Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

Low-dose aspirin can inhibit exosomal release induced by radiotherapy in breast cancer and attenuate its inhibitory effect on NK cell proliferation.

BACKGROUND: Breast cancer (BC) seriously threatens women's health. Aspirin plays a key role in the treatment and prognosis of BC. OBJECTIVE: To explore the effect of low-dose aspirin on BC radiotherapy through the mechanism of exosomes and natural killer (NK) cells. METHODS: BC cells were injected into the left chest wall to establish a BC model in nude mice. Tumor morphology and size were observed. Immunohistochemical staining for Ki-67 was used to observe the proliferation of tumor cells. TUNEL was used to detect the apoptosis of cancer cells. Protein levels of exosomal biogenesis- and secretion-related genes (Rab 11, Rab27a, Rab27b, CD63, and Alix) were detected by Western blot. Flow cytometry was used to detect apoptosis. Transwell assays were used to detect cell migration. A clonogenic assay was used to detect cell proliferation. Exosomes of BT549 and 4T1-Luc cells were extracted and observed by electron microscopy. After the coculture of exosomes and NK cells, the activity of NK cells was detected by CCK-8. RESULTS: The protein expression of genes related to exosomal genesis and secretion (Rab 11, Rab27a, Rab27b, CD63, and Alix) in BT549 and 4T1-Luc cells was upregulated under radiotherapy treatment. Low doses of aspirin inhibited exosome release from BT549 and 4T1-Luc cells and alleviated the inhibitory effect of BC cell exosomes on NK cell proliferation. In addition, knocking down Rab27a reduced the protein levels of exosome-related and secretion-related genes in BC cells, further enhancing the promotive effect of aspirin on NK cell proliferation, while overexpressing Rab27a had the opposite effect. Aspirin was combined at a radiotherapeutic dose of 10 Gy to enhance the radiotherapy sensitivity of radiotherapy-tolerant BC cells (BT549R and 4T1-LucR). Animal experiments have also verified that aspirin can promote the killing effect of radiotherapy on cancer cells and significantly inhibit tumor growth. CONCLUSION: Low doses of aspirin can inhibit the release of BC exosomes induced by radiotherapy and weaken their inhibition of NK cell proliferation, promoting radiotherapy resistance.

Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer.

Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer globally, and its treatment remains a significant challenge. Therefore, it is crucial to comprehend the microenvironment to improve therapy and prognosis urgently. In this study, we utilized bioinformatic methods to analyze the transcription expression profile of patient samples with complete clinical information from the TCGA-LUAD datasets. To validate our findings, we also analyzed the Gene Expression Omnibus (GEO) datasets. The super-enhancer (SE) was visualized using the peaks of the H3K27ac and H3K4me1 ChIP-seq signal, which were identified by the Integrative Genomics Viewer (IGV). To further investigate the role of Centromere protein O (CENPO) in LUAD, we conducted various assays including Western blot, qRT-PCR, flow cytometry, wound healing and transwell assays to assess the cell functions of CENPO in vitro. The overexpression of CENPO is linked to a poor prognosis in patients with LUAD. Strong signal peaks of H3K27ac and H3K4me1 were also observed near the predicted SE regions of CENPO. CENPO was found to be positively associated with the expression levels of immune checkpoints and drug IC50 value (Roscovitine and TGX221), but negatively associated with the fraction levels of several immature cells and drug IC50 value (CCT018159, GSK1904529A, Lenaildomide, and PD-173074). Additionally, CENPO-associated prognostic signature (CPS) was identified as an independent risk factor. The high-risk group for LUAD is identified based on CPS enrichment, which involved not only endocytosis that transfers mitochondria to promote cell survival in response to chemotherapy but also cell cycle promotion that leads to drug resistance. The removal of CENPO significantly suppressed metastasis and induced arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients.

Pan-cancer landscape of CENPO and its underlying mechanism in LUAD.

