Marker For Cancer Research Articles

Impact of metabolism-related markers on outcomes in ovarian cancer patients: Findings of the MITO16A/MaNGO-OV2 trial.

In ovarian cancer, expression of metabolism-related markers has been investigated in several studies focusing on individual markers; however, a parallel quantitative evaluation of markers mapping to distinct metabolic processes and their prognostic value in large patient cohorts is still lacking. Here, by using immunohistochemistry followed by digital pathology, we investigated the expression of several markers related to glycolysis including monocarboxylate transporter 1 and 4 (MCT1, MCT4), glutamine metabolism (glutaminase, GLS) and hypoxia/acidosis (carbonic anhydrase 9, CA IX) in tissue microarrays of > 300 patients recruited in the MITO16A clinical trial, which involved treatment of ovarian cancer patients with carboplatin/taxol plus bevacizumab. Regarding the prognostic impact of these markers, results indicate that GLS expression correlated with progression-free survival, but this effect disappeared when data were corrected for multiple testing. All other markers showed no correlation with clinical outcome. These results indicate marked heterogeneity of expression of metabolism-associated markers in ovarian cancer; however, there was a lack of association with clinical benefit after chemotherapy/anti-vascular endothelial growth factor treatment. Notwithstanding the lack of prognostic value, knowledge of the pattern of expression of these biomarkers in tumors can be useful for patient stratification purposes when new drugs targeting these metabolic pathways will be tested.

Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models

Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC.

Red Cell Distribution Width and the Early Detection of Ovarian Cancer

Ovarian Cancer is a leading cause of mortality and morbidity, lacking clinical manifestations and effective early diagnostic techniques. The majority of cases are diagnosed at later stages; however, asymptomatic screening is currently not recommended due to its low predictive value and invasive nature. Furthermore, the current CA-125 biomarker used to monitor Ovarian Cancer is elevated in other conditions, including endometriosis or pelvic inflammation. Red Cell Distribution Width (RDW) is a parameter measured in a complete blood count, measuring the range of variation in red blood cell size and heterogeneity of red blood cell volume. RDW levels positively correlate with Ovarian Cancer progression, additionally increased in Ovarian Cancer groups compared to benign ovarian tumour groups. RDW possesses high sensitivity in distinguishing between cancerous and benign ovarian tumours, in line with ideal screening method standards. RDW additionally shows potential as a diagnostic biomarker in combination with other blood parameters, such as hemoglobin. The hemoglobin-RDW ratio (HRR) acts as an independent predictor of Ovarian Cancer stage. RDW’s mechanism of action is not fully elucidated but can be associated with iron/folic acid deficiency, ineffective hematopoiesis caused by chronic inflammation, or inflammatory cytokines such as IL-1 and IL-17. High RDW levels additionally possess prognostic value, acting as an indicator of low cumulative overall survival and poor chemotherapy responses in various cancers. Further research is needed on RDW’s mechanism of action and its implication as a marker in female cancers, particularly Ovarian Cancer, to implement effective early screening techniques and reduce fatalities.

Bladder cancer immune-related markers: diagnosis, surveillance, and prognosis.

As an immune-related tumor type, bladder cancer has been attracting much attention in the study of its markers. In recent years, researchers have made rapid progress in the study of immune-related markers for bladder cancer. Studies have shown that immune-related markers play an important role in the diagnosis, prognosis assessment and treatment of bladder cancer. In addition, the detection of immune-related markers can also be used to evaluate the efficacy of immunotherapy and predict the treatment response of patients. Therefore, in depth study of the expression of immune-related markers in bladder cancer and their application in the clinic is of great significance and is expected to provide new breakthroughs for individualized treatment of bladder cancer. Future studies will focus more on how to detect immune-related markers with low cost and high accuracy, as well as develop new immunotherapeutic strategies to bring better therapeutic outcomes to bladder cancer patients.

Leap-Type Response of Redox/Photo-Active Lanthanide-Based Metal-Organic Frameworks for Early and Accurate Screening of Prostate Cancer.

