Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

S. D’Angelo, M. Mahoney, B. V. Van Tine et al.

Rodolfo L. Chávez-Domínguez, Martha Torres, Atziri A. Acevedo-Domínguez et al.

Pulmonary tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of infectious disease-related mortality worldwide. In parallel, lung cancer represents the most lethal neoplasm, with high mortality rates globally. Emerging studies suggest that chronic Mtb infection may contribute to the development of lung cancer, particularly adenocarcinoma. Several biological mechanisms support this hypothesis. Chronic inflammation from tuberculosis creates a microenvironment enriched in proinflammatory cytokines, reactive oxygen species (ROS), and growth factors that favor cell proliferation, genomic instability, angiogenesis, and immune evasion, which are considered classic hallmarks of cancer. Additionally, both protein and non-protein virulence factors of Mtb have been shown to interfere with critical cellular signaling pathways related to tumor cell survival and invasion. Clinically, multiple observational studies and meta-analyses report an increased incidence of lung cancer among individuals with a history of tuberculosis, especially when both conditions coexist in the same pulmonary regions. Specific mutations, including EGFR, have been identified in patients with prior tuberculosis, influencing both prognosis and therapeutic response. Nevertheless, key questions remain regarding the causal nature of this association, the role of Mtb strains, and the molecular factors such as epigenetic modifications or the lung microbiome. This review proposes that infection with Mtb could function as a carcinogenic agent. Further in vitro experiments, cellular models, and clinical investigations are urgently needed to support potential reclassification of this pathogen by international agencies such as the IARC.

Legang Huang, Zijie Wang, Jiankuan Lu

This report presents the case of a 68-year-old female patient with hepatocellular carcinoma (HCC) who experienced persistently elevated alpha-fetoprotein (AFP) levels following resection of the primary liver tumor. The patient had previously undergone transcatheter arterial chemoembolization (TACE) and liver tumor resection, but postoperative AFP levels continued to rise, suggesting the possibility of extrahepatic metastasis. PET-CT scans revealed an irregular soft tissue mass in the recto-uterine pouch, which was later confirmed as a HCC metastasis through needle biopsy. The patient subsequently received radioactive seed implantation therapy, leading to a significant decrease in AFP levels. This case highlights the rarity of isolated pelvic metastasis in HCC patients and underscores the importance of AFP in postoperative monitoring. The combination of PET-CT imaging and pathological biopsy is instrumental in improving the detection rate of HCC metastases, enabling more accurate treatment planning for patients.

Mi‐Hyun Kim, Min Ki Lee, Ji Eun Park et al.

ABSTRACT Introduction The clinical application of lazertinib, a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has extended to the treatment of EGFR‐mutant non‐small‐cell lung cancer (NSCLC); however, the effects of its dose modification on its efficacy and safety have not yet been adequately established. Methods This prospective, multicenter, observational cohort study aims to evaluate the clinical implications of adjusting the lazertinib dose. Patients will be categorized into two groups based on the lazertinib dose administered during the initial 12 weeks of treatment in routine clinical practice: 160 and 240 mg groups. The primary endpoints are progression‐free survival in the 160 mg group and identifying risk factors associated with dose modification during the 12‐week period. Discussion The findings from the present study will provide real‐world insights into the clinical factors leading to lazertinib dose adjustments and deepen our understanding of the efficacy and safety of lazertinib in patients with NSCLC. Our research will contribute toward optimizing medical strategies for NSCLC treatment and aid clinicians in making accurate clinical decisions regarding dose modifications in routine practice.

Archna Dhasmana, Ayushi Santhanam, Khushi Dhasmana et al.

Cancer is still a major health concern worldwide, requiring ongoing improvements in methods of diagnosis and treatment. During the past decade, smart biosensors have become essential instruments in cancer theranostics, improving diagnosis accuracy, tracking treatment efficacy, and customizing patient care. This review thoroughly investigates how smart biosensors have revolutionized the field of cancer. The potential of major technical advancements, such as wearable technology, microfluidic platforms, and sensors based on nanomaterials to identify cancer biomarkers with high sensitivity and specificity is investigated. A detailed discussion is held regarding clinical applications that include early diagnosis, real-time monitoring of therapy responses, and support for personalized medicine techniques. Future directions targeted at optimizing the therapeutic utility of smart biosensors in oncology are also examined, along with issues pertaining to regulatory routes and clinical translation hurdles. This study highlights the potential of smart biosensors to transform cancer treatment, bringing in a new era of precision medicine and better patient outcomes by combining insights from multiple viewpoints.

