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The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Here, the expression of LSM1 mRNA in breast cancer was estimated using The Cancer Genome Atlas (TCGA), Oncomine, TIMER and bc-GenExMiner databases. We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in breast cancer (BRCA) patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer.

Background ALKBH1 is an important enzyme involved in various cellular processes that regulates RNA demethylation in humans. While its contribution to tumor progression is known, its role in gastric cancer remains unclear. Further research is needed to explore the potential of ALKBH1 in clinicopathology, tumor immune microenvironment, and precision oncology for STAD. Methods This study used a multi-omics approach to identify ALKBH1 as an independent diagnostic biomarker for STAD with a correlation to advanced clinical status and poor overall survival rate. We analyzed publicly available datasets from GEO and TCGA, identifying differentially expressed genes in STAD and examined their relationship with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. We also explored ALKBH1 gene expression in different regions of the STAD using spatial transcriptomics. In addition, we utilized spatial transcriptomic and single-cell RNA-sequencing methods to investigate the correlation between PGAM1 and immune cells. We further confirmed our results by analyzing 60 STAD patient samples and examining the relationship between ALKBH1 expression, clinicopathological features, and prognosis using immunohistochemistry and bioinformatics. Results Our study revealed the expression of key gene regulators in gastric cancer that were associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators were positively linked to distinct immune cells in six immune datasets and played a vital role in immune cell infiltration in STAD. We found that high ALKBH1 expression was associated with macrophage infiltration in STAD. Moreover, pharmacogenomic analysis of renal cancer cell lines indicated that ALKBH1 inactivation was correlated with increased sensitivity to specific small-molecule drugs. Conclusion To sum up, the study indicates that alterations in ALKBH1 may play a role in STAD advancement and reveal new diagnostic and prognostic implications of ALKBH1 in STAD. It emphasizes the importance of ALKBH1 in the tumor immune microenvironment, implying its potential utility as a precision medicine tool and for drug screening in STAD.

The human ATP binding cassette (ABC) family of transporter proteins plays an important role in the maintenance of homeostasis

Acquired resistance to aromatase inhibitors (AIs) is a significant clinical issue in endocrine therapy for estrogen receptor (ER) positive breast cancer which accounts for the majority of breast cancer. Despite estrogen production being suppressed, ERα signaling remains active and plays a key role in most AI-resistant breast tumors. Here, we found that amphiregulin (AREG), an ERα transcriptional target and epidermal growth factor receptor (EGFR) ligand, is crucial for maintaining ERα expression and signaling in acquired AI-resistant breast cancer cells. AREG was deregulated and critical for cell viability in ER+ AI-resistant breast cancer cells, and ectopic expression of AREG in hormone responsive breast cancer cells promoted endocrine resistance. RNA-sequencing and reverse phase protein array analyses revealed that AREG maintains ERα expression and signaling by activation of PI3K/Akt/mTOR signaling and upregulation of Forkhead Box M1 (FoxM1) and Serum- and glucocorticoid-inducible kinase 3 (SGK3) expression. Our study uncovers a previously unappreciated role of AREG in maintaining ERα expression and signaling, and establishes the AREG-ERα crosstalk as a driver of acquired AI resistance in breast cancer.

Background: Vacuum-assisted breast biopsy (VABB) for benign breast tumor excision is a developing trend in breast surgery. The most common complication of VABB is hematoma. We assessed the efficiency of the thrombin-gelatin matrix (TGM) for hemostasis after VABB. Methods: From December 2013 to June 2017, 147 patients with breast tumors > 2 cm in size were treated with a 7-gauge ultrasound-guided EnCor EnSpire® breast biopsy system. After VABB, the TGM was applied using an iron-tube device. After injection, brief external compression for 15 min and postoperative bandage compression for approximately 12 h were applied. The medical records were reviewed and analyzed for hematoma and acute bleeding at 1 and 3 months after VABB. Results: A total of 72 patients received hemostasis via TGM, and 75 patients received hemostasis by compression. The rates of postoperative acute bleeding in the TGM group were significantly lower than those in the non-TGM group (5.5% vs. 22.7%, p = 0.003). Among patients with hematoma, there was no statistically significant difference between the two groups (25% vs. 26.7%, p = 0.85). Conclusions: This is the first cohort study to apply the TGM hemostatic matrix for post-VABB hemostasis. The TGM hemostatic matrix could be an option for patients with large breast tumors.

Simple Summary Breast cancer emergencies have become a rapidly evolving field in medicine during the last ten years. Carcinogenesis is a multiparametric process that involves diverse factors such as genetic, environmental, or aging. Recent research that elucidates the tumor biology and molecular pathways that mediate cancer progression and drug resistance has led to the development of various molecular targeted therapies involving monoclonal antibodies, small molecule receptor tyrosine kinase inhibitors, and agents that block downstream signaling pathways in breast cancer. Abstract Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies.

e13011 Background: The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Methods: In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of LSM1 in patients with breast cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of LSM1 proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichmente. Finally, we explored the mechanisms underlying LSM1 involvement in BRCA by using gene set enrichment analysis. Results: We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in BRCA patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib, and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer. Conclusions: In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for breast cancer.

