IL-7R Expression Correlates with Prognosis in Breast Cancer.

BACKGROUND: The tumor microenvironment (TME) exerts a significant influence on the development, invasion, metastasis, and drug resistance of breast cancer. Therefore, this study sought to investigate potential prognostic factors and markers indicative of TME remodeling in breast cancer, utilizing data from the TCGA database. METHODS: In this study, transcriptome RNA-seq data from 1222 breast cancer samples were processed using CIBERSORT and ESTIMATE algorithms. We conducted a differential gene expression analysis utilizing COX regression analysis and constructed protein-protein interaction (PPI) networks for enhanced visualization. Through univariate COX analysis and cross-analysis within PPI networks, the Interleukin-7 receptor (IL-7R) emerged as a potential predictor. Subsequently, we performed a comprehensive investigation encompassing single-gene survival analysis, clinical correlation assessment, and GSEA enrichment analysis targeting IL-7R as a core gene associated with prognosis. We examined the expression of IL-7R in human breast cancer and normal breast tissue through clinical studies and cytology experiments, followed by an indepth analysis of the relationship between IL-7R and breast cancer. RESULTS: The survival analysis revealed that breast cancer patients with elevated IL-7R expression experienced prolonged survival compared to those with lower IL-7R levels. Results obtained from the Wilcoxon rank-sum test, along with clinical and cellular experiments, indicated higher IL-7R expression in tumor samples compared to normal samples. Correlation tests conducted between IL-7R expression and clinicopathological stage characteristics highlighted statistically significant associations between IL-7R expression and the T and M stages. Additionally, cell classification analysis of tumor-infiltrating immune cells (TIC) proportion showed that activated CD4+ T cells and CD8 T cells of memory B cells were positively correlated with IL-7R expression. These findings further underscored the impact of IL-7R levels on the tumor microenvironment (TME). CONCLUSION: IL-7R emerges as a potential prognostic indicator for breast cancer patients, particularly in sustaining the immunoactive status of the tumor microenvironment (TME) and contributing to immune reconstitution. These findings offer novel insights into breast cancer treatment strategies.

Surgery challenges and postoperative complications of lung cancer after neoadjuvant immunotherapy.

BACKGROUND: In China, real-world data on surgical challenges and postoperative complications after neoadjuvant immunotherapy of lung cancer are limited. METHODS: Patients were retrospectively enrolled from January 2018 to January 2023, and their clinical and pathological characters were subsequently analyzed. Surgical difficulty was categorized into a binary classification according to surgical duration: challenging or routine. Postoperative complications were graded using Clavien-Dindo grades. Logistic regression was used to identify risk factors affecting the duration of surgery and postoperative complications greater than Clavien-Dindo grade 2. RESULTS: In total, 261 patients were included. Of these, stage III patients accounted for 62.5% (163/261) at initial diagnosis, with 25.3% (66/261) at stage IIIB. Central-type non-small-cell lung cancer accounted for 61.7% (161/261). One hundred and forty patients underwent video-assisted thoracoscopic surgery and lobectomy accounted for 53.3% (139/261) of patients. Surgical time over average duration was defined as challenging surgeries, accounting for 43.7%. The postoperative complications rate of 261 patients was only 22.2%. Smoking history (odds ratio [OR] = 9.96, 95% [CI] 1.15-86.01, p = 0.03), chemoimmunotherapy (OR = 2.89, 95% CI 1.22-6.86, p = 0.02), and conversion to open surgery (OR = 11.3, 95% CI 1.38-92.9, p = 0.02) were identified as independent risk factors for challenging surgeries, while pneumonectomy (OR = 0.36, 95% CI 0.15-0.86, p= 0.02) was a protective factor. Meanwhile, pneumonectomy (OR = 7.51, 95% CI 2.40-23.51, p < 0.01) and challenging surgeries (OR = 5.53, 95% CI 1.50-20.62, p = 0.01) were found to be risk factors for postoperative complications greater than Clavien-Dindo grade 2. CONCLUSIONS: Compared to immunotherapy alone or in combination with apatinib, neoadjuvant chemoimmunotherapy could increase the difficulty of surgery while the incidence of postoperative complications remained acceptable. The conversion to open surgery and pneumonectomy after neoadjuvant immunotherapy should be reduced.

Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

The presence of micropapillary and/or solid subtypes is an independent prognostic factor for patients undergoing curative resection for stage I lung adenocarcinoma with ground-glass opacity.

