BACKGROUND:Circulating tumor DNA (ctDNA)-based assays enable the detection of minimal residual disease (MRD) after surgery and are predictive of recurrence in lung cancer patients. However, the optimal technical strategy remains a subject of active debate. MATERIALS AND METHODS:We conducted a head-to-head comparison of tumor-naïve fixed panel, tumor-informed fixed panel, and tumor-informed personalized panel assays to analyze ctDNA-MRD in 417 plasma samples from 84 patients with stage I-III lung cancer. RESULTS:At the landmark time point, the personalized assay achieved superior performance compared with the tumor-naïve and tumor-informed assays, with a sensitivity of 40.9% (P = 0.003), a specificity of 100.0% (P < 0.001), a negative predictive value of 81.7% (P < 0.001), and a positive predictive value of 100.0% (P < 0.001). MRD positivity by the personalized assay predicted significantly shorter disease-free survival (P < 0.001; HR = 13.98; 95% CI: 1.95-100.37). Longitudinal MRD monitoring using personalized assay improved relapse prediction, providing median lead times of 7.0 months before radiologic recurrence. CONCLUSION:The personalized assays may optimize MRD detection and inform individualized postoperative surveillance in lung cancer.

Angiomatoid fibrous histiocytoma (AFH) is a rare mesenchymal tumor of intermediate malignant potential that predominantly affects young adults. The aim of this study was to highlight the clinicopathological features of AFH to assist with establishing a differential diagnosis. A 28-year-old female was referred to our department for diagnosis and treatment following identification of a 2.5 cm nodule near the hilum of the left upper pulmonary lobe on a computed tomography (CT) scan. She underwent a left upper lobe lobectomy via video-assisted thoracoscopy. On pathologic examination, the lesion measured 2.5 × 2.0 × 0.6 cm with a mitotic count of 0–2/10HPF, tumor necrosis of 0

Objective This study aims to compare postoperative survival outcomes between pathological stage IA pulmonary invasive mucinous adenocarcinoma (IMA) and invasive non-mucinous adenocarcinoma (INMA) and assess the effectiveness of sublobar resection in patients with stage IA IMA. Methods This study analyzed 113 patients with resected stage IA IMA (2015–2022) and 364 patients with resected stage IA INMA (2015–2019) from Guangdong Provincial People's Hospital. Propensity score matching (PSM) was applied to balance baseline characteristics. Survival curves were generated using the Kaplan–Meier method, and differences were evaluated with log-rank tests. Cox regression analysis was performed to identify predictors of survival. Results Before PSM, the IMA cohort exhibited a higher proportion of lower lobe foci (60.2 % versus 32.7 %; p < 0.001), a greater prevalence of stage IA1 disease (25.7 % versus 8.52 %; p < 0.001), and a lower frequency of sublobar resections (26.5 % versus 45.1 %; p = 0.001). Survival analysis demonstrated significantly reduced recurrence-free survival (RFS) and overall survival (OS) in patients with stage IA IMA compared to those with INMA (before PSM: RFS, p = 0.01; OS, p < 0.001; after PSM: RFS, p = 0.034; OS, p = 0.014). Pathological subtype and spread through air spaces were identified as independent predictors of RFS. Within the IMA group, statistically non-significant differences were observed between sublobar resection and lobectomy (before PSM: RFS, p = 0.17; OS, p = 0.27; after PSM: RFS, p = 0.71; OS, p = 0.37). Conclusion Patients with stage IA IMA exhibited inferior survival outcomes compared to those with stage IA INMA. No significant survival difference was observed between sublobar resection and lobectomy in patients with stage IA IMA.