Ruidong Xue, Jinghui Cheng, Ning Zhang

Frontiers Editorial Office

Xianzhe Fan, Ran Zhong, Hengrui Liang et al.

Abstract Background Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection remains crucial for improving patient outcomes. The accuracy of screening for LC by detecting volatile organic compounds (VOCs) in exhaled breath remains to be determined. Methods Our systematic review, following PRISMA guidelines and analyzing data from 25 studies up to October 1, 2023, evaluates the effectiveness of different techniques in detecting VOCs. We registered the review protocol with PROSPERO and performed a systematic search in PubMed, EMBASE and Web of Science. Reviewers screened the studies’ titles/abstracts and full texts, and used QUADAS-2 tool for quality assessment. Then performed meta-analysis by adopting a bivariate model for sensitivity and specificity. Results This study explores the potential of VOCs in exhaled breath as biomarkers for LC screening, offering a non-invasive alternative to traditional methods. In all studies, exhaled VOCs discriminated LC from controls. The meta-analysis indicates an integrated sensitivity and specificity of 85% and 86%, respectively, with an AUC of 0.93 for VOC detection. We also conducted a systematic analysis of the source of the substance with the highest frequency of occurrence in the tested compounds. Despite the promising results, variability in study quality and methodological challenges highlight the need for further research. Conclusion This review emphasizes the potential of VOC analysis as a cost-effective, non-invasive screening tool for early LC detection, which could significantly improve patient management and survival rates.

Guillaume Mestrallet

Strategies for tackling cancer involve surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors (ICB). However, the effectiveness of ICB remains constrained, prompting the need for a proactive strategy to foresee treatment responses and resistances. This study undertook an analysis across diverse cancer patient cohorts (including melanoma, clear cell renal carcinoma, glioblastoma, bladder, and stomach cancers) subjected to various immune checkpoint blockade treatments. Surprisingly, our findings unveiled that over 38% of patients demonstrated resistance and persistent disease progression despite undergoing ICB intervention. To unravel the intricacies of resistance, we scrutinized the immune profiles of cancer patients experiencing ongoing disease progression and resistance post-ICB therapy. These profiles delineated multifaceted defects, including compromised macrophage, monocyte, and T cell responses, impaired antigen presentation, aberrant regulatory T cell (Tregs) responses, and an elevated expression of immunosuppressive and G protein-coupled receptor molecules (TGFB1, IL2RA, IL1B, EDNRB, ADORA2A, SELP, and CD276). Building upon these insights into resistance profiles, we harnessed machine learning algorithms to construct models predicting the response and resistance to ICB and developed the accompanying software. While previous work on glioblastoma with only one type of algorithm had an accuracy of 0.82, we managed to develop 20 models that provided estimates of future events of resistance or response in five cancer types, with accuracies ranging between 0.79 and 1, based on their distinct immune characteristics. In conclusion, our approach advocates for the personalized application of immunotherapy in cancer patients based on patient-specific attributes and computational models.

Enrique Soto-Pérez-de-Celis

Please the the content in english.

Fang-Shu Ou, Emil Lou, Joanne Xiu et al.