Background: Non-predominant or even minimal micropapillary and/or solid (MP/S) subtypes have been reported to exert an unfavorable prognostic influence on surgically resected lung adenocarcinoma (ADC). Currently, there is a lack of evidence to demonstrate that high-grade pathological subtypes, including MP/S components, impact the prognosis of patients with surgically resected lung ADCs with ground-glass opacity (GGO). In this investigation, we explored the prognostic implications of minimal MP/S components in lung ADCs with GGO. Methods: A retrospective cohort study was conducted on 1,004 consecutive patients undergoing curative resection for pathologic stage (p-stage) I lung ADCs featuring GGO on computed tomography (CT) scans between January 2014 and December 2016. Tumors were categorized into MP/S positive (MP/S+) group and MP/S negative (MP/S-) group. MP/S+ tumors were defined when MP/S subtypes constituted ≥1% of the entire tumor. The prognostic impact of MP/S subtypes was evaluated using Kaplan-Meier analysis, Cox proportional hazard model and restricted cubic spine (RCS) model. Results: A total of 86 (8.6%) cases with MP/S+ tumors and 918 (91.4%) cases with MP/S- tumors were identified. The solid component tumor diameter and pathological invasive tumor size of MP/S+ tumors were both significantly larger than that of MP/S- tumors (13.0 vs. 4.0 mm, P<0.001, and 18.0 vs. 10.0 mm, P<0.001, respectively). After a median follow-up of 7.3 years, the presence of MP/S components was significantly associated with decreased RFS (5-year RFS, MP/S+ 88.3% vs. MP/S- 97.4%; P<0.001; HR =1.02). The presence of a histologic lepidic (Lep) component demonstrated a prognostic advantage in both MP/S- (5-year RFS, MP/S-Lep+ 98.0% vs. MP/S-Lep- 95.3%; P=0.01; HR =0.89) and MP/S+ subgroups (5-year RFS, MP/S+Lep+ 93.4% vs. MP/S+Lep- 83.2%; P=0.10; HR =0.84). MP/S+ components ≥5% were the only tumor-related factor that independently affected RFS [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.07-2.94] according to multivariate analysis. There was a progressively negative impact of the proportion of MP/S subtypes on RFS as illustrated by RCS model. Conclusions: The presence of MP/S patterns in stage I GGO-featured lung ADCs exhibit significant prognostic value and may have implications for tailored postoperative treatment and surveillance strategies, especially when the proportion exceeds 5% of the entire tumor.

A Polymeric Nanoparticle to Co-Deliver Mitochondria-Targeting Peptides and Pt(IV) Prodrug: Toward High Loading Efficiency and Combination Efficacy.

Developing combination chemotherapy systems with high drug loading efficiency at predetermined drug ratios to achieve a synergistic effect is important for cancer therapy. Herein, a polymeric dual-drug nanoparticle composed of a Pt(IV) prodrug derived from oxaliplatin and a mitochondria-targeting cytotoxic peptide is constructed through emulsion interfacial polymerization, which processes high drug loading efficiency and high biocompatibility. The depolymerization of polymeric dual-drug nanoparticle and the activation of Pt prodrug can be effectively triggered by the acidic tumor environment extracellularly and the high levels of glutathione intracellularly in cancer cells, respectively. The utilization of mitochondria-targeting peptide can inhibit ATP-dependent processes including drug efflux and DNA damage repair. This leads to increased accumulation of Pt-drugs within cancer cells. Eventually, the polymeric dual-drug nanoparticle demonstrates appreciable antitumor effects on both cell line derived and patient derived xenograft lung cancer model. It is highly anticipated that the polymeric dual-or multi-drug systems can be applied for combination chemotherapy to achieve enhanced anticancer activity and reduced side effects.

Genomic characteristics and immune landscape of super multiple primary lung cancer.

BACKGROUND: In recent years, a growing number of patients with multiple primary lung cancer (MPLC) are being diagnosed, and a subset of these patients is found to have a large number of lesions at the time of diagnosis, which are referred to as 'super MPLC'. METHODS: Here, we perform whole exome sequencing (WES) and immunohistochemistry (IHC) analysis of PD-L1 and CD8 on 212 tumor samples from 42 patients with super MPLC. FINDINGS: We report the genomic alteration landscape of super MPLC. EGFR, RBM10 and TP53 mutation and TERT amplification are important molecular events in the evolution of super MPLC. We propose the conception of early intrapulmonary metastasis, which exhibits different clinical features from conventional metastasis. The IHC analyses of PD-L1 and CD8 reveal a less inflamed microenvironment of super MPLC than that of traditional non-small cell lung cancer (NSCLC). We identify the potentially susceptible germline mutations for super MPLC. INTERPRETATION: Our study depicts the genomic characteristics and immune landscape, providing insights into the pathogenesis and possible therapeutic guidance of super MPLC. FUNDING: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Pathological response and tumor stroma immunogenic features predict long-term survival in non-small cell lung cancer after neoadjuvant chemotherapy.