Determining tumor progression status is critical for early-stage lung adenocarcinoma (esLUAD) diagnosis and treatment, yet histopathology-based grading often overlooks heterogeneity within grades. We propose RadioTrace, a deep contrastive learning framework integrating radiomic and pathological information to learn a radiomic trajectory for quantifying esLUAD progression. Across four multi-institutional cohorts, RadioTrace well predicted tumor phenotypes including spread through air spaces (STAS) and lymph node metastasis (LNM). Survival analyses demonstrated it as an independent prognostic factor (log-rank test p < 0.004 across all cohorts). Within the same pathological grade, it revealed significant survival heterogeneity (p < 0.02 across all cohorts), underscoring the limitations of current grading criteria. Genomic and transcriptomic analyses confirmed associations with progression-related molecular features. Longitudinal analysis of patients with multiple CT follow-ups further showed consistency with continuous progression. These findings demonstrate that RadioTrace enables quantitative, interpretable assessment of esLUAD progression, providing insights beyond histopathology and assisting clinical decision-making.

Background: Trastuzumab deruxtecan (T-DXd) significantly improves human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) outcomes. However, understanding of resistance mechanisms to T-DXd remains limited. Here, we present a case of a luminal B, HER2-positive MBC who displayed a partial response to T-DXd following five lines of prior HER2-targeted therapy but developed acquired resistance after 14 months of treatment. Organoid drug screening identified the potential strategy to overcome T-DXd resistance. Next-generation sequencing (NGS) of 550 cancer-associated genes was performed prior to T-DXd administration, and repeated after the emergence of T-DXd resistance. Case Description: We present a case of a luminal B, HER2-positive MBC. T-DXd was administered as the sixth-line regimen, resulting in a dramatic clinical response with near-complete resolution of the gluteal mass. After 14 months of therapy, the patient developed progressive cervical lymphadenopathy. Patientderived organoids were generated, and subsequent drug screening was performed, which identified anlotinib plus T-DXd as a potential candidate regimen. She was then treated with anlotinib and T-DXd and had disease control for 6 months before progressive liver metastases were observed. Genomic analysis further revealed aberrations in the ErbB signaling and cell cycle pathways that might be implicated in the emergence of T-DXd resistance. Conclusions: This case suggests that T-DXd resistance may be attributed to dysregulation in the ErbB signaling and cell cycle pathways. In vitro experiments are being conducted to ascertain the potential benefits of targeted inhibition of angiogenesis or cell cycle proteins in overcoming T-DXd resistance. Nevertheless, more cases and follow-up information are needed to support these views.

Neoadjuvant therapy has been widely used in breast cancer, but treatment response varies among individuals. We conducted multiomic profiling on tumor samples from 149 Chinese patients with breast cancer across ER-HER2+, ER+HER2+, and ER-HER2- subtypes, categorizing outcomes as pathologic complete response (pCR; n = 81) or residual disease (RD; n = 68). We identified distinct molecular features linked to pCR in each subtype: elevated cell proliferation in patients with ER-HER2- pCR, higher CDKN2A methylation in patients with ER-HER2- RD, increased KIT methylation in patients with ER-HER2+ RD, and MAP4K1 hypermethylation in patients with ER+HER2+ RD. These findings were subsequently validated in independent datasets. By integrating clinical and multiomic data, we developed MOPCR, a subtype-specific machine learning model that outperformed single-omic approaches in predicting treatment response. MOPCR demonstrated potential generalizability across cohorts and provided preliminary stratification of patient subgroups with higher pCR probability, offering valuable insights for precision cancer management.

Accurately assessing HER2-low (immunohistochemistry [IHC] 1 + and IHC 2+/in situ hybridization [ISH]–) and HER2-ultralow (IHC > 0 < 1+) is essential given the emergence of novel therapies. Thorough understanding of the reproducibility of rescoring IHC stained slides or re-staining archived tissue slides is essential. 2,869 breast cancer patients diagnosed between July 2021 and July 2022 from 10 hospitals in China were included in this multicentre study. The prevalence of different HER2 expression levels and distribution of HER2 IHC scores were assessed by HER2 status determination from rescored historical slides. Concordance was evaluated across historical results versus rescored results, historical results versus re-stained results, and leading center results versus local site results. Clinicopathological characteristics were retrospectively analyzed as well. HER2 IHC 0, IHC 1+, IHC 2+, and IHC 3 + were identified in 682 (23.8