The development of high-accuracy technologies to distinguish the quite tiny concentration change of tumor markers between negative and positive is of vital significance for early screening and diagnosis of cancers, but is still a great challenge for the conventional biosensors because of their "gradual" detection mode. Herein, a unique "leap-type" responsive lanthanide MOF-based biosensor (designated as Tb-CeMOF-X) with defect-mediated redox-/photo-activities is developed for precisely identifying acid phosphatase (ACP), an early pathological marker of prostate cancer (PCa) in serum. The engineered Tb-CeMOF-X probe achieves a bursting switch-on luminescence at the critical concentration of ACP (9 U ⋅ L-1), while keeping silent below this threshold, undergoing a qualitative signal change from "zero" to "one" between negative and positive indicators and thus significantly improving the identification precision. Significantly, such "leap-type" response performance can be further edited and amplified by rational defect engineering in the crystal structure to improve the accessibility of active centers, consequently maximizing the detection sensitivity toward ACP in the complex biological media. This study proposes the first paradigm for the development of "leap-type" biosensors with ultra-sensitive differentiation capability between negative and positive, and provides a potentially valuable tool for early and accurate screening of PCa.

Two step synthesis of fluorescent zirconia oxide amorphous nanosheets for highly sensitive detection of a cancer marker

This study has reported the first-ever fluorescent 2D amorphous zirconia nanosheets (ZrO2 NS) synthesis approach and their utilization for the detection of tyrosine. We have reported a novel yet simple approach to the synthesis approach by dissolving ZrCl4 in ethanol followed by the reduction with the use of sodium hydroxide. It is suggested that NaOH partially reduces Zr4+ and for Zr–OH conjugates finally forming ZrO2 sheet structure by Cl− templating due to the high affinity of reduced Zr towards oxygen. The as-synthesized 2D amorphous zirconia nanosheet suspension in ethanol resulted in a blue color fluorescence with an emission maximum of 430 nm. This nanosheet system shows a unique quenching property by tyrosine in both PBS buffer and human blood serum. This system was utilized to develop a fluorometric sensing platform for a cancer biomarker, tyrosine. The system showed firm results in 1–100 nM range with a LOD of 14.9 nM in human blood serum and 8.4 nM in PBS. This study has opened a new insight into utilizing 2D amorphous zirconia nanostructures in a novel way and also it creates a platform for using the 2D amorphous NS as a biosensor to detect cancer markers in the medical and biomedicine fields too.

A Proton Pump Inhibitor Independently Elevates Gastrin Levels as a Marker for Metachronous Gastric Cancer After Endoscopic Submucosal Dissection.

Background and Objective: Serum markers such as gastrin and pepsinogen are useful for stratifying gastric cancer risk. However, their utility in predicting metachronous gastric cancer after endoscopic submucosal dissection (ESD) in patients with gastric cancer after Helicobacter pylori eradication (GCAE) is unclear. This study aimed to clarify predictive factors for metachronous gastric cancer after ESD with a focus on serum markers. Methods: A retrospective analysis was conducted on 197 patients with 224 GCAE lesions who underwent ESD at Hiroshima University Hospital between April 2010 and December 2019. In total, 63 patients with 74 differentiated-type lesions were classified into metachronous gastric cancer (MG) and non-metachronous gastric cancer (NMG) groups, excluding proton pump inhibitor (PPI) users, female patients, and undifferentiated-type cases. The predictive value of serum markers was assessed using ROC curve analysis, and their association with carcinogenesis was evaluated using multiple logistic regression. Furthermore, the incidence of MG was compared between long-term PPI users and non-users. Results: ROC analysis revealed that serum gastrin had the highest discriminative ability for MG (AUC 0.77, cut-off 99 pg/mL, sensitivity 61.6%, and specificity 80.0%). Severe mucosal atrophy and high gastrin levels were significantly more common in the MG group and were independent predictors (p < 0.01). Although serum gastrin levels were significantly elevated in PPI users, no increased risk of MG was observed. Conclusions: In addition to severe mucosal atrophy, PPI-independent elevated serum gastrin levels may be associated with an increased risk of MG after ESD. Serum gastrin may serve as a valuable marker for post-ESD cancer surveillance in GCAE patients.

