Identification of Circular RNAs as Biomarker Candidates in Lung Cancer Treatment.

OBJECTIVE: Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Therefore, there is an important need for biomarkers that can be used in the early diagnosis of the disease and in the follow-up of treatment. Circular RNAs (circRNAs) have a covalently closed circular structure that lacks 3' and 5' polar ends and is resistant to RNAase enzymes. Due to these properties, they can be stably found in body fluids. Therefore, they can serve as potential biomarkers in the diagnosis, monitoring of therapeutic response and prognosis of cancer. In our study, we aimed to investigate the expression levels of circRNA molecules in the treatment of lung cancer and to determine those that have the potential to be biomarkers. METHODS: In this in vitro study, expression levels of 163 circRNAs were investigated in A549 cells, a non-small cell lung cancer cell line, before and after treatment with carboplatin and pemetrexed. Total RNA isolation and cDNA synthesis were performed after treatments. Expression levels of circRNA genes were determined by RT-qPCR method with the designed divergent primer sequences. RESULTS: The study revealed the characterisation of differentially expressed circRNAs by treatment in lung cancer cells. Of them, hsa_circ_0001320 is not expressed in cancer cells, is expressed only after treatment, and increased the level of its expression in response to combination therapy. CONCLUSION: As a result, while carboplatin, pemetrexed, and combined drug applications changed the expression levels of some circRNAs in lung cancer cells, some circRNAs were expressed only after treatment. In treatment follow-up and management, hsa_circ_0001320 has been identified as potential biomarker candidate.

Salivary Lipids of Patients with Non-Small Cell Lung Cancer Show Perturbation with Respect to Plasma.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. This study investigated 297 and 202 lipids in saliva and plasma samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (>2-fold, p < 0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes. Total triglycerides (TGs) increased (>2-3-fold) in plasma and saliva samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC for both sample types. A common ceramide species (d18:1/24:0) and phosphatidylinositol 38:4 decreased in both plasma and saliva by approximately two-fold. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. We identified 27 salivary and 10 plasma lipids as candidate markers for NSCLC through statistical evaluations. Moreover, this study highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

Profiling of circRNA expressions in radiation-treated head and neck cancer cells and the potential role of circPVT1.

OBJECTIVE: Radiotherapy is an indispensable treatment modality for head and neck cancers (HNCs). Due to their stable structure, circular RNAs (circRNA) have been implicated as potential biomarkers for clinical use in cancers. The purpose of this study was profiling the circRNA in radiation-treated head and neck cancer cells to identify potential differentially expressed circRNAs. DESIGN: The effects of radiation on the expression level of circRNAs were investigated in HNCs cells, compared to healthy cell lines. To predict the potential role of circRNAs in HNC patients, tissue expression levels, survival analyses of circRNAs, and circRNA-miRNA network were evaluated using TCGA/CPTAC datasets. Based on expression level in irradiated cells, circPVT1 (plasmacytoma variant translocation 1) was further investigated by sequence analysis. RESULTS: The study revealed the characterization of differentially expressed circRNAs in cancer cells and that irradiation made significant changes in the expression of circRNAs. These findings suggest that certain circRNAs, especially circPVT1, may be potential biomarkers to monitor radiotherapy effects in patients with HNCs. CONCLUSIONS: CircRNAs may be promising molecules for improving and understanding radiotherapy efficacy in HNCs.

Molecular Prevalence of Microsporidia Infection in Patients with Lung Cancer.

Infections are still among the most important causes of morbidity and mortality in patients with lung cancer, which has the highest rate of cancer-related deaths in the world. Microsporidia, which are opportunistic parasitic fungi, primarily localize to the intestine by ingestion but can disseminate to the respiratory tract or can be acquired by spore inhalation. Cancer patients are at higher risk for microsporidia, a life-threatening infection, than the normal population is. We aimed to characterize the prevalence of microsporidia infection for the first time by evaluating the intestinal and respiratory tracts of patients with lung cancer. In this study, we investigated 98 patients with lung cancer and 103 healthy individuals for microsporidia infection and evaluated the clinical findings of patients who were found to be positive. Sputum and stool samples were tested by microscopic examination, in addition to pan-microsporidia and genus-specific polymerase chain reactions. Nine patients with lung cancer had positive results for microsporidia (9.2%), which was significantly higher than the rate in healthy individuals (P = 0.008), and most of them had clinical findings. Among these positive patients, polymerase chain reaction revealed microsporidia in the sputum samples of seven patients, the stool sample of one patient, and both the sputum and stool samples of one patient. Encephalitozoon cuniculi was identified as the predominant pathogen in 87.5% (7/8) of positive sputum samples. Microsporidia infection was significantly associated with advanced stages of cancer. However, in the control group, Encephalitozoon intestinalis was detected in the stool sample of an individual without clinical symptoms. Microsporidia, especially E. cuniculi, should be considered as a cause of respiratory tract infection as well as intestinal infection in cancer patients and should be screened in respiratory samples of these patients when they have pulmonary symptoms.

