Background: Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors. Methods: A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs. Result: NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs. Conclusion: In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.

Neutrophil extracellular traps (NETs) that are produced in the tumour microenvironment (TME) have been suggested to play an essential role in the dissemination of metastatic cancer under multiple infectious and inflammatory conditions. However, the functions of NETs in promoting non-small cell lung cancer (NSCLC) metastasis and the underlying mechanisms remain incompletely understood. Here, we found that NETs promoted NSCLC cell invasion and migration by inducing epithelial to mesenchymal transition (EMT). To explore how NETs contribute to NSCLC metastasis, microarrays were performed to identify substantial numbers of long noncoding RNAs (lncRNAs) and mRNAs that were differentially expressed in NSCLC cells after stimulation with NETs. Interestingly, we observed that the expression of lncRNA MIR503HG was downregulated after NETs stimulation, and ectopic MIR503HG expression reversed the metastasis-promoting effect of NETs in vitro and in vivo. Notably, bioinformatics analysis revealed that differentially expressed genes were involved in the NOD-like receptor and NF-κB signalling pathways that are associated with inflammation. NETs facilitated EMT and thereby contributed to NSCLC metastasis by activating the NF-κB/NOD-like receptor protein 3 (NLRP3) signalling pathway. Further studies revealed that MIR503HG inhibited NETs-triggered NSCLC cell metastasis in an NF-κB/NLRP3-dependent manner, as overexpression of NF-κB or NLRP3 impaired the suppressive effect of MIR503HG on NETs-induced cancer cell metastasis. Together, these results show that NETs activate the NF-κB/NLRP3 pathway by downregulating MIR503HG expression to promote EMT and NSCLC metastasis. Targeting the formation of NETs may be a novel therapeutic strategy for treating NSCLC metastasis.

Neutrophil extracellular traps (NETs) are closely related to cancer progression. NETs-related lncRNAs play crucial roles in non-small-cell lung cancer (NSCLC) but there have been no systematic studies regarding NETs-related long noncoding RNA (lncRNA) signatures to forecast the prognosis of NSCLC patients. It’s essential to build commensurate NETs-related lncRNA signatures. The expression profiles of prognostic mRNAs and lncRNAs and relevant clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The NETs-related genes came from the results of our transcriptome RNA microarray data. The co-expression network of lncRNAs and NETs-related genes was structured to confirm NETs-related lncRNAs. The 19 lncRNAs correlated with overall survival (OS) were selected by exploiting univariate Cox regression (P < 0.05). Lasso regression and multivariate Cox regression (P < 0.05) were utilized to develop a 12-NETs-related lncRNA signature. We established a risk score based on the signature, which suggested that patients in the high-risk group displayed significantly shorter OS than patients in the low-risk group (P < 0.0001, P = 0.0023 respectively in the two cohorts). The risk score worked as an independent predictive factor for OS in both univariate and multivariate Cox regression analyses (HR> 1, P< 0.001). Additionally, by RT-qPCR, we confirmed that NSCLC cell lines have higher levels of the three adverse prognostic NETs-related lncRNAs than normal lung cells. The expression of lncRNAs significantly increases after NETs stimulation. In short, the 12 NETs-related lncRNAs and their model could play effective roles as molecular markers in predicting survival for NSCLC patients.

