Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses.Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that our model effectively predicted the response of patients to immune-based treatments.Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Sentinel lymph node metastasis after neoadjuvant treatment in breast cancer:Any size matters?

One of the advantages of neoadjuvant chemotherapy(NAC) treatments is its ability to convert patients who need a mastectomy in breast conservative surgery. NAC has also increased the conversion of node positive patients into node negative in around 40% allowing the use of sentinel node biopsy(SLN) in this setting. Timing of SLN biopsy after NAC has been a subject of debate. In patients with clinically node negative before NAC,rates of success and false negative rates of SLN after NAC are similar to those in the adjuvant setting,so SLN after NAC in previous negative axilla has been incorporated in the staging of the axilla. More controversial is its use in patients with positive axillary nodes before NAC who convert to node negative after NAC. Several randomized studies have reported the identification rates and the false negative rates of the SLN after NAC,concordant in the importance of surgical technique. As there is an agreement in the abandon of the immunohistochemistry(IHC) for SLN in the adjuvant setting as SLN IHC detected metastasis appear to have no impact on overall survival,in patients with SLN after NAC the inclusion of isolated tumor cell(ITC) as positive nodes lowers the false negative rates of the technique,suggesting the importance of assessing the SLN by IHC after NAC and considering it as residual disease. Longer follow up is needed to determine the prognostic implications of ITC in the SLN after NAC.

Mutation-based circulating tumor DNA detection approach to monitoring the therapy response in breast cancer

Breast cancer is responsible for the highest number of cancer-related mortalities in females.1 For breast cancer patients who need systematic chemotherapy,especially with locally-advanced breast cancer,neoadjuvant chemotherapy(NAC)is pivotal in optimizing subsequent treatment strategies and is essential for enhancing overall survival rates.2 Thus,monitoring NAC response is crucial to identify the patients achieving a pathologic complete response(pCR)and the non-responders early to de-escalate or change therapy,respectively.However,current monitoring methods,such as imaging technologies(e.g.,ultrasound and magnetic resonance imaging[MRI]),traditional serum biomarkers(e.g.,CA15-3 and CEA),and core-needle biopsy with Ki67 assay during the NAC,cannot meet the need to measure the dynamic response in NAC accurately.

Application of Survival Quilts for prognosis prediction of gastrectomy patients based on the Surveillance,Epidemiology,and End Results database and China National Cancer Center Gastric Cancer database

Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.

DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy

Background:Pathological complete response(pCR)of axillary lymph nodes(ALNs)is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy(NAC),and ALN status is an important prognostic factor for breast cancer patients.This study aims to develop a new predictive clinical model to assess the ALN pCR rate after NAC.Methods:This was a retrospective series of 467 patients who had biopsy-proven positive ALNs at diagnosis and underwent ALN dissection from 2007 to 2014 at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences.We analyzed the clinicopathologic features of the patients and developed a nomogram to predict the probability of ALN pCR.A multivariable logistic regression stepwise model was used to construct a nomogram to predict ALN pCR in node-positive patients.The adjusted area under the receiver operating characteristic curve(AUC)was calculated to quantify the ability to rank patients by risk.Internal validation was performed using the 50/50 hold-out validation method.The nomogram was externally validated with prospective cohorts of 167 patients from 2016 to 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences and 114 patients from 2018 to 2020 at Beijing Tiantan Hospital.Results:In this retrospective study,115(24.6%)patients achieved ALN pCR after NAC.Multivariate analysis showed that clinical tumor stage(Odds ratio[OR]:0.321,95%confidence interval[CI]:0.121-0.856;P=0.023);primary tumor response(OR:0.189;95%CI:0.123-0.292;P<0.001),and estrogen receptor status(OR:0.530,95%CI:0.304-0.925;P=0.025)were independent predictors of ALN pCR.The nomogram was constructed based on the result of multivariate analysis.In the internal validation of performance of nomogram,the AUCs for the training and test sets were 0.719 and 0.753,respectively.The nomogram was validated in external cohorts with AUCs of 0.720,which demonstrated good discriminatory power in these data sets.Conclusion:We developed a nomogram to predict the likelihood of axillary pCR in node-positive breast cancer patients after NAC.The predictive model performed well in multicenter prospective external validation.This practical tool could provide information to surgeons regarding whether to perform additional ALN dissection after NAC.Trial registration:ChiCTR.org.cn,ChiCTR1800014968.

