OBJECT: To investigate the association of R-loop binding proteins with prognosis and chemotherapy efficacy in lung adenocarcinoma. METHODS: The data related to R-loop regulatory genes were obtained from literature of R-loop proteomics and relevant databases. We used 403 lung adenocarcinoma cases in the Cancer Genome Atlas as training set, and two datasets GSE14814 and GSE31210 in Gene Expression Omnibus as validation sets. The weighted gene co-expression network analysis (WGCNA) was employed to identify R-loop genes with a significant impact on the clinical phenotype of lung adenocarcinoma. Least absolute shrinkage and selection operator (LASSO) regression was utilized to eliminate genes exhibiting multicollinearity. A multivariate Cox proportional hazards model was employed to scrutinize clinical variables and R-loop characteristic genes that exert independent prognostic effects on patient survival. Subsequently, a risk score model was constructed. The predictive capacity of this model for the prognosis of patients was analyzed and validated. Additionally, the performance of risk model on the anti-neoplastic drug sensitivity was assessed. The mutations of R-loop gene were analyzed by maftools. The effect of PLEC expression on anti-tumor drug sensitivity was tested on non-small cell lung adenocarcinoma H1299 and A549 cells in vitro. RESULTS: A collection of 1551 R-loop genes were obtained, and 78 genes exhibited significant effects on the clinical phenotype shown on WGCNA. The LASSO regression analysis retained 14 R-loop genes. A multivariate Cox analysis further identified 3 R-loop genes (HEXIM1, GLI2, PLEC) and a clinical variable (tumor grading) that were associated with patient prognosis. Risk prediction model was established according to the regression coefficients of each parameter. Kaplan-Meier survival analysis showed that the prognosis of high-risk group patients was significantly worse than that of low-risk group (P<0.01). The time-dependent ROC curve showed that the risk model had good predictive ability in both training and validation sets. Predictive analyses of anti-neoplastic drug sensitivity indicated a diminished responsiveness to both chemotherapy and targeted treatment drugs among high-risk patients. The expression of PLEC was strongly correlated with the sensitivity of gefitinib, a classical EGFR inhibitor. CONCLUSIONS: R-loop binding proteins have been identified as significant determinants in the prognosis and therapeutic strategies for lung adenocarcinoma. The results indicates that therapeutic interventions targeting these specific R-loop binding proteins might contribute to a better survival in lung cancer patients.
目的: 研究R环结合蛋白对肺腺癌预后与抗肿瘤药物敏感性的影响，为R环在肿瘤生物学中的调控机制研究与临床决策提供科学依据。方法: 从R环结合蛋白质组学研究文献与相关数据库中获取R环结合基因，以癌症基因组图谱数据库中的403例肺腺癌病例的数据作为训练集，以基因表达综合数据库中GSE14814与GSE31210两个数据集的数据作为验证集，采用加权基因共表达网络分析（WGCNA）、最小绝对收缩和选择算子（LASSO）、多因素Cox比例风险模型逐步筛选具有独立预后作用的临床变量与R环特征基因，Maftools分析R环特征基因的突变特征，构建基于R环特征基因的风险评分和列线图模型，验证该模型对高低分险亚型患者预后预测的能力及其对抗肿瘤药物治疗敏感性的影响。最后采用实验验证R环特征基因表达对抗肿瘤药物敏感性的影响。结果: 收集整理得到R环基因1551条，WGCNA筛选得到显著影响临床表型的R环基因78条，LASSO回归保留R环基因14条，多因素Cox筛选到三个与患者预后密切相关的R环基因（HEXIM1、GLI2、PLEC）和一个临床变量（肿瘤分级），根据各参数的回归系数构建预后模型与列线图模型。Kaplan-Meier生存分析显示，高风险组患者预后明显差于低风险组（P<0.01）。时间依赖受试者工作特征曲线表明，该模型在训练集和验证集列队中均具有较好的预测能力。抗肿瘤药物敏感性预测结果表明，高风险组患者对肺癌化疗与靶向治疗药物的敏感性更低。PLEC基因沉默实验表明抑制PLEC的表达能增强表皮生长因子受体野生型非小细胞肺腺癌细胞株对吉非替尼的敏感性。结论: R环结合蛋白是肺腺癌预后的风险因素，联合临床信息和R环特征基因可以有效预测肺腺癌预后，靶向上述R环特征基因可能对提高患者存活率具有重要意义。.

