Gene Expression Profiling of Cutaneous Injured and Non-Injured Nociceptors in SNI Animal Model of Neuropathic Pain
SCIENTIFIC REPORTS
Authors: Berta, Temugin; Perrin, Florence E.; Pertin, Marie; Tonello, Raquel; Liu, Yen-Chin; Chamessian, Alexander; Kato, Ann C.; Ji, Ru-Rong; Decosterd, Isabelle
Abstract
Nociceptors are a particular subtype of dorsal root ganglion (DRG) neurons that detect noxious stimuli and elicit pain. Although recent efforts have been made to reveal the molecular profile of nociceptors in normal conditions, little is known about how this profile changes in pathological conditions. In this study we exploited laser capture microdissection to specifically collect individual injured and non-injured nociceptive DRG neurons and to define their gene profiling in rat spared nerve injury (SNI) model of neuropathic pain. We found minimal transcriptional changes in non-injured neurons at 7 days after SNI. In contrast, several novel transcripts were altered in injured nociceptors, and the global signature of these LCM-captured neurons differed markedly from that the gene expression patterns found previously using whole DRG tissue following SNI. Pathway analysis of the transcriptomic profile of the injured nociceptors revealed oxidative stress as a key biological process. We validated the increase of caspase-6 (CASP6) in small-sized DRG neurons and its functional role in SNI-and paclitaxel-induced neuropathic pain. Our results demonstrate that the identification of gene regulation in a specific population of DRG neurons (e.g., nociceptors) is an effective strategy to reveal new mechanisms and therapeutic targets for neuropathic pain from different origins.
Prognostic Impact of Polymorphisms in the CASPASE Genes on Survival of Patients with Colorectal Cancer
CANCER RESEARCH AND TREATMENT
Authors: Choi, Jun Young; Kim, Jong Gwang; Lee, You Jin; Chae, Yee Soo; Sohn, Sang Kyun; Moon, Joon Ho; Kang, Byung Woog; Jung, Min Kyu; Jeon, Seong Woo; Park, Jun Seok; Choi, Gyu Seog
Abstract
Purpose This study analyzed potentially functional polymorphisms in CASPASE (CASP) genes and their impact on the prognosis for Korean colorectal cancer patients. Materials and Methods A total of 397 consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in this study. Genomic DNA from these patients was extracted from fresh colorectal tissue, and the 10 polymorphisms in the CASP3, CASP6, CASP7, CASP8, CASP9, and CASP10 genes were determined using a reverse transcription polymerase chain reaction genotyping assay. Results The median patient age was 63 years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had rectal cancer. Univariate and multivariate survival analysis including pathologic stage, patient age, differentiation, and carcinoembryonic antigen level demonstrated that these polymorphisms were not associated with either disease-free or overall survival. Conclusion None of the 10 polymorphisms in the CASP genes investigated in this study was found to be an independent prognostic marker for Korean patients with curatively resected colorectal cancer.