ObjectiveTo investigate the CT signs and clinicopathological features of peripheral cavitary lung adenocarcinoma with the largest diameter less than or equal to 3 cm.Methods From January 2015 to December 2017, the CT signs and clinicopathological fertures of 51 patients with ≤3 cm peripheral cavitary lung adenocarcinoma diagnosed by chest CT and surgical pathology were retrospectively analyzed. Furthermore, CT signs and clinicopathological features of thick-walled cavitary lung adenocarcinoma and thin-walled cavitary lung adenocarcinoma were compared. There were 29 males and 22 females at age of 62 (56, 67) years.ResultsThere were 27 thick-walled cavitary lung adenocarcinoma and 24 thin-walled cavitary lung adenocarcinoma. Thick-walled cavitary adenocarcinoma had greater SUVmax [6.5 (3.7, 9.7) vs. 2.2 (1.4, 3.8), P=0.019], larger cavity wall thickness (11.8±4.6 mm vs. 7.6±3.7 mm, P=0.001), larger tumor tissue size [2.1 (1.7, 2.8) cm vs. 1.6 (1.2, 2.0) cm, P=0.006], and more solid nodules (17 patients vs. 8 patients, P=0.035). Thin-walled cavitary adenocarcinoma had more smoking history (12 patients vs. 6 patients, P=0.038), larger cavity size [12.3 (9.2, 16.6) mm vs. 4.4 (2.8, 7.1) mm, P=0.000], and larger proportion of cavities [0.30 (0.19, 0.37) vs. 0.03 (0.01, 0.09), P=0.000]. On CT signs, there were more features of irregular inner wall (19 patients vs. 6 patients, P=0.000), intra-cystic separation (16 patients vs. 6 patients, P=0.001) and vessels through the cystic cavity (10 patients vs. 1 patient, P=0.001) in thin-walled caviraty lung adenocarcinoma.ConclusionPeripheral cavitary lung adenocarcinoma of ≤3 cm on chest CT has characteristic manifestations in clinical, imaging and pathology, and there is a statistical difference between thick-walled cavitary lung adenocarcinoma and thin-walled cavitary lung adenocarcinoma.
Objective To analyze the expression of H2A histone family, member X (H2AFX) gene in lung adenocarcinoma and its influence on prognosis. Methods We analyzed the expression level of H2AFX gene in the tumor tissues (497 cases) and normal adjacent tissues (54 cases) of lung adenocarcinoma patients via The Cancer Genome Atlas. The patients were divided into high expression group and low expression group according to the expression level of H2AFX gene in lung adenocarcinoma samples. The relationship between H2AFX and clinicopathological features of patients was analyzed through logistic regression. Kaplan-Meier survival curve and log-rank test were used to study the correlation between H2AFX expression and the prognosis of lung adenocarcinoma patients. Univariate and multiple Cox regression analyses were performed to determine the prognostic significance of H2AFX expression in lung adenocarcinoma patients. The research also covered H2AFX-related pathways of genes in the development of lung adenocarcinoma with gene set enrichment analysis (GSEA). Results The H2AFX expression was higher in lung adenocarcinoma tissues than that in normal adjacent tissues (P<0.001). Besides, it was significantly correlated with age (P<0.001), T staging (P=0.007), and N staging (P=0.010), but had little to do with M staging or gender (P>0.05). Kaplan-Meier survival curve and log-rank test showed that the survival rate of patients with high H2AFX expression was vastly lower than that of patients with low H2AFX expression (P<0.001). Multiple Cox regression analysis demonstrated that H2AFX could be an independent prognostic factor for lung adenocarcinoma [hazard ratio=1.41, 95% confidence interval (1.11, 1.78), P=0.004]. The results of GSEA displayed that H2AFX was involved in cell cycle, homologous recombination, DNA replication, base excision and repair, spliceosome, mismatch repair, p53 signaling pathway, nucleotide excision and repair, RNA degradation, RNA polymerase, and other pathways. Conclusions The expression of H2AFX gene is high in lung adenocarcinoma, and closely connected to the prognosis, occurrence, and evolution of lung adenocarcinoma. This gene can be one of the new molecular markers and therapeutic targets for lung adenocarcinoma.