After the recommendation of computed tomography as a routine procedure for lung cancer screening, an increasing number of young adults have been diagnosed with pulmonary ground-glass opacity (GGO). Up to 63% of pulmonary nodules with a GGO component can be malignant. Since young cancer patients have limited exposure to environmental mutagens, they have special characteristics and needs. This study sought to compare the clinicopathological characteristics of young and old patients with GGO-associated lung adenocarcinoma (GGO-LUAD). Clinicopathological data from 203 patients who underwent video-assisted thoracoscopic surgery between January 2018 and April 2020 for pulmonary GGO component nodules were reviewed. Lung nonmucinous adenocarcinoma patients younger than 40 years old and older than 40 years old were enrolled: 103 patients ≤ 40 years old and 100 patients > 40 years old. The relevant clinicopathological features, including sex, smoking status, tumor size, pathological characteristics, radiographic features and prognosis of pulmonary nodules, were evaluated. Univariate analyses were applied for comparisons between groups. The differences in baseline characteristics (sex, smoking status, tumor location) between the different age groups were not significant. Young patients were more likely to have tumors < 1 cm in size, while older patients predominantly had tumors > 2 cm in size. The mean percentage of invasive adenocarcinoma was greater in the elderly group. Young and older patients seemed to have similar subtypes of adenocarcinoma (p > 0.05) but had different degrees of differentiation (p < 0.001). The 3-year overall survival (OS) and recurrence-free survival (RFS) of the young group were 100% and 99.03%, respectively, while the 3-years OS and RFS of the older group were 99% and 98%, respectively. Our work revealed that young patients with malignant pulmonary nodules and GGOs have distinct pathological subtypes. Patients with GGOs of different ages have different clinicopathological characteristics. The 3-year prognosis of young patients with malignant pulmonary nodules with GGOs is satisfactory.

Lung cancer metastasizing to the colon is exceedingly rare and can present similarly to colorectal cancer. It is crucial to conduct further evaluations using immunohistochemical (IHC) stains and genomic testing to differentiate between the two and provide appropriate treatment without delay. Lung cancer generally has a poor prognosis, especially in cases with distant metastases. Although gastrointestinal (GI) metastases from lung cancer have been reported, cases of lung cancer manifesting as colon metastasis are extremely rare, with only a few instances documented.

This case emphasizes the significance of recognizing and managing Brevibacterium species. Here, we present a unique case of Brevibacterium species isolated from the cerebrospinal fluid of a 60-year-old female with recently diagnosed human immunodeficiency virus (HIV) and small cell carcinoma of the lung. Management involved a two-week course of intravenous vancomycin. Brevibacterium species are infrequently encountered in clinical practice. Sharing this case report aims to enhance the limited understanding of Brevibacterium species infections and encourages discussion among healthcare professionals regarding its diagnosis and management.

Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between palliative measures and surgery. This case indicates that total talar replacement is an effective intervention for localized talar metastases and highlights the importance of early intervention. A 48-year-old man was diagnosed with a pathologic talar fracture due to talar metastases was observed after 8 years of chemotherapy following a diagnosis of lung adenocarcinoma. Despite radiotherapy, the patient\'s activities of daily living (ADLs) deteriorated due to pain on walking, prompting a request for surgical intervention. Total talar replacement was performed, allowing the patient to begin full weight-bearing ambulation 2 weeks post-operatively. Total talar replacement appears to be an effective treatment for localized talar metastases and should be performed as early as possible.

UNASSIGNED: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease.
UNASSIGNED: We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery.
UNASSIGNED: This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.

A 67-year-old man with cervical spondylotic myelopathy undergoing conservative treatment presented with subacute progression of fine motor and ambulatory disturbances, leading to admission at a previous hospital. Pre-cervical laminoplasty chest computed tomography (CT) revealed a tumor in the left upper lobe of the lung, prompting transfer to our institution. Transbronchial biopsy findings were consistent with adenocarcinoma, diagnosed as clinical stage T2bN0M0, Stage IIA. The neurological abnormalities could not be solely attributed to cervical spondylotic myelopathy, leading to a diagnosis of concurrent paraneoplastic neurological syndrome (PNS). During hospitalization, the patient\'s condition progressed to a state of constant bed rest within two weeks. On the 17th hospital day, a left upper lobectomy was performed, resulting in significant improvement, allowing the patient to ambulate with assistance after two weeks, and transfer to a convalescent rehabilitation hospital on the 58th hospital day. Subsequent cancer multigene panel testing revealed a positive MET exon 14 skipping mutation. Given the absence of reports on this mutation in lung adenocarcinoma associated with PNS, we consider it rare and thus report this case.

