Clinicopathological characteristics and cancer-specific prognosis of primary pulmonary lymphoepithelioma-like carcinoma: a population study of the US SEER database and a Chinese hospital.

Introduction: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare histological type of non-small cell lung cancer (NSCLC), which accounts for less than 1% of NSCLC. Currently, there is no well-recognized treatment guideline for PPLELC. Methods: We identified PPLELC patients from the Surveillance, Epidemiology, and End Results (SEER) dataset between 2000 and 2015 (n = 72) as well as from our medical center between 2014 and 2020 (n = 16). All diagnoses were confirmed by pathological testing, and the clinicopathological characteristics of patients were retrieved and summarized. Survival analyses were conducted using the Kaplan-Meier analysis and log-rank tests. Multivariate survival analysis was performed with the Cox regression hazards model. Results: The median age at diagnosis of the PPLELC cohort was 64 years, ranging from 15 to 86 years. The percentages of patients with TNM stages I, II, III, and IV were 52.3%, 10.2%, 20.5%, and 17.0%, respectively. Among the 88 cases, lesion resection was performed in 69 cases (78.4%), 16 cases (18.1%) received beam radiation, and 40 cases (45.5%) underwent chemotherapy. In the SEER dataset of lung cancer, the percentage of PPLELC in the Asian race (0.528‰) was almost 10 times higher than that in the white (0.065‰) and black (0.056‰) races. Patients with TNM stage III-IV exhibited a worse prognosis than those with TNM stage I-II (p = 0.008), with a 5-year cancer-specific survival (CSS) rate of 81.8% for TNM stage I-II and 56.2% for TNM stage III-IV. Specifically, the N stage and M stage were the leading prognostic factors, not the T stage and tumor size. Moreover, patients who underwent surgery had significantly better outcomes than those who did not (p = 0.014). Additional multivariate analysis indicated that the TNM stage was an independent prognosis factor for CSS (HR, 3.31; 95% CI, 1.08-10.14). Conclusion: PPLELC is a rare tumor with Asian susceptibility. Although the prognosis of PPLELC is better than that of other subtypes of NSCLC, it remains unsatisfactory for advanced-stage disease. The current treatment options for PPLELC include surgical resection, chemotherapy, radiotherapy, and immune therapy. Among these options, patients with surgical resection have better survival rates in this study. However, large-scale clinical research trials will be necessary to develop effective treatment guidelines for PPLELC.

Causes of death and conditional survival estimates of long-term lung cancer survivors.

Introduction: Lung cancer ranks the leading cause of cancer-related death worldwide. This retrospective cohort study was designed to determine time-dependent death hazards of diverse causes and conditional survival of lung cancer. Methods: We collected 816,436 lung cancer cases during 2000-2015 in the SEER database, after exclusion, 612,100 cases were enrolled for data analyses. Cancer-specific survival, overall survival and dynamic death hazard were assessed in this study. Additionally, based on the FDA approval time of Nivolumab in 2015, we evaluated the effect of immunotherapy on metastatic patients' survival by comparing cases in 2016-2018 (immunotherapy era, n=7135) and those in 2013-2016 (non-immunotherapy era, n=42061). Results: Of the 612,100 patients, 285,705 were women, the mean (SD) age was 68.3 (11.0) years old. 252,558 patients were characterized as lung adenocarcinoma, 133,302 cases were lung squamous cell carcinoma, and only 78,700 cases were small cell lung carcinomas. TNM stage was I in 140,518 cases, II in 38,225 cases, III in 159,095 cases, and IV in 274,262 patients. 164,394 cases underwent surgical intervention. The 5-y overall survival and cancer-specific survival were 54.2% and 73.8%, respectively. The 5-y conditional survival rate of cancer-specific survival is improved in a time-dependent pattern, while conditional overall survival tends to be steady after 5-y follow-up. Except from age, hazard disparities of other risk factors (such as stage and surgery) diminished over time according to the conditional survival curves. After 8 years since diagnosis, mortality hazard from other causes became higher than that from lung cancer. This critical time point was earlier in elder patients while was postponed in patients with advanced stages. Moreover, both cancer-specific survival and overall survival of metastatic patients in immunotherapy era were significantly better than those in non-immunotherapy era (P<0.001), indicating that immunotherapeutic intervention indeed bring remarkable benefits to advanced lung cancer patients. Conclusions: Our findings expand on previous studies by demonstrating that non-lung-cancer related death risk becomes more and more predominant over the course of follow-up, and we establish a personalized web-based calculator to determine this critical time point for long-term survivors. We also confirmed the survival benefit of advanced lung cancer patients in immunotherapy era.

Inhibition of interleukin-13 gene expression by triptolide in activated T lymphocytes.

BACKGROUND AND OBJECTIVE: Triptolide, a type of diterpenoid, is the active compound of Tripterygium wilfordii; it plays roles in anti-inflammatory and immune response regulation. Our objective was to investigate the mechanism of the inhibitory effect of triptolide on interleukin-13 (IL-13) gene expression in activated T lymphocytes. Understanding the molecular mechanism by which triptolide exerts a therapeutic function may be useful in developing a pharmaceutical treatment for asthma. METHODS: Peripheral blood mononuclear cells (PBMC) and Hut-78 cells were stimulated with anti-CD3/CD28 with or without co-incubation with triptolide. The alteration of IL-13 messenger RNA (mRNA), expression and protein level were analysed using real-time reverse transcription polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, respectively. The intracellular distribution profile of transcription factor GATA3 and nuclear factor of activated T cells (NFAT1) were analysed by Western blotting. The binding rates of GATA3 and NFAT1 to the promoter sequence of IL-13 were analysed by chromatin immunoprecipitation (ChIP) PCR. RESULTS: In PBMC, the release of IL-13 was dependent on anti-CD3/CD28 stimulation. Its release could be inhibited by triptolide at the concentration of 500 nmol. In Hut-78 cells, IL-13 mRNA and protein expression were increased with anti-CD3/CD28 stimulation and significantly inhibited by incubation with 28 nmol triptolide. This concentration of triptolide also significantly inhibited the nuclear translocation of GATA3 and NFAT1 reducing the binding rate to the IL-13 gene promoter. CONCLUSIONS: Triptolide inhibits IL-13 gene transcription and protein expression by inhibiting GATA3 and NFAT1 nuclear translocation and their binding rates to the IL-13 gene promoter region.