Background:Existing neoadjuvant therapies for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer have not achieved optimal clinical outcomes, thus prompting the investigation of novel treatment strategies. Given the emerging significance of HDAC inhibitors in the management of advanced breast cancer, this study investigated the efficacy and safety of chidamide plus chemotherapy as neoadjuvant therapy for patients with HR+/HER2- breast cancer. Methods:This single arm, open-label, multicentre, phase 2 trial was conducted at three hospitals in China. Patients aged 18-75 years who had treatment-naïve, stage II-III HR+/HER2- breast cancer with an Eastern Cooperative Oncology Group performance status of 0-1 were enrolled. Patients received oral chidamide at a dose of 20 mg on days 1, 4, 8, and 11 of each 21-day cycle. The chemotherapy regimen consisted of four cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) administered every three weeks, followed by four cycles of docetaxel (100 mg/m2) administered every three weeks. The primary endpoint was the rate of residual cancer burden (RCB) 0-I. This study is registered with ClinicalTrials.gov, NCT05400993. Findings:Between May 23, 2022 and July 6, 2023, a total of 54 female patients (median age: 50 years [range, 26-75]) were recruited. The RCB 0-I rate was 35.2% (19 of 54, 95% confidence interval [CI], 22.7%-49.4%). The most frequent grade 3 or 4 adverse events were decreased neutrophil count (70%) and decreased white blood cell (67%). No treatment-related deaths occurred. Interpretation:The combination of chidamide and chemotherapy shows the potential to be an alternative neoadjuvant therapy option for patients with HR+/HER2- breast cancer. Funding:Shenyang Municipal Science and Technology Program (Grant No. 22-321-32-18), Shenzhen Chipscreen Biosciences Co., Ltd.

Antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) are widely used for HER2-positive metastatic breast cancer, but their efficacy in the neoadjuvant setting remains under investigation. The MUKDEN 06 trial (NCT05426486), a multicentre, randomised, phase 2b study, compared ARX788 (anti-HER2 ADC) plus pyrotinib (TKI) with the standard neoadjuvant regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCbHP) in female patients with early or locally advanced HER2-positive breast cancer. The primary endpoint was the pathological complete response (pCR, ypT0/is, ypN0) rate, analyzed in the intention-to-treat population. pCR was achieved in 70.6% (48/68) of patients receiving ARX788 plus pyrotinib, compared to 51.5% (35/68) in the TCbHP group, with a significant absolute difference of 19.1% (95% CI, 2.7-34.6; p = 0.023). No treatment-related deaths occurred. The most common grade 3-4 adverse events were diarrhea and hepatic dysfunction in the ARX788 plus pyrotinib group, and fatigue, nausea and anorexia in the TCbHP group. Interstitial lung disease (ILD)/pneumonitis and ocular events were observed with ARX788 plus pyrotinib, indicating a distinct safety profile. These findings offer clinical insights into the potential of dual HER2-targeted blockade with an ADC and TKI as an optional neoadjuvant strategy for patients with early or locally advanced HER2-positive breast cancer.

Innovative therapeutic strategies are urgently needed to address the ongoing global health concern of hepatobiliary pancreatic malignancies. This review summarizes the latest and most comprehensive research of chimeric antigen receptor (CAR-T) cell engineering immunotherapy for treating hepatobiliary pancreatic cancers. Commencing with an exploration of the distinct anatomical location and the immunosuppressive, hypoxic tumor microenvironment (TME), this review critically assesses the limitations of current CAR-T therapy in hepatobiliary pancreatic cancers and proposes corresponding solutions. Various studies aim at enhancing CAR-T cell efficacy in these cancers through improving T cell persistence, enhancing antigen specificity and reducing tumor heterogeneity, also modulating the immunosuppressive and hypoxic TME. Additionally, the review examines the application of emerging nanoparticles and biotechnologies utilized in CAR-T therapy for these cancers. The results suggest that constructing optimized CAR-T cells to overcome physical barrier, manipulating the TME to relieve immunosuppression and hypoxia, designing CAR-T combination therapies, and selecting the most suitable delivery strategies, all together could collectively enhance the safety of CAR-T engineering and advance the effectiveness of adaptive cell therapy for hepatobiliary pancreatic cancers.