PURPOSE: Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. METHODS: We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. RESULTS: Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. CONCLUSION: NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.

Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World).

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

SPOP negatively regulates mTORC1 activity by ubiquitinating Sec13.

The mammalian target of rapamycin complex1 (mTORC1) can response to amino acid to regulate metabolism and cell growth. GATOR2 act as important role in amino acid mediated mTORC1 signaling pathway by repressing GTPase activity (GAP) of GATOR1. However, it is still unclear how GATOR2 regulates mTORC1 signaling pathway. Here, we found that K63-ubiquitination of Sce13, one component of GATOR2, suppresses the mTORC1 activity by lessening the inter-interaction of GATOR2. Mechanistically, the ubiquitination of Sec13 was mediated by SPOP. Subsequently, the ubiquitination of Sec13 attenuated its interaction with the other component of GATOR2, thus suppressing the activity of mTORC1. Importantly, the deficiency of SPOP promoted the faster proliferation and migration of breast cancer cells, which was attenuated by knocking down of Sec13. Therefore, SPOP can act as a tumor suppressor gene by negatively regulating mTORC1 signaling pathway.

The activated plant NRC4 immune receptor forms a hexameric resistosome.

Innate immune responses against microbial pathogens in both plants and animals are regulated by intracellular receptors known as Nucleotide-binding Leucine-rich Repeats (NLR) proteins. In plants, these NLRs play a crucial role in recognizing pathogen effectors, thereby initiating the activation of immune defense mechanisms. Notably, certain NLRs serve as "helper" NLR immune receptors (hNLR), working in tandem with "sensor" NLR immune receptors (sNLR) counterparts to orchestrate downstream signaling events to express disease resistance. In this study, we reconstituted and determined the cryo-EM structure of the hNLR required for cell death 4 (NRC4) resistosome. The auto-active NRC4 formed a previously unanticipated hexameric configuration, triggering immune responses associated with Ca 2+ influx into the cytosol. Furthermore, we uncovered a dodecameric state of NRC4, where the coil-coil (CC) domain is embedded within the complex, suggesting an inactive state, and expanding our understanding of the regulation of plant immune responses. One Sentence Summary: The hexameric NRC4 resistosome mediates cell death associated with cytosolic Ca 2+ influx.

Monitoring circulating platelet activity to predict cancer-associated thrombosis.

A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to be a critical earlier trigger for cancer-associated thrombus formation. However, there currently is no viable approach to monitor specific changes in tumor-associated platelet activity. Here, we describe a chromatograph-like microfluidic device that is highly sensitive to the activity status of peripheral circulating platelets in both tumor-bearing mice and clinical cancer patients. Our results show a strongly positive correlation between platelet activation status and tumor progression. Six-month follow-up data from advanced cancer patients reveal positive links between platelet activity level and thrombus occurrence rate, with a high predictive capacity of thrombotic events (AUC = 0.842). Our findings suggest that circulating platelet activity status determined by this microfluidic device exhibits sensitive, predictive potential for thrombotic events in cancer patients for directing well-timed antithrombosis treatment.

Utility of 18F-FDG uptake in predicting major pathological response to neoadjuvant immunotherapy in patients with resectable non­small cell lung cancer.