Addressing the significant clinical challenges associated with managing malignant peripheral nerve sheath tumor (MPNST), this study focuses on the difficulties encountered in achieving accurate pathological diagnosis and the exploration of effective treatment options through genomic analysis. The study included 20 patients with an initial pathological diagnosis of MPNST. Next-generation sequencing-based genomic analysis was conducted to assess the molecular features of MPNST, specifically looking for somatic mutations and actionable mutations. The genomic analysis resulted in diagnostic refinement or reassignment for 20

OBJECTIVES:To propose a histological-grades-based Osseous Tumor Radiological and Interpretation and Management System (OT-RIMS) that would simplify the radiological evaluation of bone tumours, categorize key radiological features into severity levels, and inform corresponding patient management actions. METHODS:This retrospective study between January 2015 and August 2022 evaluated patients with solitary bone tumours confirmed by pathology and imaging follow-up received 2 or 3 imaging modalities of radiographs, CT, or MRI. Three radiologists independently assessed radiological features, categorized bone lesions based on OT-RIMS criteria, and reached a consensus. Kappa statistics and observed agreement were calculated. RESULTS:A total of 341 patients (mean age, 26.0 years; 159 women) were included, with 102 malignant, 177 benign, and 62 intermediate or low-grade malignant bone lesions. Sensitivity and specificity of readers 1, 2, and 3, respectively, in the identification of malignant tumours into OT-RIMS 4 were 93.1% (95 of 102) and 93.3% (223 of 239), 96.1% (98 of 102) and 91.6% (219 of 239), 92.2% (94 of 102) and 89.5% (214 of 239). Inter-reader agreement of OT-RIMS category for 3 readers was considered excellent (Kendall's W = 0.924, P < .001) with a kappa value of reproducibility in categories 1&2, 3, and 4 of 0.764, 0.528, and 0.930, respectively. CONCLUSIONS:The OT-RIMS category demonstrated excellent reproducibility despite the reader's expertise level in categorizing the risk stratification of bone tumours and informing patient management, with histological grades used as the reference standard. ADVANCES IN KNOWLEDGE:The OT-RIMS category reliably stratifies bone tumours into 4 categories corresponding to histological grades and standardized patient management.