Resistance of breast cancer cells to paclitaxel is associated with low expressions of miRNA-186 and miRNA-7

Aim:Neo-adjuvant chemotherapy is a common approach for the complex treatment of breast cancer(BC)and paclitaxel(PTX)is frequently included in the therapeutic regimen.However,the effect of PTX-based treatment is hard to predict precisely based on routinely used markers.As microRNAs are considered a new promising class of biomarkers,the link between miRNA expression and PTX resistance of BC cells needs to be well investigated.This study aimed at the identification of miRNAs associated with responses of BC cells to PTX.Methods:Intrinsic PTX sensitivity and miRNA profiling were assayed in five BC cell lines to identify candidate miRNAs.Selected miRNA(n.15)expressions were analyzed by real-time-quantitative polymerase chain reaction(RT-qPCR)in BC tissue samples(n.31)obtained from a diagnostic biopsy.Results were analyzed in the context of the effect of two cycles of PTX and the effect of the completed scheme of neoadjuvant therapy.The study’s design facilitated the evaluation of the effect of PTX on cells and the identification of features of the microRNA expression profiles associated exclusively with sensitivity to this drug.Results:miR-186 and miR-7 expression in BC tissues was higher in patients with better outcomes of PTX-based neoadjuvant therapy.Conclusion:High expressions of miR-186 and miR-7 are associated with good response to PTX,whereas their low expressions may be associated with resistance to PTX in BC,indicating the possibility of developing innovative test systems for the prediction of the PTX response,which can be used before the start of neo-adjuvant chemotherapy for BC.

Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients

Background: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. Methods: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). Results: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. Conclusions: A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin

Background Proteins containing the Jumonji C(JmjC)domain participated in tumorigenesis and cancer progression.However,the mechanisms underlying this effect are still poorly understood.Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2(JARID2)—a JmjC family protein—in breast cancer,as well as its latent association with obesity.Methods Immunohistochemistry,The Cancer Genome Atlas,Gene Expression Omnibus,and other databases were used to analyze the expression of JARID2 in breast cancer cells.Growth curve,5-ethynyl-2-deoxyuridine(EdU),colony formation,and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion.Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness.RNA-sequencing,Kyoto Encyclopedia of Genes and Genomes,and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates.Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2.The results were further verified using co-immunoprecipitation and glutathione S-transferase(GST)pull-down experiments.Using chromatin immunoprecipitation(ChIP)sequencing,we sought the target genes that JARID2 and metastasis-associated protein 1(MTA1)jointly regulated;the results were validated by ChIP-PCR,quantitative ChIP(qChIP)and ChIP-reChIP assays.A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes.Results In this study,we found that JARID2 was highly expressed in multiple types of cancer including breast cancer.JARID2 promoted glycolysis,lipid metabolism,proliferation,invasion,and stemness of breast cancer cells.Furthermore,JARID2 physically interacted with the nucleosome remodeling and deacetylase(NuRD)complex,transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated(BRCA2),RB transcriptional corepressor 1(RB1),and inositol polyphosphate-4-phosphatase type II B(INPP4B).Additionally,JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in the breast cancer microenvironment.Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer.Conclusion Our data indicated that JARID2 promoted breast tumorigenesis and development,confirming JARID2 as a target for cancer treatment.

Genomic mutation signatures in primary breast cancer and their axillary metastatic lymph nodes

Breast cancer is one of the most common malignant tumors in women all over the world.Metastasis represents a major adverse progression of breast cancer,resulting in poor survival duration.Axillary lymph node metastasis is often the first step of systemic metastasis process of breast cancer.However,themechanismof lymph node metastasis and the genomic signatures of primary breast tumors and lymph node metastasis are still under exploration.Whole exome sequencing was applied to primary breast cancer,axillary metastatic lymph nodes,andwhite blood cells from10Chinesewomen patients in our study.Single nucleotide variants(SNVs)and copynumber variants(CNVs)were compared between primary tumors and lymph nodes for individual patients.There are somatic SNVs(average 5.58±2.56 per megabase)in primary breast cancers and somatic SNVs(average 5.46±2.66 per megabase)in axillary metastatic lymph nodes were identified,which is corresponding to a semblable mutation burden in two malignant sites(P=0.81).No difference was found in CNVs(P=0.33).In primary breast cancer,somatic SNVs(48.12±13.80%)and CNVs(61.72±35.00%)were overlapping with somatic SNVs(49.43±12.30%)and CNVs(72.01±24.31%)in axillary metastatic lymph nodes.Nine genes were screened for significant specificmutations in primary tumors,and 15 genes were significantly mutated in metastatic lymph nodes.Using MutSigCV screening,it was found that HRNR and AHNAK2 are lymph node metastasis-specific genes.In our study,primary breast tumors are directly related to axillary lymph node metastases together and there are most SNVs and CNVs which were overlapping in primary andmetastatic sites.These variants which are overlapping is closely related to themetastatic process of tumor invasion with early genetic variability.This is the first timeto prove the concept of polyclonalmetastaticmodel and in thismodelmore than one clonemigrates establish the metastases to axillary lymph nodes.This study was approved by the institutional review board(IRB)of the Cancer Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College,China(approval No.NCC2016G-030)on March 3,2016.

Efficacy of volume navigation in assessment of extent of breast cancer

Objective Volume navigation (Vnav) combines real-time ultrasound (US) with previously acquired volume data from magnetic resonance imaging (MRI) data into a single display. The efficacy of Vnav for preoperative assessment of the extent of breast cancer lesions was evaluated in the present study.Methods Twenty-nine breast cancer patients were evaluated using Vnav during second-look US or preoperative mapping. Retrospective chart review was performed. Correlation detection rates and pathological results were evaluated.Results Vnav identified lesions that were initially detected on MRI in 23 of 29 patients (79.3%). Of the 23 patients who had US correlated lesions, pathological diagnoses of the corresponding lesions were as follows: benign (n=9) and malignant (n=14).Conclusion Vnav may be a useful technique for identification of the extent of breast cancer lesions.