BACKGROUND: Centromere protein O (CENPO) is a newly discovered constitutive centromeric protein, associated with cell death. However, little is known about how CENPO expression is associated with human cancers or immune infiltration. Here, we assessed the function of CENPO in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro and in vivo experiments. METHODS: Sangerbox and TCGA databases were used to evaluate the CENPO expression level in different human cancer types. A subsequent evaluation of the potential role of CENPO as a diagnostic and prognostic biomarker in pancancer was conducted. The CENPO mutations were analyzed using the cBioPortal database and its function was analyzed using the LinkedOmics and CancerSEA databases. The TIMER2 and TISIDB websites were used to find out how CENPO affects immune infiltration. The expression level of CENPO in LUAD was revealed by TCGA database and immunohistochemical (IHC) staining. Targetscan, miRWalk, miRDB, miRabel, LncBase databases, and Cytoscape tool were used to identify microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that regulate expression and construct ceRNA network. Subsequently, loss-of-function assays were performed to identify the functions of CENPO on the malignant behavior and tumor growth of LUAD in vitro and in vivo experiments. RESULTS: In most cancers, CENPO was upregulated and mutated, which predicted a poorer prognosis. Furthermore, infiltration of CENPO and myeloid-derived suppressor cells (MDSC) showed a significant positive correlation, while T-cell NK infiltration showed a significant negative correlation in most cancers. CENPO was expressed at high levels in LUAD and was correlated with p-TNM stage. Furthermore, CENPO knockdown suppressed the malignant phenotypes of LUAD cells, manifested by slower proliferation, cycle in G2, increased apoptosis, decreased migration, and attenuated tumorigenesis. Furthermore, CENPO knockdown decreased CDK1/6, PIK3CA, and inhibited mTOR phosphorylation, suggesting that the mTOR signaling pathway may be involved in CENPO-mediated regulation of LUAD development. CONCLUSIONS: In pan-cancer, especially LUAD, CENPO may be a potential biomarker and oncogene. Furthermore, CENPO has been implicated in immune cell infiltration in pan-cancer and represents a potential immunotherapeutic target for tumor therapy.

Resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, and bilateral partial external iliac arteries with artificial vessel replacement during radical endometrial cancer surgery: a case report.

BACKGROUND: Endometrial carcinoma (EC) is a common malignant tumor of the female reproductive system, often accompanied by lymph node metastasis. Artificial vascular implantation is a common surgical treatment for mediastinal tumors and abdominal aortic aneurysms but is rarely used in gynecological surgery. CASE PRESENTATION: A 54-year-old female patient was first admitted to the hospital in January 2018 due to "irregular vaginal bleeding over 3 months". CT showed a mass in the uterine cavity, and several swollen lymph nodes in the retroperitoneum and pelvic cavity. The initial diagnosis was an endometrial malignant tumor. We performed radical endometrial cancer surgery with parallel resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, bilateral external iliac arteries, and artificial vessel replacement, which was successful, with good postoperative recovery and no lesion progression at 3 years postoperative follow-up. CONCLUSION: This is an early case of gynecological clinical use of prostheses. Through multidisciplinary cooperation, the surgical resection rate of patients with EC in radical surgery was improved without serious fatal complications and achieved a high long-term postoperative survival rate.

Linc00996 is a favorable prognostic factor in LUAD: Results from bioinformatics analysis and experimental validation.

Background: Linc00996 has been reported in a variety of malignant tumors, but its potential role and significance in lung adenocarcinoma (LUAD) are not fully understood. The authors investigated the expression and biological behavior of Linc00996 in LUAD and elucidated the function of its potential target genes. Materials and methods: The data of Linc00996 expression in cancers were derived from GEPIA. GEO and TCGA datasets were used to identify the differential expression of Linc00996 in LUAD and analyze the respective correlation between different expression levels and LUAD stage and survival prognosis. We further elucidated the potential biological processes and pathways involved with Linc00996 in LAUD by GSEA. ssGSEA was applied to explore the relationship between Linc00996 and immune activity. Finally, the clinical impact of Linc00996 was assessed in 61 patients with LUAD, and the biological functions of Linc00996 were determined by a series of experiments in vitro, such as CCK8, colony formation, migration, and invasion assays. Results: Compared with adjacent normal lung tissues, Linc00996 was significantly downregulated in LUAD, and its expression was negatively correlated with T stage, N stage, and pathological stage. An in vitro study suggested that enhanced Linc00996 expression could inhibit cell proliferation, clonal formation, migration, and invasion in LUAD cell lines. Via GSEA and ssGSEA, we observed that Linc00996 might be connected with immune infiltration in LUAD, and Linc00996 might inhibit tumorigenesis and metastasis by regulating antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways. Conclusion: Linc00996 is a novel tumor suppressor in LUAD and may suppress the tumorigenesis and metastasis of LUAD via the tumor-related signaling pathway, such as antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.

MTA1 Expression Can Stratify the Risk of Patients with Multifocal Non-Small Cell Lung Cancers ≤3 cm.