Abstract Background: With Trastuzumab deruxtecan (T-DXd) changing the anti-HER2 treatment paradigm, HER2-low (defined as IHC2+/ISH- and IHC1+) breast cancer patients have emerged as a new targetable population. The lower threshold for HER2 expression that can benefit from HER2-directed antibody-drug conjugates (ADCs) is still being investigated, such as HER2 immunohistochemistry (IHC) &gt;0 to &lt; 1+ (defined as IHC 0 with incomplete and faint staining in ≤10% of tumor cells) in the DESTINY-Breast06 trial. Accurate determination of HER2 scores has become a critical topic in clinical discussions, given its clinical relevance to HER2-directed treatment strategies. Hence, we conduct this study (HER2-PATH, NCT05203458) to evaluate the distribution of HER2 status including HER2 IHC &gt;0 to &lt; 1+ in Chinese patients with breast cancer. Concordance between rescored and historical results was also analyzed. Methods: A retrospective study was conducted in breast cancer patients who underwent surgery at 10 sites in China between July 2021 and July 2022. Archived HER2 IHC slides from these patients were subjected to rescoring by a review committee comprising two readers and one adjudicator. The two readers independently evaluated each slide blinded to the historical scores. If their results matched, the recorded outcome was considered final. In cases of disagreement, the adjudicator made the final judgment. All slides were stained using Ventana 4B5 and scored following the ASCO/CAP 2018 guidelines, including the addition of the IHC &gt;0&lt; 1+ as defined in the DESTINY-Breast06 trial. The prevalence of the rescored HER2 status was calculated, and the concordance between the historical and rescored HER2 status was assessed using the Cohen's Kappa coefficient. Results: A total of 2868 patients were included in the analysis. The rescored results categorized 682 (23.8%) patients as HER2 IHC 0, 871 (30.4%) patients as IHC 1+, 800 (27.9%) patients as IHC 2+, and 515 (18.0%) patients as IHC 3+. The rates of HER2-positive, HER2-low, and HER2 IHC 0 (including HER2 null and HER2 IHC &gt;0 to &lt; 1+) were 21.8%, 54.3% and 23.9%, respectively. Notably, the prevalence of HER2-low was numerically higher in the HR-positive subgroup compared to the HR-negative subgroup (60.2% vs 30.6%). Furthermore, the prevalence of HER2 IHC &gt;0 to &lt; 1+ and HER2 null was 10.6% and 13.2% among all patients, respectively. Among the HR-positive subgroup, the prevalence of HER2 IHC &gt;0 to &lt; 1+ was 10.9%, while the rate was 9.1% among the HR-negative subgroup. Overall, there was an 83.1% concordance between the historical and rescored results for HER2 IHC scores. The concordance rate for IHC 1+ was numerically lower (74.5%) compared to IHC 0 (85.2%), IHC 2+ (81.4%), and IHC 3+ (98.6%). However, considering that 12.0% of IHC 1+ patients turned into IHC 2+ with limited impact on HER2-low diagnosis, the concordance rate for HER2-low remained as 91.6%. Conclusion: HER2-low prevalence in Chinese breast cancer patients was found to be consistent with global data, while additional 10.6% of patients were identified as HER2 IHC &gt;0 to &lt; 1+, which is currently being investigated in a randomized controlled trial comparing T-DXd with SoC. To our knowledge, this is the first study to report the prevalence of HER2-low, including HER2 IHC &gt;0 to &lt; 1+, in the Chinese breast cancer population based on rescored results. The concordance of HER2-low between the historical and rescored results was 91.6%, indicating that most cases could be reproducibly classified. Table: Rescored HER2 Expression Level Citation Format: Hong Lv, Junqiu Yue, Qingfu Zhang, Fangping Xu, Jianming Li, Lingfei Kong, Peng Gao, Guanjun Zhang, Haifeng Yang, Xiu Nie, Wen-Tao Yang. Prevalence of HER2-low and IHC &gt;0 to &lt; 1+ in breast cancer and its concordance between historical and rescored results: a multi-center, retrospective study in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-08.

Background: Triple-negative breast cancer (TNBC) stands out as the most aggressive form of breast cancer due to its significant propensity for metastasis. Exploring the molecular mechanisms of TNBC metastasis is essential to develop TNBC therapeutic strategies. Mex-3 RNA Binding Family Member A (MEX3A) has been recognized to promote TNBC proliferation. However, its role in TNBC metastasis hasn't been investigated. Methods: We investigated MEX3A levels in breast cancer cells, normal mammary tissues, and breast cancer tissues using Western blot analysis. Moreover, immunohistochemistry (IHC) analysis was used to determine MEX3A levels in TNBC tissues. Cell migration and invasion assays and lung metastasis assay were performed to investigate the role of MEX3A in TNBC metastasis in vitro and in vivo. Additionally, Co-immunoprecipitation was used to determine the interacting proteins of MEX3A. Results: MEX3A was upregulated in TNBC tissues compared to the normal mammary tissues, especially in TNBC tissues. Patients with high MEX3A expression exhibited shorter overall survival, distant metastasis-free-, relapse-free-, and post-progression survival time than those with low MEX3A expression (p < 0.05). MEX3A knockdown inhibited TNBC cell migration and invasion in vitro (p < 0.05). MEX3A overexpression promoted TNBC metastasis in vivo (p < 0.05). Mechanistically, MEX3A could interact with Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), resulting in activation of Ras GTPase (Ras-GTP), AKT Serine/Threonine Kinase (AKT), and Extracellular signal-regulated kinase (ERK) pathways, thereby promoting TNBC metastasis. Additionally, Ras pathway inhibitor MCP110 reversed the effect of MEX3A overexpression on TNBC cell migration and invasion. Conclusion: MEX3A is upregulated in TNBC tissues and can serve as an independent prognostic factor for TNBC patients. MEX3A promotes TNBC cell migration, invasion, and metastasis by interacting with NTRK1, resulting in the activation of Ras, AKT, and ERK pathways. These findings offer a potential therapeutic target for patients with TNBC.

