Cancer Subtypes Research Articles

Nanoconjugate Carrying pH-Responsive Transferrin Receptor-Targeted Hesperetin Triggers Triple-Negative Breast Cancer Cell Death through Oxidative Attack and Assemblage of Pro-Apoptotic Proteins.

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of breast cancer due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance to standard current treatments. Hesperetin (HSP), a natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but its hydrophobicity limits its clinical development. The present study reports the fabrication of a biocompatible and pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic-co-glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its in vitro and in vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and 1H NMR spectroscopy. The stability and in vitro release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of in vitro cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. In vivo tumor regression and host survival studies were executed in Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. The drug uptake of highly stable PLGA-HSP-TF NPs was accomplished effectively in MDA-MB-231 cells and showed the pH-dependent intracellular release of HSP, which generated excessive intracellular reactive oxygen species (ROS) that led to oxidative assault to the TNBC cells. This elevated ROS dropped the mitochondrial membrane potential and triggered apoptosis-mediated cell death by arresting the cell cycle at the G0/G1 phase. Furthermore, PLGA-HSP-TF NPs unveiled significant in vivo Ehrlich ascites carcinoma regression and host survival compared to free HSP with minimum toxicity at a minimum dose of 20 mg/kg body weight. The study divulges that PLGA-HSP-TF NPs may be an astounding anticancer nanocandidate for aggressive triple-negative breast cancer therapy.

Case report: A golden tail of immunotherapy: significant tail effect in a chemotherapy-resistant advanced pulmonary sarcomatoid carcinoma patient treated by Sintilimab combined with Anlotinib

Tail effect is a unique phenomenon in immunotherapy characterized by the prolonged maintenance of therapeutic efficacy. It can be observable even after treatment cessation. Immunotherapy has gradually become a vital regimen for the treatment of advanced lung cancer patients, among which immune-combined therapies based on immune checkpoint inhibitors (ICIs) have been applied clinically and demonstrates considerable clinical efficacy. In this case report, the patient was pathologically diagnosed with pulmonary sarcomatoid carcinoma (PSC), a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC) known for its poor prognosis due to high invasiveness and metastatic potential. After developing resistance to chemotherapy, the patient was treated with a combined regimen of sintilimab and anlotinib, leading to initial clinical improvement. Following just three cycles of this regimen, treatment was discontinued, and the patient was discharged. Remarkably, over the subsequent months, the patient exhibited a significant tail effect, evidenced by sustained therapeutic stability, continuous tumor regression, stable low levels of serum carcinoembryonic antigen (CEA), and further improvement in clinical symptoms. Tail effect is a golden tail of immunotherapy. This case illustrates that the tail effect of immunotherapy can offer substantial survival benefits for patients with unresectable advanced lung cancer who have failed chemotherapy.

BreCML: identifying breast cancer cell state in scRNA-seq via machine learning

Breast cancer is a prevalent malignancy and one of the leading causes of cancer-related mortality among women worldwide. This disease typically manifests through the abnormal proliferation and dissemination of malignant cells within breast tissue. Current diagnostic and therapeutic strategies face significant challenges in accurately identifying and localizing specific subtypes of breast cancer. In this study, we developed a novel machine learning-based predictor, BreCML, designed to accurately classify subpopulations of breast cancer cells and their associated marker genes. BreCML exhibits outstanding predictive performance, achieving an accuracy of 98.92% on the training dataset. Utilizing the XGBoost algorithm, BreCML demonstrates superior accuracy (98.67%), precision (99.15%), recall (99.49%), and F1-score (99.79%) on the test dataset. Through the application of machine learning and feature selection techniques, BreCML successfully identified new key genes. This predictor not only serves as a powerful tool for assessing breast cancer cellular status but also offers a rapid and efficient means to uncover potential biomarkers, providing critical insights for precision medicine and therapeutic strategies.

The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer.