Background The C-C motif chemokine receptor 5 (CCR5)/C-C motif chemokine ligand 5 (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with CCR5/CCL5 expression in CRC and to determine whether CCR5/CCL5 levels could impact treatment outcomes.Methods 7604 CRCs tested with NextGen Sequencing on DNA and RNA were analyzed. Molecular features were evaluated according to CCR5 and CCL5 tumor gene expression quartiles. The impact on treatment outcomes was assessed in two cohorts, including 6341 real-world patients and 429 patients from the Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial.Results CCR5/CCL5 expression was higher in right-sided versus left-sided tumors, and positively associated with consensus molecular subtypes 1 and 4. Higher CCR5/CCL5 expression was associated with higher tumor mutational burden, deficiency in mismatch repair and programmed cell death ligand 1 (PD-L1) levels. Additionally, high CCR5/CCL5 were associated with higher immune cell infiltration in the tumor microenvironment (TME) of MMR proficient tumors. Ingenuity pathway analysis revealed upregulation of the programmed cell death protein 1 (PD-1)/PD-L1 cancer immunotherapy pathway, phosphatase and tensin homolog (PTEN) and peroxisome proliferator-activated receptors (PPAR) signaling, and cytotoxic T-lymphocyte antigen 4 (CTLA-4) signaling in cytotoxic T lymphocytes, whereas several inflammation-related pathways were downregulated. Low CCR5/CCL5 expression was associated with increased benefit from cetuximab-FOLFOX treatment in the CALGB/SWOG 80405 trial, where significant treatment interaction was observed with biologic agents and chemotherapy backbone.Conclusions Our data show a strong association between CCR5/CCL5 gene expression and distinct molecular features, gene expression profiles, TME cell infiltration, and treatment benefit in CRC. Targeting the CCR5/CCL5 axis may have clinical applications in selected CRC subgroups and may play a key role in developing and deploying strategies to modulate the immune TME for CRC treatment.

Farhad Jeddi, Elnaz Faghfuri, Sahar Mehranfar et al.

Abstract DNA methylation is an important molecular modification that plays a key role in the expression of cancer genes. Evaluation of epigenetic changes, hypomethylation and hypermethylation, in specific genes are applied for cancer diagnosis. Numerous studies have concentrated on describing DNA methylation patterns as biomarkers for cancer diagnosis monitoring and predicting response to cancer therapy. Various techniques for detecting DNA methylation status in cancers are based on sodium bisulfite treatment. According to the application of these methods in research and clinical studies, they have a number of advantages and disadvantages. The current review highlights sodium bisulfite treatment-based techniques, as well as, the advantages, drawbacks, and applications of these methods in the evaluation of human cancers.

Emad Ababneh, W. Faquin

Cancers of the sinonasal tract represent a broad, heterogeneous group of tumors that can present significant diagnostic challenges for the surgical pathologist as well as management issues for the treating otolaryngology clinician. Greater than 60% of sinonasal malignancies are squamous cell carcinomas, and patients have an average 5‐year overall survival rate of 50%. Sinonasal adenocarcinoma and olfactory neuroblastoma are among the cancers with the best prognosis, with 67% and 62% 5‐year overall survival rates, respectively. The fifth edition of the World Health Organization Classification of Head and Neck Tumours (2022) recognizes at least 10 types of primary sinonasal cancer (Table 1) in addition to other infrequent malignant neoplasms not specific to the sinonasal cavity, such as rhabdomyosarcoma, Ewing sarcoma, and diffuse large B‐cell lymphoma among others. In some cases, such as olfactory neuroblastoma, sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma, and mucosal melanoma, sinonasal cancers will metastasize to regional lymph nodes or to distant sites, where they may be sampled by fine‐needle aspiration (FNA). The cytologic evaluation and diagnosis of this rare heterogeneous group of malignancies can be challenging, and a general familiarity by cytologists and practicing pathologists with the spectrum of sinonasal malignancies and their management is useful. In this commentary, we review the recent article by Thawani et al., which summarizes the current management approaches to the most common sinonasal malignancies. The recent report by Thawani et al. highlights updates in the molecular profiles, prognosis, and clinical management of selected sinonasal malignancies, focusing on cancers specific to the sinonasal tract as well as some occurring in the head and neck and often involving the sinonasal tract. Thawani et al. expand upon the available approaches to management for sinonasal cancers compared with the current National Comprehensive Cancer Network guidelines. A shared feature between the two management approaches is the use of fewer treatment branch points compared with corresponding tumor types, as published in the fifth edition of the World Health Organization Classification of Tumours of the Head and Neck. For example, the sections on sinonasal squamous cell carcinoma and sinonasal adenocarcinoma do not distinguish between keratinizing and nonkeratinizing types (or between human papillomavirus‐ associated and human papillomavirus‐independent types) for the former or between intestinal and nonintestinal types for the latter, although there are differences in the histopathologic features and/or prognosis for these sinonasal cancers. In addition, SWI/SNF‐complex–deficient carcinomas (including SMARCB1‐deficient sinonasal carcinomas) are included briefly when discussing the highly aggressive SNUC. This reflects data that the authors present from currently available treatment options and clinical trials. It is not surprising that the management approaches for the most common sinonasal cancers as presented by Thawani et al. contrast with the more granular diagnostic approach used by pathologists, which includes not only the more common cancer types but also rare tumor subtypes. In this regard, the role of pathology in continually analyzing and refining tumor classification is extremely important for advancing the field of oncology and, most importantly, for driving advances in patient care. The pathology literature includes many reports about the morphologic and biologic subtypes of sinonasal cancers with the intent of ensuring appropriate classification and prognostication as well as the possibility that such classification will have either present or future implications for management. In this way, clinical management algorithms often lag behind the ability of pathologists to subtype cancers, and this is especially true for rare cancers. One example to address this would be the recent ongoing shift toward the so‐called basket or umbrella clinical trials. Such a framework offers advantages, including the ability to advance treatment for some rare tumors that would otherwise be difficult to study on their own. They recruit and group tumors with a shared driver molecular alteration in a tumor type‐agnostic way. This is particularly relevant for the growing number of sinonasal cancer subtypes with specific genetic alterations, such as IDH2‐mutant SNUCs and SWI/ SNF‐deficient tumors, among others. Multiple clinical trials are now in