Mammary mucoepidermoid carcinoma (MEC) is a rare entity. The molecular characteristics of breast MEC have not been fully investigated due to its rarity. We performed a retrospective study among 1000 patients with breast carcinomas and identified four cases of breast MEC. Clinical and demographic data were collected. Immunohistochemistry panels which were used to diagnose salivary gland MEC and breast carcinomas were also performed. MAML2 rearrangements were detected by FISH and fusion partners were identified by RNA sequencing. Whole-exome sequencing (WES) was used to reveal the genomes of these four breast MEC. Then, the biological functions and features of breast MEC were further compared with those of invasive breast carcinomas and salivary gland MEC. According to Ellis and Auclair’s methods, these four breast MEC could be classified as low-grade breast MEC. All the patients were alive, and disease-free survival (PFS) ranged from 20 months to 67 months. Among these four breast MEC, two cases were triple-negative, and the other two cases were found to be ER positive, with one also showing HER2 equivocal by immunohistochemical staining, but no amplification in FISH. FISH analysis confirmed the presence of the MAML2 translocation in three of four tumors, and CRTC1-MAML2 fusion was confirmed in two of them by RNA-sequencing. The average coverage size of WES for the tumor mutation burden estimation was 32 Mb. MUC4, RP1L1 and QRICH2 mutations were identified in at least three tumors, and these mutation also existed in breast invasive carcinoma databases (TCGA, Cell 2015; TCGA, Nature 2012). The results showed that there were many genes in breast MEC overlapping with the breast invasive carcinoma databases mentioned above, range from 5 to 63 genes (median:21 genes). Next, we assessed immune cell infiltration levels in these tumors. In all these tumors, M2 macrophages and plasma cell were in the high infiltration group. Our breast MEC showed different results from the salivary gland MEC, whose plasma cells were in the low infiltration group. Overall, we first analyzed the genomics and tumor microenvironment of breast mucoepidermoid carcinoma and proposed our hypothesis that although MECs arising in the breast resemble their salivary gland counterparts phenotypically, our findings indicate that breast MECs probably resemble invasive breast carcinomas at the genetic level and immune cell infiltration levels. More cases and in deep research need to be done to further understand this rare carcinoma.

Background Intraoperative assessment of tumor spread through air spaces (STAS) in early-stage lung adenocarcinomas (ADC) has been proposed to stratify patients for surgical management. However, data on the accuracy and reproducibility of detecting STAS on frozen sections (FS) and the prognostic value of STAS on FS remain limited and contradictory. Methods We conducted a retrospective study on the feasibility of intraoperative assessment of STAS by comparing the STAS patterns identified on FS and permanent sections from 524 patients diagnosed with pathologic stage 1 lung ADC. We also evaluated the association between STAS with patients’ clinicopathological characteristics and their postoperative survival outcomes. Results STAS was identified in 117 out of 524 patients (22.3 %) on permanent sections. Patients with STAS identified on permanent sections experienced shorter progression-free survival (PFS; P = 0.042) and overall survival (OS; P = 0.005) compared to those without. STAS was identified in 87 out of 509 patients on FS. Patients with STAS detected on FS also had shorter PFS (P = 0.010) and OS (P < 0.001) than those without. Compared to permanent sections, STAS detection on FS yielded 66.7 % (74/111) sensitivity, 96.7 % (385/398) specificity, 85.1 % (74/87) positive predictive value, 91.2 % (385/422) negative predictive value, and 90.2 % (459/509) overall agreement. The kappa coefficient was 0.688 (P < 0.001). Conclusions Our results from a large series of Chinese patients with stage 1 lung ADC indicated that STAS was associated with poorer survival outcomes on both FS and permanent sections. FS is a highly specific method for assessing STAS in stage 1 lung ADC, but caution is warranted regarding false-positive results.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