Breast cancer, one of the most common forms of cancer, is associated with the highest cancer-related mortality among women worldwide. In comparison to other types of breast cancer, patients diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst outcome because current therapies do not produce long-lasting responses. Hence, innovative therapies that produce persisting responses are a critical need. We previously discovered that hyperactivating purinergic receptors (P2RXs) by increasing extracellular adenosine triphosphate (eATP) concentrations enhances TNBC cell lines' response to chemotherapy. Heparan sulfate inhibits multiple extracellular ATPases, so it is a molecule of interest in this regard. In turn, heparanase degrades polysulfated polysaccharide heparan sulfate. Importantly, previous work suggests that breast cancer and other cancers express heparanase at high levels. Hence, as heparan sulfate can inhibit extracellular ATPases to facilitate eATP accumulation, it may intensify responses to chemotherapy. We postulated that heparanase inhibitors would exacerbate chemotherapy-induced decreases in TNBC cell viability by increasing heparan sulfate in the cellular microenvironment and hence, augmenting eATP. We treated TNBC cell lines MDA-MB 231, Hs 578t, and MDA-MB 468 and non-tumorigenic immortal mammary epithelial MCF-10A cells with paclitaxel (cytotoxic chemotherapeutic) with or without the heparanase inhibitor OGT 2115 and/or supplemental heparan sulfate. We evaluated cell viability and the release of eATP. Also, we compared the expression of heparanase protein in cell lines and tissues by immunoblot and immunohistochemistry, respectively. In addition, we examined breast-cancer-initiating cell populations using tumorsphere formation efficiency assays on treated cells. We found that combining heparanase inhibitor OGT 2115 with chemotherapy decreased TNBC cell viability and tumorsphere formation through increases in eATP and activation of purinergic receptors as compared to TNBC cells treated with single-agent paclitaxel. Our data shows that by preventing heparan sulfate breakdown, heparanase inhibitors make TNBC cells more susceptible to chemotherapy by enhancing eATP concentrations.

LW-MorphCNN: a lightweight morphological attention-based subtype classification network for lung cancer

Abstract Lung cancer is generally considered one of the most deadly cancers globally. If it can be identified early and diagnosed correctly, the survival probability of patients can be significantly improved. In this process, histopathological examination is a commonly used method for diagnosing and detecting lung cancer. It is crucial to accurately identify lung cancer subtypes from histopathological images, as this helps doctors formulate effective treatment plans. However, the visual inspection in histopathological diagnosis requires a large amount of time and also depends on the subjective perception of clinicians. Therefore, this paper proposes a lightweight lung cancer subtype classification network based on morphological attention (LW-MorphCNN), which is used to automatically classify the histopathological images of benign lung tumors, ADC (adenocarcinoma), and SCC (squamous cell carcinoma) provided in the public dataset LC25000 (Lung and Colon). This paper takes histopathological images as input and conducts a comparative analysis with classic networks such as VGG16, VGG19, DenseNet121, and ResNet50, as well as existing classification methods proposed in the same work. The network proposed in this paper is superior to other networks in terms of parameter quantity and performance, with an accuracy rate and F1 - score reaching 99.47% and 99.44% respectively. Clinicians can install the provided LW-MorphCNN in the hospital to confirm the diagnosis results.

Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.

In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR2) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer. After a median of 11.8 years of follow-up, 531 cases of primary liver cancer were observed, of which 366 occurred in males and 165 occurred in females. Total testosterone and SHBG were shown to be positively associated with liver cancer risk in both males and females (Total testosterone HR2: 3.42, 95% CI:2.42-4.84 and 1.29, 0.97-1.72, respectively; SHBG HR2: 5.44, 4.42-6.68 and 1.52, 1.09-2.12, respectively). However, free testosterone was inversely associated with primary liver cancer in males (HR2: 0.42, 0.32-0.55) and no association was observed in females. When analyses compared two main liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), there was evidence of heterogeneity; associations for total testosterone and SHBG concentrations were only positively associated with HCC in both males (HR2: 3.56, 2.65-4.79 and 7.72, 6.12-9.73, respectively) and females (HR2: 1.65, 1.20-2.27 and 6.74, 3.93-11.5, respectively) but not with ICC. Further research understanding the mechanisms of how sex-steroids may influence liver cancer risk is needed.