Cancer represents a significant global health threat, with the World Health Organization reporting millions of new cases annually. Dysregulation in cellular homestasis leads to the aggressive and heterogeneous nature of cancers. Conventional treatments encounter challenges due to the inhomogeneity of tumor microenvironment (TME). Ubiquitination and deubiquitination, as typical post-transcriptional modifications (PTMs), play crucial roles in various cellular processes, with deubiquitinating enzymes (DUBs) influencing cancer progression. Over 100 DUB species, particularly the major ubiquitin-specific proteases (USPs) family, impact cancer through diverse mechanisms. Non-coding RNAs (ncRNAs), notably miRNAs, lncRNAs, and circRNAs, add to the complexity of cancer. Recently, the interplay between USPs and ncRNAs has been demonstrated to affect key cancer traits, including proliferation, apoptosis, metastasis, angiogenesis, and stem cell characteristics. The connection between USPs and ncRNAs also extends to control metabolic reprogramming and immune modulation within the TME, comprehensively shaping cancer behaviors. Targeting the USP-ncRNA axis presents a promising avenue for therapeutic intervention, offering potential in overcoming treatment resistance. By further leveraging nanotechnological advancements in precise delivery, this review highlights the translational potential of USP-ncRNA interactions for cancer therapy.

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

BackgroundThe CXCL12-CXCR4/CXCR7 axis is garnering growing attention. But the comprehension of its function in the progression of HCC remains controversial. The purpose of this study was to investigate the effects of CXCL12 and its receptor on the prognosis of patients with viral hepatitis-associated HCC after hepatectomy.MethodsA total of 86 patients had been enrolled who had undergone hepatectomy for HCC and followed up to July 31, 2019, and their clinicopathological and follow-up data were recorded. Tumor and peritumoral tissues were obtained to detect the expression of CXCL12, CXCR4, and CXCR7 using immunohistochemistry. Real-time polymerase chain reaction was utilized to detect hepatitis B or C virus loads, while survival analysis was performed using the Kaplan–Meier method. Furthermore, the Cox proportional hazards regression model was employed to analyze the factors affecting the prognosis.ResultsThe results revealed that the CXCL12, CXCR4, and CXCR7 expression in tumor tissues was lower than in the corresponding non-tumor tissues in 20.93%, 22.09%, and 23.26% of the patients, respectively, and that only CXCL12 was found to be related to the extrahepatic invasion of HCC. The survival analysis and Cox regression showed that only CXCL12 was associated with the postoperative survival of patients with HCC, and that it was an independent prognostic risk factor in the CXCL12-CXCR4/CXCR7 axis. The CXCL12low group represented shorter progression-free survival and lower overall survival rates. However, the subgroup analysis displayed that the survival difference associated with CXCL12 was only manifested in patients with higher expression of CXCR4 or CXCR7 in HCC, as compared to the surrounding tissues.ConclusionsOur findings suggest that, when assessing the prognostic significance of CXCL12 in HCC, it is essential to consider the expression level of its receptor. Nevertheless, CXCL12 can potentially serve as a promising prognostic marker for HCC.

Abstract Triple‐positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan‐human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin‐dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II–III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%–84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0–I was 75% (95% CI, 46.8%–91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%–98.5%). Mean Ki‐67 level was significantly reduced from 45.0% (95% CI, 19.5%–70.5%) at baseline to 17.2% (95% CI, 0.7%–33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment‐related deaths occurred. This four‐drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