e12590 Background: Patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC) who achieve a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) have favorable prognoses. Multiple pretreatment systemic inflammatory markers (SIMs), based on peripheral blood cell counts, have been reported as predictors of pCR in BC patients. The markers include neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, and systemic inflammation response index (SIRI= neutrophil × monocyte / lymphocyte count), etc. However, the most significant SIM remains controversial among studies and the variations among different molecular subtypes remain unknown. Methods: We retrospectively reviewed 233 patients with stage I–III HER2-positive BC who received NST and subsequently underwent surgery in Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Data on multiple pretreatment SIMs were collected. The most significant SIM were analyzed for predictive significance with other clinicopathologic factors by using stepwise logistic regression with forward selection. The data was conducted to illustrate a nomogram plot for determining pCR probability. Results: Among the pretreatment SIMs, only SIRI was significantly related to pCR by optimal cut-off value of 1.7 ×109/L. Stepwise logistic analyses indicated that the clinical T and N stage, HER2 immunohistochemistry (IHC) score, PR expression, and targeted therapy regimen were independent predictors of pCR, with an area under the curve (AUC) of 0.74. Sub-analysis was performed after stratifying into T stage subgroups (T1-2 vs. T3-4). Significant predictors In the T1-2 subgroup were clinical N stage, HER2 IHC score, PR, and targeted therapy regimen (AUC=0.722). Significant predictors in the T3-4 subgroup were SIRI and ER (AUC=0.824). The Hosmer–Lemeshow test revealed the predictive ability was a good fit to actual observation. A T-stage-stratified nomogram based on the logistic model was built. Conclusions: In HER2 positive BC patients receiving NST, low pretreatment SIRI is predictive of pCR in T3-4 subgroup. Our nomogram served as an efficient tool to predict pCR and to assist clinical decision support before neoadjuvant treatment.

e13012 Background: The human ATP binding cassette (ABC) family of transporter proteins plays an important role in the maintenance of homeostasis in vivo. The aim of this study is to evaluate the potential diagnostic, prognostic, and therapeutic value of the ABCA10 gene in BRCA. Methods: In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of BRCA from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive in silico therapeutics screening to identify agents with subclass-specific efficacy. Results: We found that ABCA10 expression was downregulated in different subgroups of breast cancer and strongly correlated with pathological stage in BRCA patients. Low expression of ABCA10 was associated with BRCA patients showing shorter overall survival (OS). ABCA10 expression may be regulated by promoter methylation, copy number variation (CNV) and kinase, and is associated with immune infiltration. Our study also demonstrated the potential role of ABCA10 modifications in tumor microenvironment (TME) cellular infiltration. Nevertheless, the regulatory mechanism remains unknown and immunotherapy is marginal in BRCA. We demonstrate the expression of different ABCA10 modulators in breast cancer associated with genetic variants, deletions, tumor mutation burden (TMB) and TME. Mutations in ABCA10 are positively associated with different immune cells in six different immune databases. Mutations in ABCA10 and immune cell infiltration play an important role in breast cancer. Conclusions: Overall, this study provides evidence that ABCA10 could become the potential targets for precision treatment and new biomarkers in the prognosis of breast cancer.

Utilization of circulating tumor DNA as a novel and noninvasive test for diagnosis confirmation, therapy selection, and cancer surveillance is a rapidly growing area of interest. In the wake of FDA approval of a liquid biopsy test, it is important for clinicians to acknowledge the obvious clinical utility of liquid biopsy for cancer management throughout the course of the disease. This case report describes a female with invasive ductal adenocarcinoma of the breast, where liquid biopsy was instrumental for her cancer characterization and personalized therapy selection.

A 59-year-old woman presented to our hospital after 2 days f progressive abdominal pain, nausea and vomiting. The physial examination showed a distended abdomen, hypoactive bowel ounds, and diffuse abdominal tenderness. The laboratory tests evealed white-cell count of 6450 per cubic millimetre with 78% eutrophils. A contrast enhanced computed tomographic scan of he abdomen revealed lipomatosis of small bowel and causing owel obstruction (Fig. 1). An explorative laparotomy discovered ipomatosis of small intestine andmesentery (Fig. 2A), which were ausing intestinal obstruction. Segmental resection of tumournvolved intestine was performed. The pathological diagnosis was onfirmed with lipomatous polyposis of ileum. Under microscopy ections, the specimen showed small intestinal tissuewithmultiple ubmucosal lipomatous nodules and composed of abnormal collecions of mature adipose tissue (Panel 2B). The patient started oral ntakewithwater at postoperative day 7 and regular diet at postoprative day 9. Postoperative wound infection was presented. After ound change dressing, the patient was discharged in good health month later. Primary small intestinal tumoursareuncommon,whichaccount or about 1% of all gastrointestinal tumours, and primary lipomas f the small intestine are rare [1]. Most patients are presentedwith aroxysmal abdominal pain, haemorrhage of digestive tract, and bdominal masses. Surgical intervention should be considered if ausing intestinal obstruction secondary to intussusception.

A 28 year-old woman presented to our hospital after several pisodes of bloody vomitus for 1 day. The physical examinaions showed pale conjuctiva and a palpable mass over left upper uadrant of abdomen without tenderness. The laboratory tests evealed white-cell count of 11,980/Cumm with 80% neutrophils nd haemoglobin of 6.6 g/dL. An upper gastrointestinal panenoscopy showed isolated gastric varices and external compression f stomach from posterior wall of body (Fig. 1). A contrast enhanced omputed tomographic scan of the abdomen revealed a huge cystic ass, 18 cm × 11 cm × 12 cm, over the pancreatic tail and budding he splenic hilum. The splenic vein was anteriorly displaced and ompressed (Fig. 2A, arrow). Distal pancreatectomy and splenecomy were performed (Fig. 2B). The pathological diagnosis was onfirmed with mucinous cystadenoma of pancreas. The patient ecovered well and discharged in good health 5 days after the opertion. She received an upper gastrointestinal panendoscopy 1 year ater for regular follow-up and no gastric varices were presented. Left-sided portal hypertension (LSPH) is a rare clinical syndrome hich may lead to bleeding from isolated gastric varices [1]. Panreatic disease is the most common aetiology. LSPH is also one of he rare curable syndromes causing portal hypertension. Since haeatemesis is a life-threatening condition, as early to diagnose and reat as possible may result in better prognosis.