Single-cell sequencing unveils mitophagy-related prognostic model for triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking hormone receptors and HER2 expression, leading to limited treatment options and poor prognosis. Mitophagy, a selective autophagy process targeting damaged mitochondria, plays a complex role in cancer progression, yet its prognostic significance in TNBC is not well understood.MethodsThis study utilized single-cell RNA sequencing data from the TCGA and GEO databases to identify mitophagy-related genes (MRGs) associated with TNBC. A prognostic model was developed using univariate Cox analysis and LASSO regression. The model was validated across multiple independent cohorts, and correlations between MRG expression, immune infiltration, and drug sensitivity were explored.ResultsNine key MRGs were identified and used to stratify TNBC patients into high-risk and low-risk groups, with the high-risk group showing significantly worse survival outcomes. The model demonstrated strong predictive accuracy across various datasets. Additionally, the study revealed a correlation between higher MRG expression levels and increased immune cell infiltration, as well as potential responsiveness to specific chemotherapeutic agents.ConclusionThe mitophagy-related prognostic model offers a novel method for predicting outcomes in TNBC patients and highlights the role of mitophagy in influencing the tumor microenvironment, with potential applications in personalized treatment strategies.

Menopausal status-dependent alterations in the transcript levels of genes encoding ERα, ERβ, PR and HER2 in breast tumors with different receptor status.

Breast cancer has distinct causes and prognoses in patients with premenopausal and postmenopausal status. The expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are analyzed by immunohistochemistry (IHC) to classify molecular subtypes of breast cancer among which large differences in prognosis exist. The mRNA expression of ESR1 (encoding ERα), ESR2 (encoding ERβ), PGR (encoding PR), and ERBB2 (encoding HER2) was analyzed based on menopausal status (pre- vs post-menopausal) in tumors from breast cancer patients with different receptor status, in R programming environment, using transcriptomics data from TCGA-BRCA project. In ER-positive or PR-positive or HER2-negative breast tumors, ESR1 transcript levels were found to be higher in tumors from postmenopausal women than those from premenopausal women; in contrast, ESR2 transcript levels were lower in tumors from postmenopausal women than those from premenopausal women. Furthermore, PGR mRNA expression was lower in breast tumors from postmenopausal women than those from premenopausal women, only in those with ER + or PR + status. The expression of these genes between tumors from pre- and post-menopausal patients with breast cancer was also analyzed based on the combination of status of three receptors. Together, the results suggest that mRNA expression of ESR1, ESR2, and PGR might differ depending on menopausal status in breast tumors with certain receptor status. More importantly, the change in the expression of ESR1 and ESR2 following menopause is in the opposite directions in breast cancer patients showing the need to identify particular molecular mechanisms regulating the expression of ER isoforms post-menopause in different directions in breast cancer patients, considering the high clinical importance of these receptors in terms of the prognosis of patients with breast cancer.

Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study

BackgroundMenopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.MethodsData from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.ResultsMHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).ConclusionsOur study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

