Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions : Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the most frequently used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different stages of PDAC, 75 patients with benign pancreatic disease, and 74 healthy individuals. All samples were randomly divided into a training set and a validation set. Carbohydrate antigen 19.9, CA242, POSTN, as well as carcinoembryonic antigen, were measured by ELISA or automated immunoassay. The receiver operating characteristic curve analysis revealed that the performance of CA19.9 in the validation group were improved by the marker panel composed of CA19.9, POSTN, and CA242, to discriminate early stage PDAC not only from healthy controls (area under the curve [AUC]_CA19.9 = 0.94 vs AUC_{CA19.9 + POSTN + CA242} = 0.98, P < .05) but also from benign conditions (AUC_CA19.9 = 0.87 vs AUC_{CA19.9 + POSTN + CA242} = 0.90, P < .05). In addition, POSTN retained significant diagnostic capabilities to distinguish PDAC CA19.9‐negative from healthy controls (AUC_POSTN = 0.87) as well as from benign conditions (AUC_POSTN = 0.84) in the whole set. This study suggested that POSTN and CA242 are potential diagnostic serum biomarkers complementing CA19.9 in detecting early pancreatic cancer.

Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis.

Background: Breast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction. Methods: To assess the potential of soluble POSTN as a circulating biomarker, 242 participants, including 173 patients with different stages of BCa and 69 healthy individuals, were enrolled in this study. Soluble POSTN, together with CA153 and CEA, were determined in serum by enzyme linked immunosorbent assay (ELISA) or electrochemiluminescence immunoassays. Results: Serum POSTN levels in locoregional BCa patients were significantly higher than that in healthy controls. Receiver operating curve (ROC) analysis revealed that, to distinguish health controls from locoregional BCa, POSTN was observed with the highest AUC (area under curve) (AUC_POSTN = 0.72 [0.65 – 0.79], AUC_CA153 = 0.57 [0.49 – 0.64], AUC_CEA = 0.62 [0.55 – 0.69]), and both CA153 and CEA were observed with significantly improved AUCs by combination with POSTN (AUC_{POSTN + CA153} = 0.74 [0.67 – 0.80], P < 0.001; AUC_{POSTN + CEA} = 0.77 [0.70 – 0.82], P < 0.001). Moreover, the performances of the POSTN were comparable with that of CA153 in predicting distant metastasis of BCa (AUC_POSTN = 0.78 [0.71 – 0.84], AUC_CA153 = 0.82 [0.76 – 0.88]). Kaplan–Meier analysis indicated that elevated serum POSTN was associated with poor overall survival and progression-free survival. Conclusions: This study suggested that soluble POSTN is a promising potential biomarker for diagnosis and metastasis prediction of BCa.

Objective Mitochondria play multifunctional roles in carcinogenesis. Deciphering uncertainties of molecular interactions within mitochondria will promote further understanding of cancer. Interleukin enhancer binding factor 2 (ILF2) is upregulated in several malignancies, however, much remains unknown regarding ILF2 in small cell lung cancer (SCLC). In the current study, we explored ILF2’s role in SCLC and demonstrated its importance in mitochondria quality control. Methods Colony formation, cell proliferation, cell viability and xenograft studies were performed to examine ILF2’s role on SCLC progression. Glucose uptake, lactate production, cellular oxygen consumption rate and extracellular acidification rate were measured to examine the effect of ILF2 on glucose metabolism. RNA-sequencing was utilized to explore genes regulated by ILF2. E2F1 transcriptional activity was determined by dual luciferase reporter assay. Mitochondria quantification and mitochondrial membrane potential assays were performed to examine mitochondrial quality. Gene expression was determined by RT-qPCR, Western blot and IHC assay. Results ILF2 promotes SCLC tumor growth in vitro and in vivo. ILF2 elevates oxidative phosphorylation expression and declines glucose intake and lactate production. Genome-wide analysis of ILF2 targets identified a cohort of genes regulated by E2F1. In consistent with this, we found ILF2 interacts with E2F1 in SCLC cells. Further studies demonstrated that suppression of E2F1 expression could reverse ILF2-induced tumor growth and enhanced mitochondria function. Significantly, expression of ILF2 is progressively increased during SCLC progression and high ILF2 expression is correlated with higher histologic grades, which indicates ILF2’s oncogenic role in SCLC. Conclusions Our results demonstrate that ILF2 interacts with E2F1 to maintain mitochondria quality and confers SCLC cells growth advantage in tumorigenesis.