VEGFR-2 kinase inhibitors are clinically approved drugs that can effectively target cancer angiogenesis. However, such inhibitors have adverse effects such as skin toxicity, gastrointestinal reactions and hepatic impairment. In this study, machine learning and Topomer CoMFA, which is an alignment-dependent, descriptor-based method, were employed to build structural activity relationship models of potentially new VEGFR-2 inhibitors. The prediction ac-curacy of the training and test sets of the 2D-SAR model were 82.4 and 80.1%, respectively, with KNN. Topomer CoMFA approach was then used for 3D-QSAR modeling of VEGFR-2 inhibitors. The coefficient of q2 for cross-validation of the model 1 was greater than 0.5, suggesting that a stable drug activity-prediction model was obtained. Molecular docking was further performed to simulate the interactions between the five most promising compounds and VEGFR-2 target protein and the Total Scores were all greater than 6, indicating that they had a strong hydrogen bond interactions were present. This study successfully used machine learning to obtain five potentially novel VEGFR-2 inhibitors to increase our arsenal of drugs to combat cancer.

Protein ubiquitination, one of the most significant post-translational modifications, plays an important role in controlling the proteins activity in diverse cellular processes. The reversible process of protein ubiquitination, known as deubiquitination, has emerged as a critical mechanism for maintaining cellular homeostasis. The deubiquitinases (DUBs), which participate in deubiquitination process are increasingly recognized as potential candidates for drug discovery. Among these DUBs, ubiquitin-specific protease 9× (USP9X), a highly conserved member of the USP family, exhibits versatile functions in various cellular processes, including the regulation of cell cycle, protein endocytosis, apoptosis, cell polarity, immunological microenvironment, and stem cell characteristics. The dysregulation and abnormal activities of USP9X are influenced by intricate cellular signaling pathway crosstalk and upstream non-coding RNAs. The complex expression patterns and controversial clinical significance of USP9X in cancers suggest its potential as a prognostic biomarker. Furthermore, USP9X inhibitors has shown promising antitumor activity and holds the potential to overcome therapeutic resistance in preclinical models. However, a comprehensive summary of the role and molecular functions of USP9X in cancer progression is currently lacking. In this review, we provide a comprehensive delineation of USP9X participation in numerous critical cellular processes, complicated signaling pathways within the tumor microenvironment, and its potential translational applications to combat therapeutic resistance. By systematically summarizing the updated molecular mechanisms of USP9X in cancer biology, this review aims to contribute to the advancement of cancer therapeutics and provide essential insights for specialists and clinicians in the development of improved cancer treatment strategies.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is characterized by invasive growth, rapid metastasis and chemoresistance. Trastuzumab is an effective treatment for HER2+ breast cancer; however, trastuzumab resistance leads to cancer relapse and metastasis. CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) has been considered as a new immune checkpoint for tumor-induced immunosuppression. The role of CMTM6 in trastuzumab resistance remains unknown. Here, we uncover a role of CMTM6 in trastuzumab-resistant HER2+ breast cancer. CMTM6 expression was upregulated in trastuzumab-resistant HER2+ breast cancer cell. Patients with high CMTM6 expressing HER2+ breast cancer had worse overall and progression-free survival than those with low CMTM6 expression. In vitro, CMTM6 knockdown inhibited the proliferation and migration of HER2+ breast cancer cells, and promoted their apoptosis, while CMTM6 overexpression reversed these effects. CMTM6 and HER2 proteins were co-localized on the surface of breast cancer cells, and CMTM6 silencing reduced HER2 protein levels in breast cancer cells. Co-immunoprecipitation revealed that CMTM6 directly interacted with HER2 in HER2+ breast cancer cells, and CMTM6 overexpression inhibited HER2 ubiquitination. Collectively, these findings highlight that CMTM6 stabilizes HER2 protein, contributing to trastuzumab resistance and implicate CMTM6 as a potential prognostic marker and therapeutic target for overcoming trastuzumab resistance in HER2+ breast cancer.