Volume of hepatoid component and intratumor M2 macrophages predict prognosis in patients with hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS), a subtype of gastric cancer (GC), includes multiple tumor components, such as enteroblastic and tubular adenocarcinoma components. However, which component mostly contributes to the aggressive behavior of HAS remains unclear. Moreover, the role of tumor-associated macrophages (TAMs) has not been explored in HAS. This study evaluated the clinical significance of the proportion of the hepatoid component within the tumor, CD163 + macrophages, and macrophage colony-stimulating factor-1 (CSF-1) in HAS. In total, 56 cases of primary HAS were analyzed. In each case, hepatoid (HC), enteroblastic (EC), and tubular (TC) components were identified, and the ratio of HC to the entire tumor (hepatoid component ratio, HCR) was assessed to examine the correlation between HCR and clinicopathological features. Immunohistochemical staining for CD163 and CSF-1 was performed, and differences in immunohistochemical results among the three tumor components were analyzed. In each tumor component, the prognostic impact of CD163 and CSF-1 was examined. A high HCR was associated with worse overall survival (OS). CD163 + TAMs and CSF-1 immunoreactivity score in HC were significantly higher than those in the other components. High infiltration of CD163 + TAMs and a high CSF-1 immunoreactivity score in HC were associated with an aggressive course and worse OS. Multivariate analysis revealed the proportion of HC in HAS as an independent prognostic factor (HR = 3.176, p = 0.006). The HCR and CD163 + TAMs may be useful prognostic predictors, and TAMs may be novel therapeutic targets of HAS.

Multimodal Co-Attention Fusion Network With Online Data Augmentation for Cancer Subtype Classification.

It is an essential task to accurately diagnose cancer subtypes in computational pathology for personalized cancer treatment. Recent studies have indicated that the combination of multimodal data, such as whole slide images (WSIs) and multi-omics data, could achieve more accurate diagnosis. However, robust cancer diagnosis remains challenging due to the heterogeneity among multimodal data, as well as the performance degradation caused by insufficient multimodal patient data. In this work, we propose a novel multimodal co-attention fusion network (MCFN) with online data augmentation (ODA) for cancer subtype classification. Specifically, a multimodal mutual-guided co-attention (MMC) module is proposed to effectively perform dense multimodal interactions. It enables multimodal data to mutually guide and calibrate each other during the integration process to alleviate inter- and intra-modal heterogeneities. Subsequently, a self-normalizing network (SNN)-Mixer is developed to allow information communication among different omics data and alleviate the high-dimensional small-sample size problem in multi-omics data. Most importantly, to compensate for insufficient multimodal samples for model training, we propose an ODA module in MCFN. The ODA module leverages the multimodal knowledge to guide the data augmentations of WSIs and maximize the data diversity during model training. Extensive experiments are conducted on the public TCGA dataset. The experimental results demonstrate that the proposed MCFN outperforms all the compared algorithms, suggesting its effectiveness.

Evaluation of Cyclin D1 protein and its association with the clinicopathological characteristics and prognosis of lung cancer: A retrospective study from Southern Kerala, India.

Cyclin D1 is a protein that can enhance the proliferation of cancer cells and has been detected in various malignancies, including lung cancer. However, routine examinations for Cyclin D1 in lung cancer cases have not been conducted in Kerala. This study sought to evaluate the links between cyclin D1 expression, clinicopathological characteristics, and 2-year survival rates in lung cancer. This retrospective cohort study used medical records and paraffin blocks of lung cancer patients at the Regional Cancer Centre in Kerala, India, between 2015 and 2018. The data were collected from 61 subjects, comprising of lung adenocarcinoma (18%), lung squamous cell carcinoma (27.9%), non-small-cell lung carcinoma (18%), poorly differentiated carcinoma (19.7%), and negative for malignant cells (16.4%). Data analysis was conducted using SPSS. The study revealed that 31.10% of the lung cancer patients exhibited overexpression of cyclin D1. A significant correlation was observed between cyclin D1 expression and histopathological results (P = 0.002), indicating that the level of cyclin D1 might be linked to specific histopathological subtypes of lung cancer. Despite this significant finding, cyclin D1 expression did not show any association with the clinical stage of the cancer or other clinical characteristics of the patients. Furthermore, when examining the 2-year survival rates of the patients, the study found no significant difference between those who had overexpression of cyclin D1 and those who did not (P = 0.145). Cyclin D1 expression was associated with histology type of lung cancer with no significant association to prognosis.