Evaluation of Fluctuations of BRAF Gene Expression and its Polymorphism at rs1267623 in Colorectal Cancer.

Molecular markers in Colorectal Cancer (CRC) are needed for more accurate classification and personalized treatment. In this way, we investigated the effects of the BRAF gene on clinical outcomes of its expression fluctuations and its polymorphism at rs1267623 in CRC. In this study, 36.36 percent of patients with CRC were women, and 63.63 percent were men. After the pathology department confirmed the tumor of the samples, the stage and grade of the tumor were determined according to the TNM system. Real-time PCR was used to check the expression of the BRAF gene in tumor and non-tumor tissues, and its polymorphism in rs1267623 was also checked using the Tetra-ARMs PCR technique. The expression of BRAF in tumor tissues was significantly higher than in non-tumoral tissues (P = 0.001), indicating an upregulation of BRAF gene expression in tumoral tissues. The user's text is empty. Furthermore, there was a significant correlation between BRAF expression and tumor stage (P = 0.001), as well as tumor grade (P = 0.003). However, no significant link was found between lymph node metastasis and distant metastasis of BRAF gene expression (P = 0.3). Additionally, no mutation was detected in the investigation of rs1267623 polymorphism. The BRAF gene was upregulated in tumoral tissues. Remarkably, no mutation was found in the rs1267623 polymorphism. As a result, this gene can be used as a biomarker in the diagnosis and treatment of CRC.

Circulating necroptosis markers in chronic pancreatitis and pancreatic cancer: associations with diagnosis and prognostic factors

ObjectivesNecroptosis, a programmed inflammatory cell death, is implicated in the pathogenesis of pancreatitis and its potential progression to pancreatic ductal adenocarcinoma (PDAC), but its role remains unclear. We compared plasma levels of necroptosis-related markers - mixed lineage kinase domain-like protein (MLKL), interleukin (IL)-33, and its soluble receptor (sST2)- in patients with chronic pancreatitis (CP), PDAC, and healthy controls (HC), to explore their diagnostic and prognostic significance. MethodsPlasma was collected from patients pre-procedurally (PDAC, n=82; CP, n=25) and from HC (n=39), and studied by ELISA. Clinical and routine laboratory data were collected, and pancreas was defined as soft or non-soft based on intraoperative or imaging findings. Mann-Whitney U test, Spearman correlation coefficients, ROC analysis were used for statistical analysis. ResultsPlasma MLKL was lower in patients with CP than in other groups (p<0.001) and PDAC patients treated with upfront surgery (PDACUS, n=65) had lower MLKL than HC (p=0.035). MLKL differentiated CP from PDACUS (AUC 0.83, p<0.001). sST2 levels were significantly lower in HC than in other groups (p<0.001) and in PDAC patients with a soft pancreas compared with non-soft (p<0.005). In Lewis antigen positive PDACUS (n=59), sST2 had positive correlations with CA19-9 measured concurrently and after 1 month, and with CEA measured after 1 or 6 months. ConclusionsCirculating levels of MLKL are lower in patients with CP than PDAC. Elevated sST2 levels are associated with pancreatic diseases. Further studies are required to show whether MLKL and sST2 could be useful biomarkers in evaluating pancreatic diseases.

AI-based tumor-infiltrating lymphocytes scoring system for assessing HCC prognosis in patients undergoing liver resection