Wang S, Zhang X, Chen Q et al.

Shangyuan Wang, Xuanpu Zhang, Qi Chen, Zhi-Cheng Jin, Jian Lu, Jinhe Guo Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Jian Lu; Jinhe Guo, Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Tel +86-25-83262230 ; +86-25-83272121, Email lujian43307131@126.com; jinheguo@sina.comPurpose: Transarterial chemoembolization (TACE) was commonly applied in hepatocellular carcinoma (HCC) patients across BCLC A-C stages with heterogeneous outcomes in real-world practice. We aimed to develop a neutrophil-to-lymphocyte ratio (NLR) and sarcopenia-based prognostic nomogram to estimate the prognosis of HCC patients after TACE treatment.Patients and Methods: Between June 2013 and December 2019, a total of 364 HCC patients who underwent TACE were included and randomly assigned to the training (n=255) and the validation cohort (n=109). Sarcopenia was diagnosed based on the third lumbar vertebra skeletal muscle mass index (L3-SMI). The multivariate Cox proportional risk model was used to generate a nomogram.Results: NLR ≥ 4.0, sarcopenia, alpha-fetoprotein (AFP) ≥ 200 ng/mL, albumin-bilirubin (ALBI) grade 2 or 3, number of lesions (≥ 2), and maximum size of the lesion (≥ 5 cm) were independent predictors for overall survival (OS) (P < 0.05). The calibration curve shows that the predicted results agree well with the observed results. The time-dependent areas under the receiver-operating characteristic curves for OS at 1, 2, and 3 years predicted by the nomogram were 0.818/0.827, 0.742/0.823, and 0.748/0.836 in both training and validation cohorts. Nomogram can divide patients into low-, medium- and high-risk groups based on predictor factors. The C-indexes of the nomogram for OS were 0.782/0.728 in the training and validation cohorts, outperforming other currently available models.Conclusion: A novel nomogram based on NLR and sarcopenia may be useful to predict the prognosis of HCC patients who underwent TACE across BCLC A-C stage patients.Keywords: hepatocellular carcinoma, transarterial chemoembolization, neutrophil-to-lymphocyte ratio, sarcopenia, albumin-bilirubin, nomogram