The incidence of cancer in acromegaly patients may be higher than that in the general population, although this has not been fully elucidated yet. This study analyzed the risk of various important types of cancer in acromegaly patients. The study was registered in INPLASY (registration number: INPLASY202340037). The PubMed, Web of Science, and EMBASE databases were searched for studies based on strict inclusion and exclusion criteria, from the time of database inception up to June 30, 2022. All observational studies of acromegaly patients with cancer were included, without language restrictions. We used the Newcastle–Ottawa scale (NOS) checklist to assess the quality of evidence. A meta-analysis revealed the relationship between acromegaly and cancer using the standardized incidence rates (SIRs) and 95% confidence intervals (CIs) retrieved from the included studies. Nineteen studies were included and analyzed. The overall incidence of cancer (SIR = 1.45, 95%CI = 1.20–1.75), as well as that of thyroid (SIR = 6.96, 95%CI = 2.51–19.33), colorectal and anal (SIR = 1.95, 95%CI = 1.32–2.87), brain and central nervous system (SIR = 6.14, 95%CI = 2.73–13.84), gastric (SIR = 3.09, 95%CI = 1.47–6.50), urinary (SIR = 2.66, 95%CI = 1.88–3.76), hematological (SIR = 1.89, 95%CI = 1.17–3.06), pancreatic and small intestine (SIR = 2.59, 95%CI = 1.58–4.24), and connective tissue (SIR = 3.15, 95%CI = 1.18–8.36) cancers, was higher among patients with acromegaly than among the general population. No association between acromegaly and hepatobiliary, respiratory, reproductive, skin, breast, or prostate cancer was observed. This study demonstrated that acromegaly patients have a modestly increased chance of cancer as compared to the general population. Risk factors for cancer need to be further explored to monitor patients with acromegaly at a high risk for cancer more carefully.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive disease without standardized treatment strategies. The efficacy of second-line or beyond immune checkpoint inhibitors (ICIs) has been proven in recent studies, whereas the evidence for first-line immunotherapy for PSC is still limited to case reports and remains poorly understood.Materials and methods: This was a multicenter, retrospective analysis of 21 patients with a histological diagnosis of PSC who received ICI as first-line therapy from January 2019 to March 2022. The expression of PD-L1 was evaluated by immunohistochemistry (IHC) using the monoclonal antibody 22C3. Low and high PD-L1 expressions were defined using the tumor proportion score (TPS), with cutoffs of 1 and 50%, respectively.Results: All eight patients had PD-L1 positivity who underwent PD-L1 expression assessment, and six patients (6/8, 75.0%) had high PD-L1 expression. Among the 21 PSC patients, seven received tislelizumab, six received camrelizumab, four received sintilimab, three received pembrolizumab, and one received durvalumab. Among them, 18 PSCs received combination therapy, whereas another three PSCs received immunotherapy alone. Out of the 21 PSC patients, 12 (57.1%) achieved a partial response (PR), and five patients had stable disease (SD) as the best response, whereas four PSCs experienced dramatic progressive disease (PD). The median progression-free survival (PFS) was 9.2 (95% CI [4.3, 14.1]) months, and the median OS was 22.8 (95% CI [4.0, 41.5]) months. Among the three treatment groups (immunotherapy alone, immunotherapy combined with anlotinib, and chemoimmunotherapy), the median PFS was 8.0, 9.4, and 9.6 months, and the median OS was 19.0, 22.8, and 30.6 months, respectively. There was no difference in PFS and OS between the three treatment regimen groups (P = 0.86 and P = 0.34, respectively) and different immunotherapies (P = 0.10 and P = 0.23, respectively). No serious adverse events (grade ≥ 3) were noted.Conclusion: First-line immunotherapy has promising therapeutic potential in the treatment of PSC. More studies are warranted to confirm these findings.

The optimum granulocyte colony-stimulating factor (G-CSF) treatment for cancer patients after being treated with cytotoxic chemotherapy remains unknown. Therefore, a systematic review and Bayesian network meta-analysis were performed to assess the efficacy and tolerability of 11 G-CSF drugs on patients after chemotherapy. A total of 73 randomized controlled trials (RCTs) containing 15,124 cancer patients were included for the final network meta-analysis. Compared with pegfilgrastim, there were a higher risk with filgrastim for incidence of febrile neutropenia (FN) (OR [95% CI]: 1.63 [1.07, 2.46]), and a higher risk with short-acting G-CSF (S-G-CSF) biosimilar and lenograstim for incidence of bone pain (BP) (OR [95% CI]: 6.45 [1.10, 65.73], 5.12 [1.14, 26.12], respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim were best G-CSF drugs in reducing FN (cumulative probabilities: 58%, 15%, 11%, respectively). S-G-CSF biosimilar, empegfilgrastim, and long-acting G-CSF (L-G-CSF) biosimilar were best G-CSF drugs in reducing severe neutropenia (SN) (cumulative probabilities: 21%, 20%, 15%, respectively). Mecapegfilgrastim, balugrastim, lipegfilgrastim and L-G-CSF biosimilar were best G-CSF drugs in reducing BP (cumulative probabilities: 20%, 14%, 8%, 8%, respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim might be the most appreciate G-CSF drugs with both good efficacy and tolerability when treating cancer patients after cytotoxic chemotherapy.