A fully next-generation sequencing-based method of classifying molecular subtypes of endometrial cancer retains prognostic value and highlights racial disparities in disease-specific survival

A fully next-generation sequencing-based method of classifying molecular subtypes of endometrial cancer retains prognostic value and highlights racial disparities in disease-specific survival

Molecular subtypes of endometrioid endometrial cancer predict rates of lymph node and ovarian metastasis at the time of surgical staging

Molecular subtypes of endometrioid endometrial cancer predict rates of lymph node and ovarian metastasis at the time of surgical staging

MLLT3 knockdown suppresses proliferation and cell mobility in human lung adenocarcinoma.

Lung cancer is emerging as one of the most frequently encountered malignancies around the world that carries high morbidity and mortality. Lung adenocarcinoma (LUAD) has become the most common subtype of lung cancer. MLLT3 or named AF9 was first characterized in acute myeloid leukemia and can downregulate the expression of several critical genes. The aim of this study was to explore the function of MLLT3 in the progression of LUAD and related molecular mechanisms. Immunohistochemistry was employed to assess MLLT3 expression in LUAD tissues, while quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were utilized to detect MLLT3 expression levels in lung adenocarcinoma cell lines. These results revealed a significant overexpression of MLLT3 in LUAD cell lines and tissues. We further uncovered an association between MLLT3 expression profiles in LUAD tissues and metastasis, as well as TNM stage. Survival analysis showed that elevated MLLT3 correlated with a poorer survival rate. We also found that MLLT3 knockdown repressed LUAD cells invasion, migration, and proliferation in vitro, while inducing cell cycle arrest and apoptosis of LUAD cells. Moreover, knocking down MLLT3 inhibited tumor growth in vivo. Specific markers of apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and MLLT3-induced signaling were examined by Western blot. We demonstrated that MLLT3 knockdown inhibited the activity of the EGFR-MAPK/ERK signaling pathway, and MLLT3 might be a novel diagnostic biomarker and therapeutic target in lung adenocarcinomas.

Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance.

Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor tissues obtained from Korean patients with young breast cancer (YBC) aged ≤40 years. By integrating genomic, transcriptomic, and proteomic data, we identified five distinct functional subgroups that accurately represented the clinical characteristics and biological behaviors of patients with YBC. Our integrated approach could be used to determine the proteogenomic status of HER2, enhancing its clinical significance and prognostic value. Furthermore, we present a proteome-based homologous recombination deficiency (HRD) analysis that has the potential to overcome the limitations of conventional genomic HRD tests, facilitating the identification of new patient groups requiring targeted HR deficiency treatments. Additionally, we demonstrated that protein-RNA correlations can be used to predict the late recurrence of hormone receptor-positive breast cancer. Within each molecular subtype of breast cancer, we identified functionally significant protein groups whose differential abundance was closely correlated with the clinical progression of breast cancer. Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes.

Clinical Significance of FAM83G in Breast Cancer: Association With Triple-negative Subtype and Prognosis.

Family with sequence similarity 83 member G (FAM83G) plays an important role in cancer aggressiveness and patients' prognosis across various types of cancer. However, the association of FAM83G protein expression in breast cancer with clinicopathologic factors, breast cancer subtypes, and prognosis is not well characterized. This study aimed to elucidate the clinical significance of FAM83G protein expression in breast cancer. Immunohistochemistry was employed to examine FAM83G protein expression in 75 breast cancer tissues, assessing its potential as a biomarker for breast cancer patients. The Kaplan-Meier plotter was used to estimate the correlation between FAM83G mRNA expression and survival outcomes in TNBC patients. FAM83G protein was predominantly localized in the cytoplasm of breast cancer cells, exhibiting uniform expression throughout tumor tissues. FAM83G expression was significantly higher in cancerous areas compared to non-cancerous areas. High FAM83G expression was more prevalent in triple-negative breast cancer (TNBC) cases than in hormone receptor-positive cases. Although high FAM83G protein expression did not significantly impact prognosis in our cohort, a large-scale database analysis revealed an association between high FAM83G expression and poor prognosis in TNBC cases. This study demonstrates an association between high FAM83G expression in breast cancer tissues and TNBC. FAM83G may serve as a promising biomarker and therapeutic target for breast cancer patients.