Tumors have evolved in various mechanisms to evade the immune system, hindering the antitumor immune response and facilitating tumor progression. Immunotherapy has become a potential treatment strategy specific to different cancer types by utilizing multifarious molecular mechanisms to enhance the immune response against tumors. Among these mechanisms, the ubiquitin-proteasome system (UPS) is a significant non-lysosomal pathway specific to protein degradation, regulated by deubiquitinating enzymes (DUBs) that counterbalance ubiquitin signaling. Ubiquitin-specific proteases (USPs), the largest DUB family with the strongest variety, play critical roles in modulating immune cell function, regulating immune response, and participating in antigen processing and presentation during tumor progression. According to recent studies, the expressions of some USP family members in tumor cells are involved in tumor immune escape and immune microenvironment. This review explores the potential of targeting USPs as a new approach for cancer immunotherapy, highlighting recent basic and preclinical studies investigating the applications of USP inhibitors. By providing insights into the structure and function of USPs in cancer immunity, this review aims at assisting in developing new therapeutic approaches for enhancing the immunotherapy efficacy.

e12603 Background: Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib plus dalpiciclib (cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with triple-positive breast cancer (TPBC), but the efficacy still needs improvement. This pilot study explored the efficacy and safety of adding trastuzumab to this neoadjuvant regimen in TPBC. Methods: Patients received five 28-day cycles of pyrotinib (320 mg once daily), dalpiciclib (125 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), followed by surgery. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, residual cancer burden (RCB), change in Ki-67 level from baseline to surgery, and safety. Results: Between February 16, 2022 and June 2, 2022, 12 patients were enrolled. Seven (58%; 95% CI, 27.7-84.8) patients achieved tpCR and bpCR. The rate of RCB 0-I was 75% (95% CI, 46.8-91.1%). ORR was 92% (95% CI, 64.6-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5% - 70.5%) at baseline to 17.2% (95% CI, 0.7% - 33.7%) after neoadjuvant therapy (P<0.05). The most common grade 3 adverse events were diarrhea (4 [33%]) and decreased neutrophil count (3 [25%]). No grade 4 events or treatment-related deaths occurred. Conclusions: This four-drug neoadjuvant regimen shows promising pathological response in patients with TPBC, with an acceptable safety profile. The results warranted further validation. Clinical trial information: NCT05228951 .

Background: Emerging data have supported the immunostimulatory role of radiotherapy, which could exert a synergistic effect with immune checkpoint inhibitors (ICIs). With proven effective but suboptimal effect of ICI and chemotherapy in triple-negative breast cancer (TNBC), we designed a pilot study to explore the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) plus adebrelimab and chemotherapy in TNBC patients. Methods: Treatment-naïve TNBC patients received two cycles of intravenous adebrelimab (20 mg/kg, every 3 weeks), and SBRT (24 Gy/3 f, every other day) started at the second cycle, then followed by six cycles of adebrelimab plus nab-paclitaxel (125 mg/m² on days 1 and 8) and carboplatin (area under the curve 6 mg/mL per min on day 1) every 3 weeks. The surgery was performed within 3–5 weeks after the end of neoadjuvant therapy. Primary endpoint was pathological complete response (pCR, ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), residual cancer burden (RCB) 0-I, and safety. Results: 13 patients were enrolled and received at least one dose of therapy. 10 (76.9%) patients completed SBRT and were included in efficacy analysis. 90% (9/10) of patients achieved pCR, both RCB 0-I and ORR reached 100% with three patients achieved complete remission. Adverse events (AEs) of all-grade and grade 3–4 occurred in 92.3% and 53.8%, respectively. One (7.7%) patient had treatment-related serious AEs. No radiation-related dermatitis or death occurred. Conclusions: Adding SBRT to adebrelimab and neoadjuvant chemotherapy led to a substantial proportion of pCR with acceptable toxicities, supporting further exploration of this combination in TNBC patients. Funding: None. Clinical trial number: NCT05132790.