ObjectiveTo investigate the value of serum soluble CD146 (sCD146) in determining acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in lung adenocarcinoma.MethodsA total of 144 lung adenocarcinoma EGFR sensitive patients in People’s Hospital of Zhengzhou University diagnosed from January 2016 to December 2016 were recruited in the study. According to the different time of taking drugs, the patients were divided into a non-medication group (31 cases), a 1 to 3 month treatment group (25 cases), a 4 to 6 month treatment group (19 cases), a 7 to 12 month treatment group (25 cases), a drug-resistant group (24 cases), and a nonresistant group up to 1 year of treatment (20 cases). The serum levels of sCD146, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured by ELISA and chemiluminescence and compared between different period of medication. The relationship of serum sCD146 with tumor markers (CEA, NSE) and tumor related clinical parameters (age, gender, tumor stage, metastasis, tumor diameter, number of the lesions) were analyzed.ResultsThe serum sCD146 level was minimum in the non-medication group that did not receive pioglitazone treatment, highest in the 1 to 3 month treatment group (early treatment period), and declined with duration of medication until resistance occurred without significant difference (P>0.05). The level of sCD146 of the drug-resistant group was significantly lower than that of all nonresistant groups, with significant difference (allP<0.05), but still higher than that of the non-medication group (P<0.05). The serum sCD146 levels in the nonresistant patients with medication over 1 year and within 1 year were similar (P>0.05), and significantly higher than the non-medication group and drug-resistance group (allP<0.05). The serum CEA levels did not differ significantly between 6 groups (P>0.05). The serum NSE level of the 4 to 6 month treatment group was lower than that of the 7 to 12 month treatment group (P<0.05), but both in the normal reference range. The NSE levels did not differ in any other groups (P>0.05). Serum sCD146 was associated with metastasis (P<0.05), but not associated with serum CEA or NSE, nor with sex, age, tumor staging, tumor diameter or lesion number (allP>0.05).ConclusionsCD146 may be involved in the mechanism of TKI killing tumor cells and the mechanism of TKI resistance, and may be a serological marker for monitoring the efficacy of TKI and judging the resistance of TKI.
ObjectiveTo investigate the correlation between histological subtypes of invasive lung adenocarcinoma and epithelial growth factor receptor (EGFR) gene mutation, and to provide a reference for clinical prediction of EGFR gene mutation status.MethodsFrom October 2017 to May 2019, 102 patients with invasive lung adenocarcinoma were collected, including 58 males and 44 females aged 62 (31-84) years. Invasive lung adenocarcinoma was classified into different histological subtypes. Scorpion probe amplification block mutation system (ARMS) real-time PCR was used to detect the mutation of EGFR gene in adenocarcinoma specimens, and the relationship between invasive lung adenocarcinoma subtypes and EGFR mutation status was analyzed.ResultsIn 102 patients with invasive lung adenocarcinoma, EGFR gene mutations were detected in 68 patients, and the mutation rate was 66.7% (68/102). The mutation sites were mainly concentrated in the exons 19 and 21; the mutation rate was higher in female patients (34/44, 77.3%) and non-smokers (34/58, 58.6%). EGFR mutation was mostly caused by acinar-like invasive lung adenocarcinoma, and was rare in solid-type lung adenocarcinoma. The EGFR gene mutation rates in different subtypes of adenocarcinoma were statistically different (P<0.05).ConclusionThe EGFR mutation status is related to gender, smoking status and histological subtype of invasive lung adenocarcinoma. EGFR mutation rates are higher in female, non-smoking and acinar-like invasive lung adenocarcinoma patients, and are lower in patients with solid type lung adenocarcinoma.