Long-term outcomes of intraoperative radiotherapy for early-stage breast cancer in China: amulticenter real-world study

Dear Editor,Intraoperative radiotherapy(IORT)is an accelerated par-tial breast irradiation(APBI)treatment that is accom-plished intraoperatively.Numerous clinical trials indicate that IORT is safe and effective,non-inferior to standard whole-breast external beam radiotherapy(EBRT)for low-risk patients who receive breast-conserving surgery[1-3].Nevertheless,these studies mainly included non-Asians and thus lack adequate evidence to support the value of IORT in Asian patients with breast cancer.

Genetic variations in triple-negative breast cancers undergoing neo-adjuvant chemotherapy

Aim:Triple negative breast cancer(TNBC)is known as aggressive subtype and have no identified targeted therapies.We examined the relationship of neoadjuvant chemotherapy response to genetic variations of TNBC.Methods:The tumors used in this study were collected from Showa University Hospital,Japan.Thirteen formalin-fixed paraffin-embedded tumors from Japanese TNBC patients who underwent neoadjuvant chemotherapy were used for analysis.Of these,eight surgically resected tumors showed progressive disease and/or recurrence after treatment(PD/REC),and biopsy tissues from five patients showing pathological complete response(pCR)were analyzed.DNA extracted from tissue sample were analyzed.The Miseq system and Trusight Tumor Sequence panel kit were used to sequence 174 amplicons over 82 exons of 26 cancer-related genes to identify genetic mutations.Results:Seven somatic non-synonymous variants were detected in three genes(FOXL2,PIK3CA,and TP53)in all five pCR patients,and six somatic non-synonymous variants in two genes(PTEN and TP53)were detected in six of eight PD/REC patients.Eight of 13 TNBC tumors were found to have TP53 pathogenic variants,in both pCR and PD/REC cases.Conclusion:Although TP53 variation was detected in both pCR and PD/REC cases,each location and type of the variant were different.We could not identify genetic mutations associated with chemotherapy response and recurrence.

CACA Guidelines for Holistic Integrative Management of Breast Cancer

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway

Background:Mild traumatic brain injury(mTBI)is a common neurological trauma that can lead to cognitive impairment.The sirtuin-1(SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)pathway has been reported to have neuroprotective effects in rats with craniocerebral injury.We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI,focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods:We included forty 6-week-old male Sprague-Dawley rats in this study.Rats were randomly divided into four groups:controlled cortical impactor(CCI,n=10),sham operation(sham,n=10),electroacupuncture-treated CCI(CCI+EA,n=10),and electroacupuncture-treated sham(sham+EA,n=10)group.Randomization was performed by assigning a random number to each rat and using a random number table.The mTBI rat model was established using a controllable cortical impactor.Electroacupuncture therapy was performed on the back of rats,by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment.We evaluated spatial learning and memory functions with the Morris water maze test.We performed quantitative real-time polymerase chain reaction(qRT-PCR),western blotting,adenosine triphosphate(ATP)determination,and mitochondrial respiratory chain complex I(MRCC I)determination on rat hippocampal tissue.We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays,and compared differences between groups using bilateral Student’s t-tests.Results:Compared with the sham group,SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group(P<0.01).Although this expression was upregulated following electroacupuncture,it did not reach the levels observed in the sham group(P<0.05).Compared with the sham group,MRCC I and ATP levels in the CCI group were significantly reduced,and increased after electroacupuncture(P<0.01).In the Morris water maze,electroacupuncture reduced the incubation period of rats and increased average speed and number of crossing platforms(P<0.05).Conclusion:Electroacupuncture may improve cognitive function in the mTBI rat model by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

Revealing the roles of TLR7, a nucleic acid sensor for COVID-19 in pan-cancer

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus’’s nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We found TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with Mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

Paget's disease of the nipple in males:two case reports and literature review

Male breast cancer acounts for less than 0.5%of all breast cancer,and Paget's disease of the breast in males is extremely rare.Here,we report 2 cases of Paget's disease of the nipple areola complex with invasive ductal carcinoma as typical examples of male PDB.Case 1 was a 64-year old man with an altered appearance of the left nipple,itching and redness,without a palpable breast mass at first.Case 2 was a 55-year-old man with a palpable mass in the left breast and histologically confirmed Paget'sdisease of the nipple with invasive ductal carcinoma.Both patients underwent modified radical mastectomy but with different adjuvant therapies and remained well during follow-up with no recurrence.Furthermore,we reviewed all the sporadic cases of male PDB from the literature.This may help contribute to the development of diagnostic strategies and appropriate interventions for male Paget's disease of the breast.