PURPOSE: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤3 cm. METHODS: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data. RESULTS: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433-25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤3 cm. CONCLUSION: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤3 cm. Patients with MTA1 immunohistochemical score >5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.

CBX7, a Potential Prognostic Biomarker in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a major type of NSCLC and has high morbidity and mortality. The identification of useful prognostic biomarkers for LUAD is important. CBX7 has been reported in various cancers yet its expression level and potential roles have not been fully understood. METHODS: GEPIA, Oncomine, TCGA, KM plotter and OSluca databases were used to explore the expression profile and prognostic effects of CBX7 mRNA expression in patients with LUAD. TIMER was used to explore the relationship between CBX7 and immune infiltrating cells. GSEA was used to further explore the potential biological process and pathways regulated by CBX7 in LUAD. Lastly, IHC detection of CBX7 in 95 samples was used to validate the result. RESULTS: We found CBX7 was downregulated in LUAD in GEPIA, Oncomine and TCGA databases. TCGA, KM plotter and OSluca databases suggested that CBX7 was associated with poor clinical outcomes and low survival rate. Using TIMER, we found that CBX7 might be associated with immune infiltration. Via gene set enrichment analysis, we found that tumor-associated biological processes and signaling pathways were enriched in the CBX7 downregulated group. Using clinical samples, we found that CBX7 protein has low expression in LUAD and was associated with poor survival. CONCLUSION: CBX7 might serve as a promising biomarker and potential molecular target in LUAD.

Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

OBJECTIVE: It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype. METHODS: Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses. RESULTS: Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20-2.21) and OS (HR 1.53, 95% CI 1.19-1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45-2.85) and OS (HR 2.26, 95% CI 1.46-3.52) were also poor in the subgroup of patients with the presence of an MP component. CONCLUSIONS: Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.

Epidemiology characteristics of ethnic minority colorectal cancer in Yunnan in Southwestern China.

BACKGROUND: Colorectal cancer (CRC) is one of the world's deadliest cancers, and its mortality rate has been on the rise in China. Yunnan is a region with a higher concentration of ethnic minorities. CRC affects many people from ethnic minority groups, which differ from Han in terms of their age and gender compositions. METHODS: We collected samples from 1,016 cases of CRC patients along with their case files at Yunnan Provincial Cancer Hospital from the period between January 2013 and December 2018. RESULTS: In total, 7.1% (n=72) of all lung cancer cases diagnosed from 2013 to 2018 in Yunnan Provincial Cancer Hospital occurred in patients 40 years old or younger, 44% (n=447) were 40 to 60 years old, and 48.9% (n=497) were 60 years old or above. The composition ratio of CRC patients in the different age groups differed significantly and enhanced significantly with age, with a statistical significance of P<0.05. A total of 33.6% (n=38) of 113 minority patients and 16.8% (n=152) of 903 Han patients reported a history of smoking, and 23.0% (n=26) of 113 minority patients and 14.6% (n=132) of Han patients had a history of drinking. Long-term smoking and drinking are significantly associated with the incidence of CRC, and this was more significant among ethnic minorities (P<0.05). CONCLUSIONS: The high incidence of CRC in Yunnan is strongly related to patients' lifestyles, and diet should be a core focus of efforts to prevent and treat CRC. Early screening and regular check for common tumor markers can also help to reduce the incidence of CRC and provide a basis for improvements in CRC treatment and prognosis in Yunnan.

MicroRNA expression profiling of lung adenocarcinoma in Xuanwei, China: A preliminary study.

MicroRNAs (miRNAs) have been proved to be related to the development and progression of lung cancer. However, the expression signatures of miRNAs in lung adenocarcinoma in Xuanwei are not yet clear. The current study aimed to identify the potential miRNA profiles in lung adenocarcinoma in Xuanwei by microarray.The miRNA profiles in 24 lung adenocarcinoma and paired non-tumor tissues in Xuanwei were ascertained by using the Exiqon miRCURY LNA microRNA Array (v.18.0). The results of the microarrays were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) detection. Bioinformatics analysis was used to carry out the functional annotations of differentially expressed miRNAs.One hundred fifty five differentially expressed (≥2-fold change) miRNAs were identified (65 upregulated and 90 downregulated). QRT-PCR was used to validate the top 4 most upregulated and downregulated miRNAs, and the results were generally consisted with microarray. Furthermore, the differentially expressed miRNAs were significantly enriched in numerous common pathways that were bound up with cancer. The pathways included focal adhesion and signaling pathways, such as cyclic guanosine monophosphate -protein kinase G (cGMP-PKG) signaling pathways, mitogen-activated protein kinase (MAPK) signaling pathway, and Hippo signaling pathway, etc.Our study identified the potential miRNA profiles in lung adenocarcinoma in Xuanwei by microarray. These miRNAs might be used as biomarkers for diagnosis and/or prognosis for lung cancer in Xuanwei and therefore warrant further investigation. Further study is needed to reveal the potential role of these miRNAs in the carcinogenesis of XuanWei Lung Cancer (XWLC).

