Purpose This study aimed to investigate the dynamic changes in the microbiome of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT), focusing on the relationship between the microbiome and response to nCRT.
Materials and Methods We conducted a longitudinal study involving 103 samples from 26 patients with LARC. Samples were collected from both the tumor and normal rectal tissues before and after nCRT. Diversity, taxonomic, and network analyses were performed to compare the microbiome profiles across different tissue types, pre- and post-nCRT time-points, and nCRT responses.
Results Between the tumor and normal tissue samples, no differences in microbial diversity and composition were observed. However, when pre- and post-nCRT samples were compared, there was a significant decrease in diversity, along with notable changes in composition. Non-responders exhibited more extensive changes in their microbiome composition during nCRT, characterized by an increase in pathogenic microbes. Meanwhile, responders had relatively stable microbiome communities with more enriched butyrate-producing bacteria. Network analysis revealed distinct patterns of microbial interactions between responders and non-responders, where butyrate-producing bacteria formed strong networks in responders, while opportunistic pathogens formed strong networks in non-responders. A Bayesian network model for predicting the nCRT response was established, with butyrate-producing bacteria playing a major predictive role.
Conclusion Our study demonstrated a significant association between the microbiome and nCRT response in LARC patients, leading to the development of a microbiome-based response-prediction model. These findings suggest potential applications of microbiome signatures for predicting and optimizing nCRT treatment in LARC patients.
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Purpose This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.
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Young-Gon Kim, In Hye Song, Hyunna Lee, Sungchul Kim, Dong Hyun Yang, Namkug Kim, Dongho Shin, Yeonsoo Yoo, Kyowoon Lee, Dahye Kim, Hwejin Jung, Hyunbin Cho, Hyungyu Lee, Taeu Kim, Jong Hyun Choi, Changwon Seo, Seong il Han, Young Je Lee, Young Seo Lee, Hyung-Ryun Yoo, Yongju Lee, Jeong Hwan Park, Sohee Oh, Gyungyub Gong
Cancer Res Treat. 2020;52(4):1103-1111. Published online June 30, 2020
Purpose
Assessing the status of metastasis in sentinel lymph nodes (SLNs) by pathologists is an essential task for the accurate staging of breast cancer. However, histopathological evaluation of sentinel lymph nodes by a pathologist is not easy and is a tedious and time-consuming task. The purpose of this study is to review a challenge competition (HeLP 2018) to develop automated solutions for the classification of metastases in hematoxylin and eosin–stained frozen tissue sections of SLNs in breast cancer patients.
Materials and Methods
A total of 297 digital slides were obtained from frozen SLN sections, which include post–neoadjuvant cases (n = 144, 48.5%) in Asan Medical Center, South Korea. The slides were divided into training, development, and validation sets. All of the imaging datasets have been manually segmented by expert pathologists. A total of 10 participants were allowed to use the Kakao challenge platform for six weeks with two P40 GPUs. The algorithms were assessed in terms of the AUC (area under receiver operating characteristic curve).
Results
The top three teams showed 0.986, 0.985, and 0.945 AUCs for the development set and 0.805, 0.776, and 0.765 AUCs for the validation set. Micrometastatic tumors, neoadjuvant systemic therapy, invasive lobular carcinoma, and histologic grade 3 were associated with lower diagnostic accuracy.
Conclusion
In a challenge competition, accurate deep learning algorithms have been developed, which can be helpful in making frozen diagnosis of intraoperative sentinel lymph node biopsy. Whether this approach has clinical utility will require evaluation in a clinical setting
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