Objective To investigate the clinical and pathological characteristics, prognosis and treatment strategies of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). Methods We retrospectively analyzed the clinical data of 489 patients with AIS and MIA in our hospital from January 2007 to August 2015. There were 122 males and 367 females with an average age of 26–78 (51±9) years. According to the pathological types, they were divided into the AIS group (246 patients) and the MIA group (243 patients). In the AIS group, there were 60 males and 186 females with an average age of 50±7 years. In the MIA group, there were 62 males and 181 females with an average age of 54±5 years. The clinicopathological features, surgical methods and prognosis of the two groups were compared. Results There were significant differences in age, value of carcino-embryonic antigen (CEA), nodule shape and nodule size between the AIS and MIA groups (P<0.05). AIS patients were mostly under the age of 60 years with the value of CEA in the normal range which often appeared as pure ground-glass opacity lung nodules <1 cm in diameter on the CT scan. MIA often appeared as mixed ground-glass nodules <1.5 cm in diameter, accompanied by bronchiectasis and pleural indentation. The 5-year disease-free survival rate of the AIS and MIA groups reached 100%, and there was no statistical difference in the prognosis between the two groups after subtotal lobectomy (pulmonary resection and wedge resection) and lobectomy, systematic lymph node dissection and mediastinal lymph node sampling. Conclusion The analysis of preoperative clinical and imaging features can predict the AIS and MIA and provide individualized surgery and postoperative treatment program.
ObjectiveTo explore the accuracy of machine learning algorithms based on SHOX2 and RASSF1A methylation levels in predicting early-stage lung adenocarcinoma pathological types. MethodsA retrospective analysis was conducted on formalin-fixed paraffin-embedded (FFPE) specimens from patients who underwent lung tumor resection surgery at Affiliated Hospital of Nantong University from January 2021 to January 2023. Based on the pathological classification of the tumors, patients were divided into three groups: a benign tumor/adenocarcinoma in situ (BT/AIS) group, a minimally invasive adenocarcinoma (MIA) group, and an invasive adenocarcinoma (IA) group. The methylation levels of SHOX2 and RASSF1A in FFPE specimens were measured using the LungMe kit through methylation-specific PCR (MS-PCR). Using the methylation levels of SHOX2 and RASSF1A as predictive variables, various machine learning algorithms (including logistic regression, XGBoost, random forest, and naive Bayes) were employed to predict different lung adenocarcinoma pathological types. ResultsA total of 272 patients were included. The average ages of patients in the BT/AIS, MIA, and IA groups were 57.97, 61.31, and 63.84 years, respectively. The proportions of female patients were 55.38%, 61.11%, and 61.36%, respectively. In the early-stage lung adenocarcinoma prediction model established based on SHOX2 and RASSF1A methylation levels, the random forest and XGBoost models performed well in predicting each pathological type. The C-statistics of the random forest model for the BT/AIS, MIA, and IA groups were 0.71, 0.72, and 0.78, respectively. The C-statistics of the XGBoost model for the BT/AIS, MIA, and IA groups were 0.70, 0.75, and 0.77, respectively. The naive Bayes model only showed robust performance in the IA group, with a C-statistic of 0.73, indicating some predictive ability. The logistic regression model performed the worst among all groups, showing no predictive ability for any group. Through decision curve analysis, the random forest model demonstrated higher net benefit in predicting BT/AIS and MIA pathological types, indicating its potential value in clinical application. ConclusionMachine learning algorithms based on SHOX2 and RASSF1A methylation levels have high accuracy in predicting early-stage lung adenocarcinoma pathological types.