Background Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. Methods A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. Results The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably, patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). Conclusion A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

Introduction: Predicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs. Materials and methods: We retrospectively collected data from four cohorts of 874 patients diagnosed with biopsyproven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs. Results: The WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80). Conclusion: Our study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.

[目的]分析食管鳞癌患者(ESCC组)与健康对照组(HC组)肿瘤组织菌群多样性,筛选出食管鳞癌患者肿瘤组织中特异性细菌.[方法]收集105例食管鳞癌患者肿瘤组织标本和54例健康对照者的食管组织标本,提取标本总DNA,用PCR方法扩增16S rDNA V4区,后行高通量测序,将数据做OTU聚类及多样性分析筛选食管鳞癌组织内特征菌.最后用定量PCR(Q-PCR)扩增方法验证筛选结果.[结果]多样性分析表明ESCC组肿瘤标本和HC组正常食管组织标本内菌群多样性及组成存在明显差异,物种分析表明ESCC组以梭杆菌属(Fusobacterium)、孪生球菌属(Gemella)、奈瑟菌属(Neisseria)、卟啉单胞菌属(Porphyromonas)、链球菌属(Streptococcus)为主,HC组以梭杆菌属(Fusobacterium)、放线杆菌属(Actinobacillus)、链球菌属(Streptococcus)、普雷沃氏菌属(Prevotella)为主,LEfSe分析表明ESCC组卟啉菌属、梭杆菌属丰度升高,且具有统计学差异(P<0.05).Q-PCR验证结果表明食管鳞癌组织内牙龈卟啉单胞菌、具核梭杆菌拷贝数明显升高.[结论]食管癌肿瘤组织有其特征性的菌群组成,与健康对照组相比,食管鳞癌肿瘤组织中牙龈卟啉单胞菌、具核梭杆菌拷贝数明显升高,可能是其特征性的细菌.

Background: The current study attempted to describe the specific patterns of pathological tumor response and locoregional node metastases from surgically resected esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy (NAIC), as well as to explore the association between clinicopathological characteristics and such oncological patterns. Methods: Fifty-one patients with cT3 or deeper esophageal squamous cell cancer underwent subtotal esophagectomy after NAIC. The NAIC regimen included intravenous administration of platinum-based and docetaxel- and taxane-based chemotherapeutics along with a 200 mg fixed dose of one programmed death 1 (PD-1) inhibitor, given every 3 weeks. We divided patients into tumor/nodal good-responders and poor-responders based on the pathological observation of the tumor or nodal responses. We also examined the association between clinicopathological factors and tumor/nodal responses. Further, significant baseline predictors for tumor and nodal good-responders were identified using multivariate binary logistic regression. Results: Of the 51 patients, 68.6% achieved marked primary tumor response. Notably, 21.6% of patients achieved complete pathological response. Significant differences in treatment cycles between tumor good-responders and tumor poor-responders (P = 0.019) were observed. For locoregional nodal responses, only 33.3% of patients achieved down-staged nodal disease. Of the investigated variables, neoadjuvant cycles (odds ratio (OR): 5.271, 95% confidence interval (CI): 1.278 - 21.740, P = 0.022) and pretreatment platelets (OR: 0.979, 95% CI: 0.962 - 0.996, P = 0.017) were identified as independent predictors for good tumor and nodal responses. Conclusions: We conclusively noted that most patients receiving NAIC were tumor good-responders, whereas only one-third of patients were nodal good-responders. Furthermore, we identified that treatment cycle number and baseline platelet counts were independent predictors of combined tumor and nodal responses.