CMTM6 has been connected to the development of several malignancies. However, it is still unknown what function CMTM6 serves in pancreatic adenocarcinoma (PAAD). We obtained RNA sequencing information of PAAD from public datasets and predicted statistical significance of CMTM6 survival in accordance with Kaplan-Meier curves. Gene set enrichment assessment (GSEA) was employed to analyze changes in pathways. Then, we systematically investigated the association involving CMTM6 and the immunological traits within the tumor microenvironment (TME) of PAAD, including immune pathways, immunomodulators, immune infiltrating cells, inflammatory activities, and immunotherapy response prediction. To demonstrate the biologically malignant properties of CMTM6 expression, the Cell Counting Kit-8, transwell experiments, colony formation, and wound healing were utilized. Upregulated CMTM6 expression was revealed within PAAD tissues, which was associated with more frequent somatic mutations and worse survival outcomes. Specifically, CMTM6 expression represented stronger immune infiltration, inflammatory activity, and better immunotherapeutic response in TME. Functional studies revealed that CMTM6 promoted the ability to proliferate, migrate, and invade. Additionally, CMTM6 and PD-L1 had a positive relationship, and CMTM6 can co-immunocoprecipitate with PD-L1 protein in pancreatic cell lines. CMTM6 overexpression shapes the inflammatory TME with a strong immune response. These findings support that CMTM6 is an immunotherapeutic target with promising effect to treat PAAD.

526 Background: The 21-gene (Oncotype Dx), PAM50 (Prosigna) and Chinese-based 28-gene (RecurIndex) are validated genomic assays that provide prognostic information for distant recurrence risk in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). In this study, we aim to compare the differences in prediction performance by different multigene assays and gene expression profiles between the Eastern and the Western. Methods: Under the Affymetrix U133 platforms, the differences in gene expressions and risk scores from the Eastern population comprised of GSE20685 (n = 327) and part of GSE45255 (n = 95), and the Western population GSE25066 (n = 508) and the European in GSE45255(n = 44) were analyzed respectively. Patients were stratified by 21-gene Recurrence Scores (RS) of low (0-10), intermediate (11-25) and high (26-100) and categorized by ROR-S score of PAM50 of low (0-40), intermediate (41-60) and high (61-100). For 28-gene, a recurrence index for distant recurrence (RI-DR) cutoff of 33 was used to classify patients into high- and low-risk groups. Wilcoxon rank test was used to test for continuous variables and the chi-square test was used for categorical variables. Results: The Western population has significantly higher RS (85.9 vs. 65.5, p < 0.001) and ROR-S (57.4 vs.53.7, p = 0.034) scores than the Eastern population. The distribution of 28-gene risk groups was significantly different between races with a higher proportion of high-risk in the Western (10.5% vs. 6.6%, p = 0.035). The low-risk patients in the Eastern stratified by 28-gene assay had significantly higher distant metastasis-free survival (DMFS) rates than high-risk (80% vs. 52%, p < 0.001), which compared with Oncotype Dx RS (96% vs. 76%, p < 0.001) and PAM50 ROR-S (93% vs. 72%, p < 0.001). At the same time, the analysis of gene expressions revealed significantly high expressions of YWHAB, SF3B5, CKAP5, and DDX39A in the Eastern than that in the Western. However, most genes from 21-gene and ROR-S were more highly expressed in the Western than that in the Eastern. Conclusions: 21-gene and PAM50 provide the good performance and show similar patterns in the prognosis of EBC; However, the DMFS rate of the high-risk in the Eastern population determined by 28-gene was much lower than 21-gene and PAM50, which means there are bigger chemo-benefit in the high-risk from 28-gene. In conclusion, 28-gene has better performance in the prognosis of the Eastern population and is a more suitable tool for Eastern breast cancer patients.