L. Klyukina, E. Sosnova, A. Ishchenko et al.

BACKGROUND: Primary multiplicity of malignant tumors of the female reproductive system is the least studied area of clinical oncology. In addition, the steady rise in the number of patients and various localizations of polyneoplasia with lesions of the female reproductive organs necessitate a detailed study of this problem. AIM: This study aimed to determine the incidence and risk factors and describe the clinical aspects of polyneoplasia of the female reproductive system for 20102021 in women seen at the Medical and Rehabilitation Center of the Ministry of Health of Russia, Moscow, and the University Clinical Hospital No. 4 of the I.M. Sechenov First Moscow State Medical University. MATERIALS AND METHODS: We conducted a retrospective analysis of the case records of 147 patients with a confirmed diagnosis of polyneoplasia of the female reproductive system for 20102021, which accounted for 3.6% of all newly diagnosed neoplasms of the female reproductive system in the above medical institutions. Moreover, a continuous sampling method was used. RESULTS: Breast cancer was the most frequent first tumor, combined with cancer of the contralateral breast in 27 (42.1%) patients, cancer of the uterine body in 4 (6.25%) patients, ovarian cancer in 4 (6.25%) patients, colon cancer in 4 (6.25%) patients, and thyroid cancer in 1 (1.5%) patient. Cancer of the uterine body was combined with breast cancer in 10 (35.7%) patients, ovarian cancer in 2 (7.1%) patients, thyroid cancer in 2 (7.1%) patients, and colon cancer in 3 (11.1%) patients. Endometrioid adenocarcinoma, pathogenic variant I was determined in 20 (71.4%) cases according to the histological structure. Thyroid cancer was detected in 7 (5.6%) cases; in all cases, it developed metachronously, and it was combined as the initial tumor with breast cancer in 1 (14.3%) case, uterine body cancer in 2 (28.5%) cases, and ovarian cancer in 1 (14.3%) case. As the second tumor, it was also combined with uterine body cancer in 2 (28.5%) cases and ovarian cancer in 1 (14.3%) case. The risk factors assessment led to the identification of several factors that are common in patients with hormone-dependent forms of primary multiple cancer, including obesity, diabetes mellitus, irregular menstrual cycle, history of proliferative diseases of the mammary glands, intake of thyroid drugs, uterine hyperplastic processes, and hypothyroidism. CONCLUSIONS: Understanding the different aspects of the development and course of hormone-dependent polyneoplasia of the female reproductive system will help in developing approaches for follow-up monitoring of women who have been treated for a primary tumor and are at risk of developing a subsequent tumor of hormone-dependent organs, to prevent the recurrence of the disease and predict the subsequent tumor and ensure its timely detection.

Huo S, Dou D

Shousong Huo,1 Dongmei Dou2 1Department of Orthopaedic, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, People&rsquo;s Republic of China; 2Institute of Chronic Disease Risk Assessment, Henan University, Jinming Campus, Kaifeng, 475000, Henan, People&rsquo;s Republic of ChinaCorrespondence: Dongmei DouInstitute of Chronic Disease Risk Assessment, Henan University, Jinming Campus, Kaifeng, 475000, Henan, People&rsquo;s Republic of ChinaTel +86-0371-23885066Email doudongmei@henu.edu.cnBackground: Osteosarcoma (OS) is a common malignant bone cancer that occurs in adolescents and children. Circular RNAs (circRNAs) are important regulators of tumorigenesis and development. This study aimed to explore the role and molecular basis of circ_0056285 in OS.Methods: The levels of circ_0056285, miR-1244 and tripartite motif containing 44 (TRIM44) were determined by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell apoptosis was assessed by flow cytometry and caspase 3and caspase 9 activity assay kits. Glucose uptake, lactate product and ATP level were examined using commercial kits. Hexokinase II (HK2) and lactate dehydrogenase A (LDHA) levels were measured by Western blot assay. The interaction among circ_0056285, miR-1244 and TRIM44 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. Xenograft experiment was conducted to explore tumor growth in vivo. Exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western blot. The diagnostic value of exosomal circ_0056285 was evaluated by receiver operating characteristic (ROC) curve.Results: Circ_0056285 and TRIM44 were up-regulated, and miR-1244 was down-regulated in OS tissues and cells. Circ_0056285 silencing inhibited proliferation and glycolysis and promoted apoptosis in OS cells. Also, circ_0056285 knockdown hindered proliferation and accelerated apoptosis in OS cells by regulating miR-1244/TRIM44 axis. Circ_0056285 depletion impeded tumor growth in vivo. Furthermore, ROC curve showed that circ_0056285 might be a diagnostic biomarker in OS.Conclusion: Circ_0056285 facilitated OS progression by sponging miR-1244 and increasing TRIM44 expression, providing a promising therapeutic target for OS.Keywords: osteosarcoma, circ_0056285, miR-1244, TRIM44, progression