PURPOSE: The aim of present study was to investigate the efficiency of 18F-FDG uptake in predicting major pathological response (MPR) in resectable non-small cell lung cancer (NSCLC) patients with neoadjuvant immunotherapy. METHODS: A total of 104 patients with stage I-IIIB NSCLC were retrospectively derived from National Cancer Center of China, of which 36 cases received immune checkpoint inhibitors (ICIs) monotherapy (I-M) and 68 cases with ICI combination therapy (I-C). 18F-FDG PET-CT scans were performed at baseline and after neoadjuvant therapy (NAT). Receiver-operating characteristic (ROC) curve analyses were conducted and area under ROC curve (AUC) was calculated for biomarkers including maximum standardized uptake value (SUVmax), inflammatory biomarkers, tumor mutation burden (TMB), PD-L1 tumor proportion score (TPS) and iRECIST. RESULTS: Fifty-four resected NSCLC tumors achieved MPR (51.9%, 54/104). In both neoadjuvant I-M and I-C cohorts, post-NAT SUVmax and the percentage changes of SUVmax (ΔSUVmax%) were significantly lower in the patients with MPR versus non-MPR (p < 0.01), and were also negatively correlated with the degree of pathological regression (p < 0.01). The AUC of ΔSUVmax% for predicting MPR was respectively 1.00 (95% CI: 1.00-1.00) in neoadjuvant I-M cohort and 0.94 (95% CI: 0.86-1.00) in I-C cohort. Baseline SUVmax had a statistical prediction value for MPR only in I-M cohort, with an AUC up to 0.76 at the threshold of 17.0. ΔSUVmax% showed an obvious advantage in MPR prediction over inflammatory biomarkers, TMB, PD-L1 TPS and iRECIST. CONCLUSION: 18F-FDG uptake can predict MPR in NSCLC patients with neoadjuvant immunotherapy.

A systematic review of image-guided, surgical robot-assisted percutaneous puncture: Challenges and benefits.

Percutaneous puncture is a common medical procedure that involves accessing an internal organ or tissue through the skin. Image guidance and surgical robots have been increasingly used to assist with percutaneous procedures, but the challenges and benefits of these technologies have not been thoroughly explored. The aims of this systematic review are to furnish an overview of the challenges and benefits of image-guided, surgical robot-assisted percutaneous puncture and to provide evidence on this approach. We searched several electronic databases for studies on image-guided, surgical robot-assisted percutaneous punctures published between January 2018 and December 2022. The final analysis refers to 53 studies in total. The results of this review suggest that image guidance and surgical robots can improve the accuracy and precision of percutaneous procedures, decrease radiation exposure to patients and medical personnel and lower the risk of complications. However, there are many challenges related to the use of these technologies, such as the integration of the robot and operating room, immature robotic perception, and deviation of needle insertion. In conclusion, image-guided, surgical robot-assisted percutaneous puncture offers many potential benefits, but further research is needed to fully understand the challenges and optimize the utilization of these technologies in clinical practice.

A prognostic and immunotherapeutic predictive model based on the cell-originated characterization of tumor microenvironment in lung adenocarcinoma.

Tumor microenvironment (TME) plays a crucial role in predicting prognosis and response to therapy in lung cancer. Our study established a prognostic and immunotherapeutic predictive model, the tumor immune cell score (TICS), by differentiating cell origins in lung adenocarcinoma (LUAD) based on the transcriptomic data of 2,510 patients in 14 independent cohorts, including 12 public datasets and two in-house cohorts. The high TICS was associated with prolonged overall survival (OS), especially in the early-stage LUAD. For the advanced-stage LUAD, high TICS predicted a superior OS in patients who were treated with immunotherapy instead of chemotherapy or TKI. The result suggested that TICS could serve as an indicator for the prognostic stratification management of patients in the early-stage LUAD, and as a potential guide for therapeutic decision-marking in the advanced-stage LUAD. Our findings provided an insight into prognosis stratification and potential guidance for treatment strategy selection.

Multiple primary lung cancer: Updates of clinical management and genomic features.

In recent decades, multiple primary lung cancer (MPLC) has been increasingly prevalent in clinical practice. However, many details about MPLC have not been completely settled, such as understanding the driving force, clinical management, pathological mechanisms, and genomic architectures of this disease. From the perspective of diagnosis and treatment, distinguishing MPLC from lung cancer intrapulmonary metastasis (IPM) has been a clinical hotpot for years. Besides, compared to patients with single lung lesion, the treatment for MPLC patients is more individualized, and non-operative therapies, such as ablation and stereotactic ablative radiotherapy (SABR), are prevailing. The emergence of next-generation sequencing has fueled a wave of research about the molecular features of MPLC and advanced the NCCN guidelines. In this review, we generalized the latest updates on MPLC from definition, etiology and epidemiology, clinical management, and genomic updates. We summarized the different perspectives and aimed to offer novel insights into the management of MPLC.

Effects of ultrasonic vibration on microstructure and mechanical properties of 1Cr12Ni3MoVN alloy fabricated by directed energy deposition.