Background Colon cancer is the foremost reason of cancer-related mortality worldwide. Colon adenocarcinoma constitutes 90% of colon cancer, and most patients with colon adenocarcinoma (COAD) are identified until advanced stage. With the emergence of an increasing number of novel pathogenic mechanisms and treatments, the role of mitochondria in the development of cancer, has been studied and reported with increasing frequency. Methods We systematically analyzed the effect of mitochondria-related genes in COAD utilizing RNA sequencing dataset from The Cancer Genome Atlas database and 1613 mitochondrial function-related genes from MitoMiner database. Our approach consisted of differentially expressed gene, gene set enrichment analysis, gene ontology terminology, Kyoto Encyclopedia of Genes and Genomes, independent prognostic analysis, univariate and multivariate analysis, Kaplan–Meier survival analysis, immune microenvironment correlation analysis, and Cox regression analysis. Results Consequently, 8 genes were identified to construct 8 mitochondrial-related gene model by applying Cox regression analysis, CDC25C, KCNJ11, NOL3, P4HA1, QSOX2, Trap1, DNAJC28, and ATCAY. Meanwhile, we assessed the connection between this model and clinical parameters or immune microenvironment. Risk score was an independent predictor for COAD patients’ survival with an AUC of 0.687, 0.752 and 0.762 at 1-, 3- and 5-year in nomogram, respectively. The group with the highest risk score had the lowest survival rate and the worst clinical stages. Additionally, its predictive capacity was validated in GSE39582 cohort. Conclusion In summary, we established a prognostic pattern of mitochondrial-related genes, which can predict overall survival in COAD, which may enable a more optimized approach for the clinical treatment and scientific study of COAD. This gene signature model has the potential to improve prognosis and treatment for COAD patients in the future, and to be widely implemented in clinical settings. The utilization of this mitochondrial-related gene signature model may be benefit in the treatments and medical decision-making of COAD.

目的 探讨第8版非小细胞肺癌TNM分期Ⅲa期患者的预后.方法 纳入2001年至2010年间于本溪市中心医院手术且术后未接受任何辅助治疗的Ⅲa期非小细胞肺癌患者215例,将患者分为pT2aN2M0、pT2bN2M0、pT3N1M0和pT4N1M0共4个亚组,分析并比较患者的预后.结果 4个亚组间生存率有统计学差异(P<0.05),且pT2aN2M0和pT3N1M0亚组、pT2bN2M0和pT3N1M0亚组、pT3N1M0和pT4N1M0亚组比较,5年生存率也有统计学差异(均P<0.05).鳞状细胞癌和腺癌患者比较,5年生存率无统计学差异;中分化患者的5年生存率明显高于高分化患者(P<0.05);存在脉管浸润和胸膜浸润患者的5年生存率明显低于无脉管浸润和胸膜浸润的患者(均P<0.05).结论 非小细胞肺癌Ⅲa期各亚组间患者的生存预后有显著差异,建议对当前Ⅲa期亚组进行更细致的分期,以更准确地预测患者预后.

Objective: Studying the prognosis of breast cancer (BRCA) is of great significance for clinical treatment. LncRNA has been shown to be significantly important in breast cancer, but only few studies exist that relate to the prognosis of lncRNA. This study aimed to build a lncRNA-based breast cancer prognosis risk model using the data from TCGA datasets. Methods: we used the TCGA public database to explore the differential expression of lncRNA and cancer prognosis in breast cancer patients. The RNA-Seq data and clinical data pertaining to 1090 BRCA patients in the TCGA database were downloaded and analyzed. The prognosis-related lncRNAs in BRCA patients were identified in the training set and validated in the test set and the complete data set. ROC was performed to determine the optimal cut-off point for patient risk classification, and survival analysis was performed to determine its significance in prognosis prediction. Results: A total of 19 prognosis-associated differentially expressed lncRNAs (LSINCT5, TRG-AS1, CH17-189H20.1, RP11-1399P15.1, RP11-344P13.6, RP5-1028K7.2, AL022344.7, USP30-AS1, RP11-522120.3, AL122127.25, BHLHE40-AS1, CHRM3-AS2, LINC00704, RP5-107303.2, RP11-316M21.6, CTA-384D8.31, RP11-10J5.1, RP11-426L16.3, RB11-344B5.2) were screened out. The BRCA prognosis risk assessment model based on 19-lncRNA can predict the survival rate of breast cancer patients. Conclusion: This model can predict the prognosis of breast cancer patients and these 19 lncRNAs can be used as potential molecular markers for breast cancer prognosis prediction.