Application of serum microRNA-9-5p, 21-5p, and 223-3p combined with tumor markers in the diagnosis of non-small-cell lung cancer in Yunnan in southwestern China.

PURPOSE: Xuanwei City is located in late Permian coal-accumulating areas of the northeastern region of Yunnan Province. In China, morbidity and mortality from lung cancer are highest in Yunnan. Identifying useful circulating markers suitable for the diagnosis of lung cancer in this region is quite meaningful. In this study, we evaluated diagnostic roles of serum miR-9-5p, 21-5p, 223-3p, 135b-5p, 339-5p, and 501-5p in patients with non-small-cell lung cancer (NSCLC) in Yunnan. Moreover, we evaluated the diagnostic performance of several tumor markers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), and squamous cell carcinoma-related antigen (SCC). METHODS: Quantitative real-time polymerase chain reaction detected six miRNAs in the serum of 104 NSCLC patients and 50 cancer-free controls. Other markers, including CEA, CYFRA21-1, and SCC, in serum were also measured. The diagnostic ability of miRNAs and tumor markers was evaluated by receiver operating characteristic (ROC) curve analysis. The diagnostic performance of these serum markers was also evaluated in Xuanwei and non-Xuanwei subjects, because the etiological and the epidemiological characteristics of lung cancer in Xuanwei were quite different from those in other regions. RESULTS: Serum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were upregulated in NSCLC patients, compared with cancer-free controls. No significant difference was found in miR-135b-5p, miR-339-5p, and miR-501-5p expression. The area under ROC curves (AUCs) of miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were 0.706, 0.765, 0.744, 0.749, 0.735, and 0.616, respectively. When combined, miRNAs and tumor markers yielded the highest diagnostic power, with AUC of 0.886, sensitivity of 82.69%, and specificity of 88.00%. In Xuanwei subjects, miR-223-3p and CEA may be suitable biomarkers to distinguish NSCLC from cancer-free states with AUCs of 0.752 and 0.791, respectively. The diagnostic power of the combination of miRNAs and tumor markers was still the highest in both subgroups (region: Xuanwei and non-Xuanwei; stages: I-II and III-IV). CONCLUSION: Serum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC could be potential diagnostic biomarkers for NSCLC patients in Yunnan. miRNAs and tumor markers should be combined to diagnose NSCLC, as it showed better ability for screening patients with NSCLC.

The clinical use of circulating microRNAs as non-invasive diagnostic biomarkers for lung cancers.

Many studies have investigated the diagnostic role of circulating microRNAs (miRNAs) in patients with lung cancer; however, the results still remain inconclusive. An updated system review and meta-analysis was necessary to give a comprehensive evaluation of diagnostic role of circulating miRNAs in lung cancer. Eligible studies were searched in electronical databases. The sensitivity and specificity were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The between-study heterogeneity was evaluated by Q test and I2 statistics. Subgroup analyses and meta-regression were further performed to explore the potential sources of heterogeneity. A total of 134 studies from 65 articles (6,919 patients with lung cancer and 7,064 controls) were included for analysis. Overall analysis showed that circulating miRNAs had a good diagnostic performance in lung cancers, with a sensitivity of 0.83, a specificity of 0.84, and an AUC of 0.90. Subgroup analysis suggested that combined miRNAs and Caucasian populations may yield relatively higher diagnostic performance. In addition, we found serum might serve as an ideal material to detecting miRNA as good diagnostic performance. We also found the diagnostic role of miRNAs in early stage lung cancer was still relatively high (the sensitivity, specificity and an AUC of stage I/II was 0.81, 0.82 and 0.88; and for stage I, it was 0.80, 0.81, and 0.88). We also identified a panel of miRNAs such as miR-21-5p, miR-223-3p, miR-155-5p and miR-126-3p might serve as potential biomarkers for lung cancer. As a result, circulating miRNAs, particularly the combination of multiple miRNAs, may serve as promising biomarkers for the diagnosis of lung cancer.