Due to the rapid melting and solidification during directed energy deposition (DED) process, the defects and columnar crystals are likely to generate in the deposition layers, which reduce the quality and performance of the whole parts. Therefore, in order to improve the microstructure and mechanical properties of 1Cr12Ni3MoVN alloy manufactured by DED method, ultrasonic vibration (UV) has been employed to assist directed energy deposition process in this work. The results indicate that the high-intensity ultrasonic vibration can weaken the epitaxy growth tendency of crystal grains, and significantly improve plasticity while keeping an approximate strength. In addition, a two-dimensional numerical model is established to simulate the effect of ultrasonic vibration in the molten pool. The simulation results show that ultrasonic vibration remarkably improves the flow velocity and pressure in the molten pool, inducing the cavitation effect that breaks dendritic crystal and affects crystal characteristics. Meanwhile, the acoustic streaming effect changes the thermodynamic conditions and promotes high-temperature diffusion, which uniforms temperature distribution and reduces the temperature gradient in the molten pool. Thus the reduced temperature gradient G and raised solidification growth rate R promote the formation of fine equiaxed crystal characteristics after UV treatment. The product G × R increases and the ratio G/R decreases after UV treatment, resulting in the formation of fine equiaxed crystals.

The specific phagocytosis regulators could predict recurrence and therapeutic effect in thyroid cancer: A study based on bioinformatics analysis.

BACKGROUND: Thyroid cancer (TC) is one of the growing cancers and is prone to recurrence. Meanwhile, in immunotherapy, antibody-dependent cellular phagocytosis (ADCP) phagocytosis related regulators (PRs) play an important role. This study aims to investigate the prognostic value of specific PRs in TC. METHODS: The purpose of this study was to identify specific PRs in TC patients by retrieving RNA-seq and Clustered Regularly Interspaced Short Palindromic Repeats-cas9 data and an algorithm based on LASSO was used to construct the PRs-signature. Subsequently, prognosis value of PRs-signature for recurrence-free survival (RFS) was explored through various statistical analysis, including Cox regression analysis, Kaplan-Meier analysis, and receiver operating characteristic curve. Additionally, an analysis of immune cell content by risk group was conducted using CIBERSORT, single sample gene set enrichment analysis and MCP-counter algorithms, with a particular focus on the correlation between macrophages and specific PRs. RESULTS: We identified 36 specific PRs, and a PRs-signature was constructed using 5-prognostic PRs (CAPN6, MUC21, PRDM1, SEL1L3, and CPQ). Receiver operating characteristic analysis showed that predictive power of PRs-signature was decent, and the PRs risk score as an independent prognostic factor was found to be correlated with RFS showed by multivariate cox regression analysis. Meanwhile, a lower RFS was observed in the high-risk group than in the low-risk group. The results of the 3 algorithms suggested that our PRs-signature may have certain significance for macrophage content and ADCP. Interestingly, the low-risk group had higher levels of mRNA expression than the high-risk group at PDCD1, CTLA4, and pro-inflammatory factors from macrophage. CONCLUSION: For the purpose of prognostic management, this study developed a prediction model. And the cross-talk between certain PRs and TC patients was revealed in this study. Besides, the PRs-signature can predict the immunotherapy response, macrophage content, and ADCP status. TC patients will benefit from these developments by gaining insight into novel therapeutic strategies.

Treatments and whole exon sequencing of a case with multiple primary lung cancer.

INTRODUCTION: The number of patients with synchronous multiple primary lung cancer (sMPLC) has increased recently. However, diagnosing and selecting the appropriate therapeutic strategy for this type of disease is not simple. CASE PRESENTATION: This report presented a case of sMPLC with lymph node metastasis. With no smoking and cancer history, this patient had seven nodules in the right lung and underwent single-portal video-assisted thoracoscopic surgery (VATS). In addition, she received four cycles of chemotherapy after the operation. Whole exon sequencing (WES) was performed in five resected tissue samples (four tumors and one lymph node). We conducted genomic profiling and clone evolution analysis of the five samples. Gene detection helped to confirm that the metastasis lymph node was transferred from one nodule. There was apparent heterogeneity of gene mutations among the five samples of the patient, with only one shared "neurofilament heavy polypeptide" (NEFH) mutation. A dominant substitution of C > T/G > A was found in all the samples. Pyclone model was used to calculate all tissues' cellular prevalence (CP) values, and NEFH mutations were thought to be the ancestral clones. During the follow-up period, residual lesions showed no apparent changes and limited response to chemotherapy. CONCLUSIONS: This report showed an essential role in genomic detection and selecting the appropriate treatment of sMPLC. Surgery remains the primary treatment strategy for this type of disease, and the occurrence and development of sMPLC need more in-depth research.