Background & AimsTumor-infiltrating lymphocytes (TILs), particularly CD8+ TILs, are key prognostic markers in many cancers. However, their prognostic value in hepatocellular carcinoma (HCC) remains controversial, with different evidence. Given the heterogeneous outcomes in HCC patients undergoing liver resection, this study aims to develop an AI-based system to quantify CD8+ TILs and assess their prognostic value for HCC patients. MethodsWe conducted a retrospective multicenter study on patients undergoing liver resection across three cohorts (N=514). We trained a deep neural network and a random forest model to segment tumor regions and locate CD8+ TILs in H&E and CD8-stained whole slide images (WSIs). We quantified CD8+ TIL density and established an Automated CD8+ Tumor-infiltrating Lymphocyte Scoring (ATLS-8) system to assess its prognostic value. ResultsIn discovery cohort, the 5-year overall survival (OS) rates were 34.05% for ATLS-8 low-score and 65.03% for ATLS-8 high-score groups (HR 2.40; 95% CI, 1.37–4.19; P = 0.015). These findings were confirmed in validation cohort 1, which had 5-year OS rates of 28.57% and 68.73% (HR 3.38; 95% CI, 1.27–9.02; P = 0.0098), and validation cohort 2, which had 59.26% and 81.48% (HR 2.74; 95% CI, 1.05–7.15; P = 0.031). ATLS-8 improved prognostic model based on clinical variables (C-index 0.770 vs. 0.757; 0.769 vs. 0.727; 0.712 vs. 0.642 in three cohorts). ConclusionWe developed an automated system using CD8-stained WSIs to assess immune infiltration (ATLS-8). In HCC patients undergoing resection, higher CD8+ TIL density correlates with better OS, as per ATLS-8 assessment. This system is a promising tool for advancing clinical immune microenvironment assessment and outcome prediction. Impact and implicationCD8+ TILs have been identified as a prognostic factor associated with many cancers. In this study, CD8+ TILs were identified as an independent prognostic factor for OS in patients with hepatocellular carcinoma who undergoing liver resection. Therefore, ATLS-8, a novel digital biomarker based on WSI-level CD8+ TILs, could play an important role in the prognostic assessment of HCC patients and could be integrated into clinicopathological models to participate in the decision-making and prognostic assessment of patients. The scoring system combined with artificial intelligence is essential for automated, quantitative, WSI- level assessment of TILs, which can be widely applied to quantify the immune profile of multi-cancer disease types with the discussion of subsequent immunotherapy. Clinical trial numberThis is a retrospective study and does not require a clinical trial number.

A cross-cohort study identifies potential oral microbial markers for esophageal squamous cell cancer

A cross-cohort study identifies potential oral microbial markers for esophageal squamous cell cancer

Establishing Medical Intelligence-Leveraging Fast Healthcare Interoperability Resources to Improve Clinical Management: Retrospective Cohort and Clinical Implementation Study.

FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. This study aimed to design and implement a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. A Python package for the use of multimodal FHIR data (FHIRPACK [FHIR Python Analysis Conversion Kit]) was developed and pioneered in 5 real-world clinical use cases, that is, myocardial infarction, stroke, diabetes, sepsis, and prostate cancer. Patients were identified based on the ICD-10 (International Classification of Diseases, Tenth Revision) codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. For 2022, a total of 1,302,988 patient encounters were analyzed. (1) Myocardial infarction: in 72.7% (261/359) of cases, medication regimens fulfilled guideline recommendations. (2) Stroke: out of 1277 patients, 165 received thrombolysis and 108 thrombectomy. (3) Diabetes: in 443,866 serum glucose and 16,180 glycated hemoglobin A1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (13,887/35,494). Among those with dysglycemia, diagnosis was coded in 44.2% (6138/13,887) of the patients. (4) Sepsis: In 1803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (773/2672, 28.9%) and piperacillin and tazobactam was the primarily prescribed antibiotic (593/1593, 37.2%). (5) PC: out of 54, three patients who received radical prostatectomy were identified as cases with prostate-specific antigen persistence or biochemical recurrence. Leveraging FHIR data through large-scale analytics can enhance health care quality and improve patient outcomes across 5 clinical specialties. We identified (1) patients with sepsis requiring less broad antibiotic therapy, (2) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, (3) patients who had a stroke with longer than recommended times to intervention, (4) patients with hyperglycemia who could benefit from specialist referral, and (5) patients with PC with early increases in cancer markers.

Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Enhances Natural Killer Cell Cytotoxicity in HER2-Overexpressing Ovarian Cancer.

Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer. Firstly, we screened the HER2 expression in three ovarian cancer cell lines and eight ovarian cancer patient-derived tumor xenograft (PDTX) samples. Then, immunohistochemistry and silver in situ hybridization (SISH) were performed following clinical criteria. HER2-overexpressing cells exhibited the highest sensitivity to samfenet compared with low-HER2-expressing cells. In addition, the combination of samfenet with natural killer (NK) cells resulted in significantly enhanced sensitivity to HER2-overexpressing cells and showed a significant antitumor effect on PDTX mice compared with monotherapy. It is known that anti-HER2-humanized IgG1 monoclonal antibodies, including trastuzumab, induce antibody-dependent cellular cytotoxicity (ADCC). Consequently, the combination of samfenet with NK cells demonstrated NK cell-mediated ADCC, as confirmed using an in vitro NK cytotoxicity assay and in vivo antitumor efficacy. A transferase dUTP nick end labeling (TUNEL) assay using xenografted tumors further supported the ADCC effects based on the increase in the number of apoptotic cells in the combination group. Furthermore, high HER2 expression was associated with shorter progression-free survival and overall survival based on public mRNA expression data. In this study, we demonstrated that the combination of samfenet and NK cell therapy could be a promising treatment strategy for patients with HER2-overexpressing ovarian cancer, through ADCC effects. Therefore, this study supports a rationale for further clinical studies of the combination of samfenet and NK cells as a therapy for patients with HER2-overexpressing ovarian cancer.

SOX17 Expression in Mesotheliomas and Benign Mesothelial Proliferations: Implications for Differential Diagnosis With Gynecologic Carcinomas.

SOX17 has recently emerged as a novel immunohistochemical marker for cancers of endometrial and ovarian origin with improved specificity compared with the widely used Mullerian marker PAX8. However, evaluation of SOX17 in benign and malignant peritoneal mesothelial proliferations remains limited, and these may mimic gynecologic carcinomas, particularly on small biopsies. We evaluated SOX17 and PAX8 expression in 20 benign mesothelial lesions (5 adenomatoid tumors, 5 well-differentiated papillary mesothelial tumors, and 10 peritoneal inclusion cysts) and 16 epithelioid peritoneal mesotheliomas. The 17 female and 3 male patients with benign mesothelial lesions ranged from 20 to 80yr (median: 56.5yr), while the 9 females and 7 males with mesothelioma ranged from 47 to 85yr (median: 57.5yr). SOX17 was positive in 5 (25%) benign lesions (2 adenomatoid tumors, 3 peritoneal inclusion cysts) and 2 (13%) mesotheliomas, while PAX8 stained 8 (40%) benign lesions (1 adenomatoid tumor, 1 well-differentiated papillary mesothelial tumor, 6 peritoneal inclusion cysts), and 2 (13%) mesotheliomas. Results for the 2 stains showed incomplete concordance, with agreement in 15 (75%) benign proliferations and 14 (88%) mesotheliomas. Our findings suggest that SOX17 positivity alone is insufficient to confirm a diagnosis of gynecologic carcinoma over a mesothelial proliferation and pathologists should exercise caution when these entities are diagnostic considerations.

Reflection mode polarimetry guides laser mass spectrometry to diagnostically important regions of human breast cancer tissue

To enhance the clinical utility of mass spectrometry (MS), lengthy dwell times on less informative regions of patient specimens (e.g., adipose tissue in breast) must be minimized. Additionally, a promising variant of MS known as picosecond infrared laser MS (PIRL-MS) faces further challenges, namely, lipid contamination when probing adipose tissue. Here we demonstrate on several thick non-sectioned resected human breast specimens (healthy and malignant) that reflection-mode polarimetric imaging can robustly guide PIRL-MS toward regions devoid of significant fat content to (1) avoid signal contamination and (2) shorten overall MS analysis times. Through polarimetric targeting of non-fat regions, PIRL-MS sampling revealed feature-rich spectral signatures including several known breast cancer markers. Polarimetric guidance mapping was enabled by circular degree-of-polarization (DOP) imaging via both Stokes and Mueller matrix polarimetry. These results suggest a potential synergistic hybrid approach employing polarimetry as a wide-field-imaging guidance tool to optimize efficient probing of tissue molecular content using MS.