The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis.

Published studies have investigated the prognostic role of cyclooxygenase-2 (COX-2) expression in patients with esophageal cancer (EC), but the result remains controversial. Thus, this meta-analysis was conducted to comprehensively evaluate the impact of COX-2 expression on the prognostic value in patients with EC. Relevant studies were identified from PubMed, EMBASE, and Web of Science databases. Studies that detected the COX-2 expression by immunohistochemistry and evaluated the relationship between COX-2 expression and overall survival (OS) or clinicopathological parameters were used in our analysis. The summary hazard ratios (HRs) or odds ratios were calculated to assess the risk or hazard association. A total of 25 studies, which included 2,465 patients, were included in our meta-analysis. Our analysis suggested that overexpression of COX-2 was associated with poor OS (HR =1.60, 95% CI =1.32-1.94, P<0.001). Subgroup analyses by race, percentage of high/positive COX-2 expression, histology type, treatment, and sample size all suggested significant association. Moreover, overexpression of COX-2 was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and TNM stage. This meta-analysis suggested that overexpression of COX-2 might serve as a prognostic biomarker for EC. Large well-designed prospective studies are needed to confirm our conclusion.

Impact of polysomy 17 on HER2 testing of invasive breast cancer patients.

BACKGROUND: Current American Society of Clinical Oncology/College of American Pathologists guidelines define HER2-positive tumors as those with >6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17) ratio>2.2. These guidelines are potentially contradictory in tumors with polysomy of chromosome 17. The current study was performed to determine the impact of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas. METHODS: Chromosome 17 copies and HER2 gene status were identified by fluorescent in situ hybridization in 384 cases with invasive breast cancer, and the corresponding HER2 expression was obtained by immunohistochemistry stain. RESULTS: The average CEP17 copy number for the group was 2.1 (range, 1.0-12.4). Forty-eight cases (13.8%, 48/348) were identified as chromosome 17 polysomy with CEP 17 copy number≥3. Ninety-two (26.4%) cases had >6 copies of HER2 per nucleus, and 92 cases (26.4%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (>2.2) guideline. Polysomy 17 showed poorly positive correlations with both HER2 gene copy number and HER2 overexpression (P<0.01, r=0.338 and 0.271, respectively). The distribution of clinicopathologic parameters of Polysomy 17 tumors was more similar to HER2 negative than HER2 positive tumors. CONCLUSIONS: Polysomy 17 is a crucial cause of equivocal HER2 testing results by FISH, depending on which criterion (ratio vs. absolute number) is used for interpretation. Polysomy 17 cannot be an independent predictive factor for HER2 gene amplification or protein overexpression.

[Expression of PEPT2 mRNA in lung tissue of rats with pulmonary fibrosis].

BACKGROUND AND OBJECTIVE: Pulmonary fibrosis is a common pathological phenomenon in lung cancer patients after chemotherapy or radiotherapy. It is also a key hindrance to the transport of drugs to lung tissue. Peptide transporters have become a target of the rational design of peptides and peptide drugs. The aim of this study is to investigates the expression of peptide transporter 2 (PEPT2) mRNA in the lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis. METHODS: Fifty healthy adult Sprague-Dawley rats were randomly divided into five groups. One group was untreated (control), the second group was injected with normal saline solution (NS), and the three remaining groups were treated with a single dose of bleomycin to induce pulmonary fibrosis (BLM). Rats from the NS group were killed by exsanguination on day 14. Rats from the BLM group were killed by exsanguination on days 7, 14, and 28. The lung samples were observed under light microscopy and the hydroxyproline concentration was determined. The expression levels of PEPT2 mRNA were measured by RT-PCR. RESULTS: The morphological study showed that collagenous fiber proliferated in the lungs of rats injected with BLM, indicating pulmonary fibrosis. This proliferation was apparent at 14 d post-injection and especially at 28 d post-injection. Hydroxyproline levels increased seven days post-injection compared with the control group and NS group, but there was no significant statistical difference (P>0.05). Hydroxyproline levels significantly increased (P<0.05) 14 d and 28 d post-infection. The change in the lung tissue pathology coincided with the change in hydroxyproline levels. There were no significant changes of pulmonary PEPT2 mRNA expression levels among the different groups (P>0.05). CONCLUSION: PEPT2 is a potential peptide drug target in the treatment of pulmonary fibrosis, although there were no significant changes of PEPT2 mRNA expression in the lungs of rats with bleomycin-induced pulmonary fibrosis.