The Diagnostic And Prognostic Role Of Immunohistochemistry In Head &amp; Neck Tumours Along With Radiological &amp; Histopathological Study

Background: Head &amp; neck tumors are defined as benign, premalignant &amp; malignant tumors above the clavicles, except the tumors of brain, spinal cord and esophagus. This includes tumors of paranasal sinus, nasal cavity, salivary glands, thyroid and upper aerodigestive tract, lymph nodes of neck, skin &amp; its appendages, soft tissue tumors, midline carcinomas &amp; metastatic tumors. Ultrasonography, computed tomography, magnetic resonance imaging were the modalities for initial evaluation. Histopathology was the GOLD standard for diagnosis followed by IHC for confirmation because correct diagnosis &amp; cancer subtyping of the neoplasia is essential for successful therapy and prognosis. Materials &amp; Methods: Study was conducted for 2 years with 100 specimens of head &amp; neck tumors. Thorough Radiological investigation was done followed by Histopathological examination including biopsy &amp; whole resected specimens. IHC markers appropriate to the histopathological diagnosis was done. Results: Among 100 patients of head &amp; neck tumors, most belonged to 5th decade with male: female ratio of 2.3:1. Squamous cell carcinoma (66%) followed by Lymphoma(11%), tumors of salivary glands(8%), metastatic lymphadenopathy(7%) were the lesions present. SCC was most common carcinoma in oral cavity, larynx, nasopharynx and ear with positive p63 marker. 1 case of Basal cell carcinoma with positive BerEP4 &amp; in NHL, salivary gland tumors &amp; Metastatic lymphadenopathy panel of IHC were included for confirmation. Conclusion: Immunohistochemistry has a diagnostic &amp; prognostic role in Head &amp; Neck tumors along with Radiological &amp; histopathological examination.

Comparison of the Predictive and Prognostic Capacities of Neutrophil, Lymphocyte and Platelet Counts and Tumor-infiltrating Lymphocytes in Triple-negative Breast Cancer: Preliminary Results of the PERCEPTION Study.

Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype, posing numerous challenges in clinical decision-making. Biomarkers are essential to personalize management of TNBC patients. While tumor infiltrating lymphocytes (TILs) are validated prognostic biomarkers, the requirement for tumor biopsy limits their routine use. Therefore, more accessible and reliable quantitative biomarkers are needed. Given the significant role of systemic inflammatory response in tumor onset and progression, assessing inflammatory cells via liquid biopsies emerges as a promising alternative. The PERCEPTION study, conducted at Centre Jean Perrin in France, aims to determine the correlation between TILs and peripheral blood components at diagnosis. An interim analysis was conducted after enrolling 50% of the estimated population, to evaluate study feasibility and preliminary correlations between blood cell counts and TILs. Sixty-one patients were enrolled over 4.5 years, demonstrating a good inclusion rate with minimal missing data. Preliminary results for 36 analyzable patients showed no correlation between the neutrophil-to-lymphocyte ratio (NLR) and TILs (rs=-0.19, 95%CI=-0.49-0.16, p=0.3). However, a moderate, positive, statistically significant correlation was found between NLR and the CD8/FoxP3 TILs ratio (rs=0.36, 95%CI=0.03-0.64, p=0.043). The probabilistic index of 0.7 (p=0.06) between NLR-high and NLR-low groups for this ratio supports the correlation. The interim analysis of the PERCEPTION study confirms the feasibility of correlating blood cell counts with TILs in TNBC. Although no significant correlation was observed between NLR and TILs, the moderate positive correlation between the CD8/FoxP3 ratio and TILs suggests a potential link between systemic inflammation and local immune response. These findings underscore the potential of blood-based markers as non-invasive surrogates for TILs, encouraging further research to enhance prognosis and guide treatment strategies in TNBC.