Diagnostic value of salivary tumor markers in breast, lung and ovarian cancer

Background: Breast and ovarian cancers, the most common cancers in women are expected to rise in the next decade. Ovarian cancer is a "silent killer" because of its heterogeneity and asymptomatic early stage. It is currently the fifth most common cause of cancer-related deaths in women, making it the most deadly gynecological malignancy. Objective: To determine the diagnostic value of salivary tumor markers in breast, Lung and Ovarian cancer Methods: A cross-sectional study was conducted at General Hospital Lahore, Pakistan, which was performed between September 2023 to July 2024, The total number of patients in our study were 120. The number of female patients in our study were 120. For all patients, we did diagnostic tests, blood test and Biopsies. We also took the stages of cancer for breast, lung and ovary. We took the symptoms and causes for all patients. We excluded children and pregnant women in our study. Data was tabulated and analyzed by SPSS version 27. Result: In a current study total 120 patients were enrolled. The minimum age of patients were 47 years and the maximum age of the patients were 63 years. The mean age were 54.15±5.354 years. The minimum BMI (Kg/m2) of patients were 31 years and the maximum BMI of the patients were 39 years. The mean BMI were 34.60±2.468 (Kg/m2). The frequency of breast cancer in situ were 3 patients and nill patients were 75 and its percentage were 62%. The breast cancer stage I were present in 12 patients , stage II were 24 patients and Stage III were 6 Patients. P-value were less than 0.04. The frequency of nil patients number in lung cancer were 90 and its percentage were 75%. The frequency of stage I lung cancer were 6 , stage II were 12, stage III were 6 and stage IV were 6 and its percentage were 5%. P-value were &lt;0.02. The frequency of metastasis PM1 in the lung were 5 and in the ovary were 2. Over all P-Value in our study were &lt; 0.05. Conclusion: Saliva would be an excellent diagnostic tool to help cancer patients live longer and with better quality of life. Saliva-omics prove to be a good diagnostic tool for ovarian cancer at early stage. In our study Metastasis PM1 were more in lung as compared to breast and ovary

Impact of Pre-operative Lymphocyte and Albumin Combination on Adjuvant Chemotherapy and Prognosis of Gastric Cancer.

Cancer-associated systemic inflammatory response is a pivotal indicator of tumor progression and prognosis in various cancers. "Lymphocyte × albumin (LA)" is a prognostic inflammatory marker in rectal cancer. This study examined the correlation between LA, complete adjuvant chemotherapy (ACT), and prognosis in patients with gastric cancer (GC) who underwent radical gastrectomy. We retrospectively evaluated 108 patients with stage II/III GC who underwent radical gastrectomy at our institute between January 2015 and December 2021. Survival was assessed using Kaplan-Meier and Cox regression analyses. Factors associated with complete ACT were identified using logistic regression analysis. Of the 108 patients with GC, 60 (55.6%) and 41 (38.0%) initiated and completed ACT, respectively. In multivariate analysis, the pre-operative LA was an independent factor for complete ACT [hazard ratio (HR)=0.35, 95% confidence interval (CI)=0.121-0.995; p=0.049]. In addition, age, pre-operative creatinine clearance, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score, and poor overall survival were significantly associated with low LA (<7,474). LA was an independent prognostic factor for overall survival in univariate analysis (HR=2.29, 95%CI=1.020-5.145; p=0.045) but not in multivariate analysis (HR=2.00, 95%CI=0.882-4.552; p=0.097). Pre-operative LA is a useful marker for predicting complete ACT and prognosis of patients with GC following radical gastrectomy.