BACKGROUND: Large amino acid transporter type 1 (LAT1) provides cancer cells with essential amino acids for both protein synthesis and cell growth and may predict patient prognosis. Additionally, LAT1 inhibition can be a therapeutic target. This study aimed to examine the prognostic significance of LAT1 expression in lung cancer, paying special attention to adenocarcinoma subtypes.
METHODS: Tissue microarrays (TMA) of 1,560 total cores obtained from surgically resected lung cancer specimens between 1995 and 2008 at our hospital were used. Overall, 795 cases of adenocarcinoma were identified, and 717 underwent further evaluation. Immunohistochemical staining of whole slides and TMA cores were assessed to set H-score cutoff value.. Immunohistochemical expression of LAT1 was examined based on the subtypes of adenocarcinoma. Statistical analyses explored the prognostic significance of LAT1.
RESULTS: Adenocarcinoma accounted for 71.8% of all cases (n = 795), and 216 cases (27.1%) expressed LAT1. The 795 cases were categorized into five subtypes: lepidic (n = 29, 3.6%), papillary (n = 601, 75.6%), acinar (n = 58, 7.3%), and solid (n = 9, 1.1%); 717 of the 795 cases were further assessed according to the exclusion criteria. The LAT1-positive ratio increased as the architectural grade increased. Notably, in papillary adenocarcinoma, the LAT1-positive group had significantly lower overall survival compared to the negative group (10-year survival: 45.6% vs. 60.8%, p < 0.001).
CONCLUSIONS: LAT1 expression was higher in high-grade subtypes of pulmonary adenocarcinoma. Moreover, LAT1 expression is useful for predicting prognosis, particularly in papillary adenocarcinoma, facilitating prognostic stratification of papillary adenocarcinoma.

Among mucus-producing lung cancers, invasive mucinous adenocarcinoma of the lung is a rare and unique subtype of pulmonary adenocarcinoma. Notably, mucus production may also be observed in the five subtypes of adenocarcinoma grouped under the higher-level diagnosis of Invasive Non-mucinous Adenocarcinomas (NMA). Overlapping pathologic features in mucus-producing tumors can cause diagnostic confusion with significant clinical consequences. In this study, we established lung tumoroids, PDT-LUAD#99, from a patient with NMA and mucus production. The tumoroids were derived from the malignant pleural effusion of a patient with lung cancer and have been successfully developed for long-term culture (> 11 months). Karyotyping by fluorescence in situ hybridization using an alpha-satellite probe showed that tumoroids harbored aneuploid karyotypes. Subcutaneous inoculation of PDT-LUAD#99 lung tumoroids into immunodeficient mice resulted in tumor formation, suggesting that the tumoroids were derived from cancer. Xenografts from PDT-LUAD#99 lung tumoroids reproduced the solid adenocarcinoma with mucin production that was observed in the patient\'s metastatic lymph nodes. Immunoblot analysis showed MUC5AC secretion into the culture supernatant of PDT-LUAD#99 lung tumoroids, which in contradistinction was barely detected in the culture supernatants of NCI-A549 and NCI-H2122 pulmonary adenocarcinoma cells known for their mucin-producing abilities. Here, we established a novel high-mucus-producing lung tumoroids from a solid adenocarcinoma. This preclinical model may be useful for elucidating the pathogenesis of mucus-producing lung cancer.

Biliothorax is the presence of bile in the pleural cavity. This condition is rare, and it usually results as a complication of hepatobiliary procedures. The authors present a case of an 87-year-old female who was admitted to the emergency department with the acute onset of severe dyspnea. A chest X-ray and CT revealed a large right-lung pleural effusion that, after thoracentesis, confirmed the presence of biliothorax. It is important to consider this entity when confronted with an effusion liquid of a dark greenish color, as a delay in diagnosis and management may be life-threatening.