Detection of Pneumocystis jirovecii by PCR in patients with lung cancer: A preliminary study.

INTRODUCTION: Infection complications in lung cancer (LC), one of the most common cancers in the world, are still among the most important causes of death. Of them, P. jirovecii, which is as an opportunistic infection, causes a life-threatening type of pneumonia in cancer patients. This preliminary study aimed to determine the incidence and clinical status of P. jirovecii by PCR in lung cancer patients compared to the conventional method. MATERIAL AND METHODS: Sixty-nine lung cancer patients and fSorty healthy individuals were included in the study. After sociodemographical and clinical features were recorded, sputum samples were collected from attenders. Firstly, microscopic examination was made with Gomori's methenamine silver stain and then PCR was performed. RESULTS: P. jirovecii was detected in three of 69 lung cancer patients by PCR (4.3%), but not by microscopy. However, healthy individuals were negative for P. jirovecii by both methods. Based on clinical and radiological findings, P. jirovecii was evaluated as probable infection in one patient and colonization in the other two patients. Although PCR is more sensitive than conventional staining methods, it cannot distinguish probable and proven infections from pulmonary colonization. DISCUSSION: It is important to evaluate the decision of infection together with laboratory, clinical and radiological findings. Moreover, PCR may enable to know the colonization and to take precautions such as prophylaxis, due to the risk of colonization turning into an infection in immunocompromised patient groups. Further studies involving larger populations and evaluating the colonization-infection relationship in patients with solid tumors are needed.

The Effect of BTK Inhibitor Ibrutinib on Leishmania infantum Infection In Vitro.

PURPOSE: Leishmaniasis is a neglected infectious disease affecting millions of people worldwide. Visceral leishmaniasis (VL), caused by Leishmania infantum and Leishmania donovani, is one of the main clinical forms of the disease and fatal if not treated promptly and properly. Despite being available for the last 70 years, current drugs used in the treatment of leishmaniasis have serious problems as they have high toxicity, require long-term administration and cause serious side-effects, leading to the emergence of resistant and relapse cases. Therefore, there is an urgent need for the discovery of novel antileishmanial molecules and the development of new treatment regimens. The drug used for chemotherapy of B-cell malignancies, Ibrutinib, an inhibitor of Bruton's Tyrosine Kinase (BTK), can offer a new therapeutic perspective due to the functions of BTK on intracellular signaling mechanism of macrophages, which are the primary resident cell for Leishmania. Hence, the study aimed to evaluate ibrutinib as a potential anti-Leishmanial drug. METHOD: In this study, we evaluated the antileishmanial effect of Ibrutinib by in vitro L. infantum infection model using macrophages, with cell viability assay, parasite rescue assay, real-time qPCR. RESULTS: We showed that Ibrutinib was significantly more effective than the Glucantime against L. infantum. In addition, our data revealed that Ibrutinib inhibited parasite growth and load without impairing macrophage viability. CONCLUSIONS: Consequently, due to its efficacy and safety, Ibrutinib may be a promising candidate for the treatment of VL caused by L. infantum as a host-targeted drug.

A Pilot Study on the Evaluation of Cryptosporidium Infection in Patients with Lung Cancer: Respiratory Cryptosporidiosis.

Lung carcinoma is one of the most common cancers and the leading cause of cancer-related death worldwide. Increasing evidence has shown that Cryptosporidium spp., an opportunistic parasite, is associated with cancers, causing life-threatening infections. The most common clinical form of Cryptosporidium is intestinal infections. However, respiratory cryptosporidiosis has rarely been documented, although the parasite infects respiratory epithelial cells and gastrointestinal (GIS) epithelial cells. To evaluate respiratory cryptosporidiosis in patients with lung cancer, we investigated Cryptosporidium spp. in patients with lung cancer (n = 69) in comparison with healthy groups (n = 40). Sputum and stool samples were examined microscopically and by polymerase chain reaction (PCR). Two cancer patients were diagnosed with respiratory cryptosporidiosis (2.9%), on PCR examination of the sputum samples. Cryptosporidium spp. was detected in the stool samples of one patient (1.5%) and 2 healthy individuals (5.4%) by PCR and microscopy. First, respiratory cryptosporidiosis was documented in 2 patients with lung cancer. Cryptosporidium is an important agent of the respiratory tract and GIS infections in cancer patients. These new findings highlight the molecular prevalence of Cryptosporidium spp., an opportunistic infection, in patients with lung cancer. Respiratory cryptosporidiosis should also be considered when patients have respiratory symptoms.