Deconvolution of cell-type-associated markers predictive of response to neoadjuvant radiotherapy

Tumor microenvironent contains prognostic molecular markers and therapeutic targets from different cellular sources, which are still not fully revealed in the resistance and recurrence after radiotherapy for rectal cancer. By integrating the scRNA-seq data, we deconvoluted the bulk transcriptomics of rectal cancer collected before preoperative neoadjuvant radiotherapy (nRT) into fractions and gene expression of the six cell types. The inferred cell-type-associated DEGs, abbreviated as caDEGs, of myeloid and stromal cells were enriched for overlapping yet unique biological processes including immunity, angiogenesis, and metabolism, respectively. Ecotyper analysis indicates that the caDEGs reflects cell states and ecotypes in association with nRT response. By mapping the caDEGs onto the context-free and newly built ligand-receptor and collagen-integrin lists from scRNA-Seq data, respectively, we inferred 297 cell-type-specific trans- and/or cis-collagen-integrin and 219 heterotypic ligand-receptor interactions potentially associated with nRT response, including interactions between stromal-associated COL1A2/COL6A1/COL6A2 and stromal or CMS1-associated ITGA1/B1, between epithelial-associated JAG1 and stromal-associated NOTCHs, between CMS2 epithelial-associated CCL15 and proliferating myeloid-associated CCR1, between myeloid-associated CCL4/CD86 and lymphatic endothelial-associated ACKR2, and between myeloid-associated TNFS13B and B cell-associated TNFRSF13B/C, etc. Intriguingly, results suggest a greater number of down-regulated cell-type-related markers in resistant cancers to nRT. Favorable myeloid-associated CD14, epithelial-associated DYM, stromal-associated COL1A2 and COL3A1, and unfavorable epithelial-associated CELSR3 and KCNH8 markers were inferred at least from two independent nCRT datasets of GSE119409, GSE35452, and GSE45404. The results provide insights into roles of the stromal and immune cells beside epithelial cells in resistance to radiotherapy for rectal cancers. The proposed approach can be applicable to other diseases as well. Codes and additional data are available at https://github.com/Xueling21/rectalNRT_deconv.

Clinically aggressive follicular cell-derived thyroid carcinoma: A comprehensive series with histomolecular characterization and discovery of novel gene fusions

Thyroid cancer rates are increasing, mostly with a good prognosis and less than 2 % of cases are more aggressive. Recent efforts focus on understanding molecular events predicting tumor aggressiveness and treatment targets in advanced thyroid cancer. This study concerned 57 patients with aggressive metastatic, and/or radioiodine-refractory thyroid carcinomas, excluding anaplastic cases. Molecular profiling, including next-generation sequencing and RNA sequencing, was conducted to dissect the complex molecular landscape of these aggressive tumors. Histopathological analysis indicated that papillary carcinomas and high-grade thyroid carcinomas were predominant. The molecular analysis revealed a spectrum of mutations, with prevalent occurrences of BRAF V600E, TERT promoter, and RAS mutations. RNA sequencing identified ten gene fusions, such as NTRK and RET fusions. Three novel fusions were discovered: UGGT1::TERT, BTBD9::TERT, and TG::IGF1R, potentially driving aggressive behavior. UGGT1::TERT was linked to radioiodine-refractory tall cell PTC, BTBD9::TERT to high-grade follicular PTC, and TG::IGF1R to oncocytic carcinoma. These findings underscore the importance of TERT alterations in aggressive phenotypes and offer insights into molecular mechanisms guiding targeted therapies. Further research is necessary to confirm their significance as diagnostic and prognostic markers in thyroid cancer.

Expression of CD44 in Triple Negative Breast Cancer and its Correlation with Prognostic Parameters

Background: The study aims to evaluate CD44 expression as a cancer stem cell marker in Triple-negative breast cancer (TNBC) and its correlation with prognostic parameters. Evaluation of CD44 immunoexpression in TNBC is vital for understanding tumour aggressiveness and determining its prognostic value. Methods: A hospital based cross sectional study of 50 cases of primary triple negative breast cancer patients. The tissue sections were subjected to immunohistochemical examination using CD44 antigen marker. The proportion and intensity of CD44 immunostaining was assessed and correlation with prognostic markers such as histological grade, tumor size and nodal status. Results: CD44 expression was observed in 40% of the total cases with a statistically significant association with histological grade (p-value= 0.002). Higher CD44 expression was noticed with increasing tumour grade. However, no statistical significance was observed with respect to tumour size and nodal status. Conclusion: The study suggests that CD44 immunoexpression may serve as a surrogate marker of BCSCs and may hold prognostic value in TNBC patients. However, further studies on larger samples are required to fully understand its role.