Shuyan Yao, Zhili Jin, Lingbo He et al.

BackgroundMalignancies, especially lymphoma, are a common cause of adult secondary HLH and an independent risk factor for the prognosis of HLH patients.MethodsPatients with lymphoma alone or concurrent lymphoma-associated phagocytic syndrome (LAHS) admitted to Beijing Friendship Hospital from January 2016 to December 2020 were enrolled in this study.FindingsThere were 348 lymphoma patients, 104 concurrent with LAHS. The pathological type of lymphoma without LAHS was dominated by B-cell lymphoma, while those with LAHS were T/NK-cell lymphoma predominantly (p &lt; 0.001). Superficial lymph node enlargement was more significant in patients with B-LAHS (p = 0.006), while patients with T/NK-LAHS had lower neutrophil counts (p = 0.005), lower fibrinogen levels (p &lt; 0.001), higher transaminase levels, and more co-infection with EBV (p &lt; 0.001). B-LAHS had significantly higher IL-10 levels than with T/NK-LAHS (p = 0.006), and NK/T-LAHS had significantly higher IP-10 levels than other T-LAHS (p = 0.008). Age, platelet count, IPI, history of NK/T lymphoma, and no remission of HLH were independent risk factors for prognosis in patients with non-Hodgkin lymphoma-associated phagocytic syndrome (NHL-LAHS), and a prognostic risk score model for NHL-LAHS was developed.ConclusionLAHS is a life-threatening disease with a poor prognosis. The prognostic risk score model for NHL-LAHS with a good fit and validation for the test has value for clinical application.

Aref Shariati, Shabnam Razavi, Ehsanollah Ghaznavi-Rad et al.

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

Tadashi Sakane, Y. Sakamoto, A. Masaki et al.

BACKGROUND Thymic carcinoma is a rare mediastinal neoplasm, and little is known about its genetic variability, which has hampered the development of targeted therapies. PATIENTS AND METHODS We tested a next-generation sequencing panel containing 50 common cancer-related genes in 48 cases of thymic carcinoma and 6 cases of thymic neuroendocrine tumor. RESULTS We detected 42 variant calls in 21 of 54 cases. There was no significant difference in mutation frequency between thymic carcinoma and thymic neuroendocrine tumors. Among these, TP53 was the most frequently mutated gene (18.5%), followed by KIT (7.4%) and PDGFRA (5.6%). According to the gene pathways and groups, the p53 pathway, including TP53 and ATM, was most frequently affected (20.4%), followed by the receptor tyrosine kinase (RTK)/RAS pathway (18.5%) and PI3K pathway (5.6%). According to the OncoKB, an expert-guided precision oncology knowledge base, 7 genes among 10 cases (18.5%) were annotated with level 1 evidence, suggesting potentially therapeutic targets. Prognostic analyses, conducted in thymic squamous cell carcinomas, revealed that tumor cases harboring gene mutations in RTKs, including KIT (7.4%), PDGFRA (5.6%) and EGFR (3.7%), were significantly associated with a worse overall survival time (P = .0481). Among clinicopathologic factors, the advanced Masaoka stage was marginally associated with a worse overall survival (P = .0757). In the subsequent multivariate analysis, neither of the factors achieved statistical significance. CONCLUSIONS In this preliminary next-generation sequencing study, we unexpectedly found evidence suggesting that several gene mutations might be therapeutic targets. The gene mutations in RTKs may be a valuable prognostic factor in thymic squamous cell carcinoma.

T. Kawasaki, K. Kaira