Lung adenocarcinoma has become the most common type of lung cancer. According to the 2015 World Health Organization histological classification of lung cancer, invasive lung adenocarcinoma can be divided into 5 subtypes: lepidic, acinar, papillary, solid, and micropapillary. Relevant studies have shown that the local lobectomy or sublobectomy is sufficient for early lepidic predominant adenocarcinoma, while lobectomy should be recommended for tumors containing micropapillary and solid ingredients (≥5%). Currently, the percentage of micropapillary and solid components diagnosed by frozen pathological examination is 65.7%, and the accuracy of diagnosis is limited. Therefore, to improve the accuracy of diagnosis, it is necessary to seek new methods and techniques. This paper summarized the characteristics and rapid diagnosis tools of early lung adenocarcinoma subtypes.
ObjectiveTo evaluate the clinical manifestation, radiological, pathological features and treatment of organizing pneumonia (OP) induced by aerosolized recombinant super compound interferon (rSIFN-co). MethodsClinical features and related laboratory examinations of a patient with OP developing after initiation of rSIFN-co for treatment of lung adenocarcinoma were analyzed, and the relevant literature was reviewed. ResultsA 48-year-old man developed cough, fevers, shortness of breath and weight loss, shortly half a month after initiation of therapy with rSIFN-co for lung adenocarcinoma. Chest high resolution computerized tomography (HRCT) showed multiple lung infection diseases. However, the anti-infection treatment was invalid. Lung tissue biopsy by bronchofibroscope was consistent with OP. After discontinuation of rSIFN-co and receiving pulse corticosteroid therapy followed by oral methylprednisolone, the pneumonic symptoms and chest manifestations markedly improved. After eight-month follow-up, the patient's condition was stable. The relative literature screening from Pubmed and Wanfangdata was implemented, but there was no report about OP caused by aerosolized rSIFN-co for lung adenocarcinoma. ConclusionThis report suggests that treatment with aerosolized rSIFN-co for lung adenocarcinoma may induce OP, a rare complication, and clinicians should have vigilance on it.
Computed tomography (CT) imaging is a vital tool for the diagnosis and assessment of lung adenocarcinoma, and using CT images to predict the recurrence-free survival (RFS) of lung adenocarcinoma patients post-surgery is of paramount importance in tailoring postoperative treatment plans. Addressing the challenging task of accurate RFS prediction using CT images, this paper introduces an innovative approach based on self-supervised pre-training and multi-task learning. We employed a self-supervised learning strategy known as “image transformation to image restoration” to pretrain a 3D-UNet network on publicly available lung CT datasets to extract generic visual features from lung images. Subsequently, we enhanced the network’s feature extraction capability through multi-task learning involving segmentation and classification tasks, guiding the network to extract image features relevant to RFS. Additionally, we designed a multi-scale feature aggregation module to comprehensively amalgamate multi-scale image features, and ultimately predicted the RFS risk score for lung adenocarcinoma with the aid of a feed-forward neural network. The predictive performance of the proposed method was assessed by ten-fold cross-validation. The results showed that the consistency index (C-index) of the proposed method for predicting RFS and the area under curve (AUC) for predicting whether recurrence occurs within three years reached 0.691 ± 0.076 and 0.707 ± 0.082, respectively, and the predictive performance was superior to that of existing methods. This study confirms that the proposed method has the potential of RFS prediction in lung adenocarcinoma patients, which is expected to provide a reliable basis for the development of individualized treatment plans.
Recently, an editorial in Cell Research illuminated the concept of the curative time window for lung adenocarcinoma. Within this window, patients could achieve 100.0% 5-year or 10-year post-operative recurrence-free survival. Adenocarcinoma in situ and minimally invasive adenocarcinoma in pathology, as well as pure ground-glass opacity in radiology could be regarded as the curative time window. However, not all the patients can catch this time window. A precise understanding of this concept helps elevate the curative rate for lung cancer patients and mitigate the risks of overdiagnosis and overtreatment. This article delves into the accurate comprehension of the surgical curative time window for lung adenocarcinoma, proposed a clinical strategy for early-stage lung adenocarcinoma, and introduced clinical procedures comprising of this time window. It offers fresh insights into the timing of surgical interventions for lung adenocarcinoma.