A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer
CANCERS
Authors: Park, In Ja; Yu, Yun Suk; Mustafa, Bilal; Park, Jin Young; Seo, Yong Bae; Kim, Gun-Do; Kim, Jinpyo; Kim, Chang Min; Noh, Hyun Deok; Hong, Seung-Mo; Kim, Yeon Wook; Kim, Mi-Ju; Ansari, Adnan Ahmad; Buonaguro, Luigi; Ahn, Sung-Min; Yu, Chang-Sik
Abstract
Preoperative chemoradiotherapy (PCRT) and subsequent surgery is the standard multimodal treatment for locally advanced rectal cancer (LARC), albeit PCRT response varies among the individuals. This creates a dire necessity to identify a predictive model to forecast treatment response outcomes and identify patients who would benefit from PCRT. In this study, we performed a gene expression study using formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 156 LARC patients (training cohort n = 60; validation cohort n = 96); we identified the nine-gene signature (FGFR3, GNA11, H3F3A, IL12A, IL1R1, IL2RB, NKD1, SGK2, and SPRY2) that distinctively differentiated responders from non-responders in the training cohort (accuracy = 86.9%, specificity = 84.8%, sensitivity = 81.5%) as well as in an independent validation cohort (accuracy = 81.0%, specificity = 79.4%, sensitivity = 82.3%). The signature was independent of all pathological and clinical features and was robust in predicting PCRT response. It is readily applicable to the clinical setting using FFPE samples and Food and Drug Administration (FDA) approved hardware and reagents. Predicting the response to PCRT may aid in tailored therapies for respective responders to PCRT and improve the oncologic outcomes for LARC patients.
Effects of Mycobacterium bovis on monocyte-derived macrophages from bovine tuberculosis infection and healthy cattle
FEMS MICROBIOLOGY LETTERS
Authors: Wang, Yang; Zhou, Xiangmei; Lin, Jingjun; Yin, Fei; Xu, Lihua; Huang, Ying; Ding, Tianjian; Zhao, Deming
Abstract
Bovine tuberculosis (BTB) is a chronic infectious disease caused by the pathogen Mycobacterium bovis and poses a long-standing threat to livestock worldwide. To further elucidate the poorly defined BTB immune response in cattle, we utilized monocyte-derived macrophages (MDMs) to assess the gene expression related to M. bovis Beijing strain stimulation. Here, we demonstrate the existence of distinctive gene expression patterns between macrophages of healthy cattle and those exposed to BTB. In comparing MDMs cells from healthy cattle (n = 5) and cattle with tuberculosis (n = 5) 3 h after M. bovis stimulation, the differential expressions of seven genes (IL1 beta, IL1R1, IL1A, TNF-alpha, IL10, TLR2 and TLR4) implicated in M. bovis response were examined. The expressions of these seven genes were increased in both the tuberculosis-infected and the healthy cattle to M. bovis stimulation, and two of them (TLR2 and IL10) were significantly different in the tuberculosis and the healthy control groups (P <= 0.05). The increase in the expression of the TLR2 gene is more significant in healthy cattle response to stimulation, and the change of IL10 gene expression is more significant in tuberculosis cattle. Additionally, we investigated the cytopathic effect caused by M. bovis stimulation and the relationship between M. bovis and MDMs cells to obtain a general profile of pathogen-host interaction.