasis and prognosis. Its biological function is mainly related to adhesion, cell cycle and fatty acid metabolism, and it can mediate acidic microenvironment to induce EMT and promote metastasis. According to immunoinfiltration analysis, MET expression is correlated with CD8 + T cells, DC, macrophages, Tregs, and TMB in CRC and were associated with the prognosis, immune checkpoint, and TMB of ACC, PRAD, LUAD respectively, in pan-cancer. ConclusionsMET is an important contributor to acid-driven colorectal cancer metastasis and participates in immune escape of colorectal cancer. It is of great significance for the prognosis and immunotherapy of colorectal cancer and some other cancers.

IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages

BackgroundTargeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown.MethodsIn this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified.ResultsIDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial–mesenchymal transition.ConclusionsOur findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.

Evaluation of peripheral blood inflammation indexes as prognostic markers for colorectal cancer metastasis

The aim of this study was to evaluate the prognostic value of peripheral blood inflammation indexes in patients with metastatic Colorectal Cancer (CRC) and to establish a predictive scoring system. A total of 324 CRC patients diagnosed through pathological examination from January 2017 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were included. The prognosis of patients with metastatic CRC was examined, and the correlation between IL-10 expression in pathological tissues and IL-10 expression in serum was analyzed. The results showed that the prognosis of CRC was poorer when metastasis occurred (P < 0.001). Additionally, IL-10 was highly expressed in the metastatic CRC group (P = 0.018), and the expression of IL-10 in pathological tissues of patients with metastatic CRC was positively correlated with the expression of IL-10 in serum (P = 0.037). The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-white blood cell ratio (LWR), aggregate index of systemic inflammation (AISI), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and interleukin-10 (IL-10) were calculated and determined by ROC curve. The critical values were 2.135, 3.735, 353.745, 0.265, 1.025, 52.975, 353.635, and 11.25, respectively. Inflammatory indexes with an AUC of more than 0.6 were selected, and each colorectal cancer patient with any of these risk factors was assigned a score of one. The 324 patients were then divided into two groups: 0–4 for the low-risk group and 4–8 for the high-risk group. The occurrence of distant metastases in the two groups was statistically analyzed. The results showed that the OS and PFS of the low-risk group were significantly superior to those of the high-risk group (P < 0.05). These findings indicate that NLR, LWR, AISI, MLR, SIRI, PNI, ALI, and IL-10 are risk factors for distant metastasis in CRC patients. Therefore, the prediction scores of these indexes can be used to effectively evaluate the prognosis of patients with metastatic CRC.

Tumor markers in non-small cell lung cancer spine metastasis: an assessment of prognosis and overall survival

PurposeThe identification of gene mutations in the modern medical workup of metastatic spine tumors has become more common but has not been highly utilized in surgical planning. Potential utility of these genetic markers as surrogates for cancer behavior in current prognosis scoring systems and overall survival (OS) remains underexplored in existing literature. This study seeks to investigate the association of frequently identified tumor markers, EGFR, ALK, and PD-L1, in metastatic non-small cell lung cancer (NSCLC) to the spine with Tokuhashi prognosis scoring and OS.MethodsPatients with NSCLC metastasis to spine were identified through chart review. EGFR, ALK, and PD-L1 wild type vs. mutant type were identified from targeted chemotherapy genetic testing. Multiple linear regression was performed to assess gene profile contributions to Tokuhashi score. Cox Proportional Hazards models were generated for each tumor marker to assess the relationship between each marker and OS.ResultsA total of 119 patients with NSCLC spine metastasis were identified. We employed a multiple linear regression analysis to investigate the influence of EGFR, ALK, and PD-L1 genotypes on the Tokuhashi score, revealing statistically significant relationships overall (p = 0.002). Individual genotype contributions include EGFR as a non-significant contributor (p = 0.269) and ALK and PD-L1 as significant contributors (p = 0.037 and p = 0.001 respectively). Overall survival was not significantly associated with tumor marker profiles through Kaplan-Meier analysis (p = 0.46) or by multivariable analysis (p = 0.108).ConclusionALK and PD-L1 were significantly associated with Tokuhashi score while EGFR was not. Tumor markers alone were not predictive of OS. These findings indicate that genetic markers found in NSCLC metastases to the spine may demonstrate prognostic value. Therefore, employing standard tumor markers could enhance the identification of appropriate surgical candidates, although they demonstrate limited effectiveness in predicting overall survival.

MRPL13 is a metastatic and prognostic marker of breast cancer: A silico analysis accompanied with experimental validation

BackgroundAlthough progress has been made in accurate diagnosis and targeted treatments, breast cancer (BC) patients with metastasis still present a grim prognosis. With the continuous emergence and development of new personalized and precision medicine targeting specific tumor biomarkers, there is an urgent need to find new metastatic and prognostic biomarkers for BC patients. MethodsWe were dedicated to identifying genes linked to metastasis and prognosis in breast cancer through a combination of in silico analysis and experimental validation. ResultsA total of 25 overlap differentially expressed genes were identified. Ten hub genes (namely MRPL13, CTR9, TCEB1, RPLP0, TIMM8B, METTL1, GOLT1B, PLK2, PARL and MANBA) were identified and confirmed. MRPL13, TCEB1 and GOLT1B were shown to be associated with the worse overall survival (OS) and were optionally chosen for further verification by western blot. Only MRPL13 was found associated with cell invasion, and the expression of MRPL13 in metastatic BC was significantly higher than in primary BC. ConclusionWe proposed MRPL13 could be a potential novel biomarker for the metastasis and prognosis of breast cancer.

Comparative profiling of whole-cell and exosome samples reveals protein signatures that stratify breast cancer subtypes

Identifying novel breast cancer biomarkers will improve patient stratification, enhance therapeutic outcomes, and help develop non-invasive diagnostics. We compared the proteomic profiles of whole-cell and exosomal samples of representative breast cancer cell subtypes to evaluate the potential of extracellular vesicles as non-invasive disease biomarkers in liquid biopsies. Overall, differentially-expressed proteins in whole-cell and exosome samples (which included markers for invasion, metastasis, angiogenesis, and drug resistance) effectively discriminated subtypes; furthermore, our results confirmed that the proteomic profile of exosomes reflects breast cancer cell-of-origin, which underscores their potential as disease biomarkers. Our study will contribute to identifying biomarkers that support breast cancer patient stratification and developing novel therapeutic strategies. We include an open, interactive web tool to explore the data as a molecular resource that can explain the role of these protein signatures in breast cancer classification.Graphical (A) We quantified proteomic profiles of breast cancer cells (BCCs) and breast cancer-derived exosomes (BCDEs) samples from four breast cancer cell lines representative of common breast cancer subtypes – Her2-positive (Her2, MDA-MB-453), Luminal A (LA, MCF7), Luminal B (LB, ZR-75), and triple-negative (TN, MDA-MB-231). (B) We independently performed four comparisons for BCCs and BCDEs, comparing each cell line against the remaining three. (C) We identified differentially-expressed proteins (DEPs) for BCCs and BCDEs, defined protein signatures, and functionally analyzed resulting networks. Through pathway inference analysis (PIA), we identified Kyoto Encyclopedia of genes and genomes (KEGG) subpaths and biological Gene Ontology (GO) terms that displayed differential activation. (D) We validated our proteomic signature using the Cancer Genome Atlas (TCGA) and the Cancer Proteome Atlas (TCPA) databases, verified that differentially-activated pathways in BCDEs caused a corresponding response in receptor cells, and confirmed that the BCDE proteomic signature reflects their cell-of-origin and identifies candidate disease biomarkers in liquid biopsies