Editorial: Application of advances in molecular and genetic researches to tackle pancreatic cancer: screening, diagnosis, prognostication and drug response prediction
Year: 2023
Type: editorial
Abstract: The incidence and mortality rates of pancreatic cancer are widely different; nations with high or very high Human Development Indexes have roughly five times higher rates when compared to low or medium countries. Age affects the incidence rates for both genders, with elderly adults over 70 having the highest rates and people older than 55 account for 90% of all incidences of pancreatic cancer.Moreover, it has a very poor prognosis with five years survival does not exceed 5% of the diagnosed cases in the best scenario. This nightmare prognosis is attributed to various factors such as aggressive nature, chemoresistance and late stage diagnosis. The delay in the diagnosis of pancreatic is attributed the no specific symptoms, poor public awareness, lack of early screening tests and difficult pancreatic anatomy which makes even advanced radiological diagnosis difficult.The molecular signature of pancreatic cancer is mainly centered around a handful bunch of rug genes such as KRAS, P53, CDKN24,SMAD4 and BRCA 1&2. Unlike many of other tumors no druggable offending gene was found in pancreatic cancer which made molecular treatment not on the table.The above facts made the pancreatic cancer a fertile land for basic, preclinical and clinical researches which gave us the motivation and the courage to allocate a research topic in the frontiers of genetics aiming to bring together the latest studies in the field.The first paper by Döring, Peer et al. (2023) investigated the prevalence of germline pathogenic variants in calcitonin-producing pancreatic neuroendocrine neoplasms in a cohort of five Tawin's patients using whole genome sequencing.The study found single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8 as well as structural variants in CDC25C and USP44. This combination of variants make a special molecular signature for this specific a tumor that might be used in the future for prognostic and purposes. The authors argue that germline mutations have larger contribution in the pathogenesis of the disease. This work despite its importance, its scientific value might have been affected by its small sample size.Immunotherapy has been a very hotspot for cancer research, A research conducted by Zhu, Teng et al. (2023) investigated the role of Krüppel-like factor 3 (KLF3) which is a key transcriptional repressor, in the microenvironment of pancreatic cancer. This study is, in part, database dependent, in addition to in vivo (mouse model) and in vitro (cell line) work.The outcome of the study showed that KLF3 was involved in various immune and progression -related pathways since its expression is higher in tumors than normal tissues and even higher in aggressive tumors. Its silencing was associated with slower rate of tumor progression. Indeed, its high expression is associated with poor response to immunotherapy. This marker opens the door to immunotherapy in pancreatic cancer and might be used as part of prognostic system. Guo, Wu et al. (2023) tried to established a prognostic and predictive scores for pancreatic ductal carcinoma that utilized Ubiquitination related genes (URGs). URGs have been reported as regulators of tumors, affecting tumor cell cycle regulation, gene expression, and progression.The authors used two cancer data bases; the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), to establish a prognostic and predictive systems for pancreatic ductal carcinoma in addition to cell culture work for functional studies. A special system was used to establish URGs prognostic signature depending on three Ubiquitination related genes (SLC22A17, UCHL1 and S100A2) that are involved in many of cancer pathogenesis .The research group summarized their research conclusion (we designed a molecular cluster and prognostic signature based on URGs, which aid in anticipating survival, directing immunotherapy, and determining clinical outcomes. This research potentially provides deeper insights into the function of ubiquitination in PDAC and facilitates the development of more effective therapies for this disease). Chung, Lin et (2023) think that germline mutations have a greater contribution to PDAC and the previous studies has underestimated their role due to selection of coding areas of limited number of genes. In the current work the authors selected 24 Taiwan's patients and performed genome sequencing for their peripheral blood cells for 750 genes with diverse genetic variant types such as SNP, small insertions and deletions and inversions.Paired-end reads were aligned to the reference genome (GRCh38/hg38) using BWA-MEM to identify germline mutations.Almost one third of the cases had germline mutation in mainly five genes ATM, BRCA1, BRCA2, POLQ, and SPINK1 with unequivocal role in pancreatic cancer pathogenesis . Other genes were not of strong contribution to PDAC. The study emphasize the role of these mutation in pathogenesis of cancer and might be future prognostic and predictive molecular candidate.
Source: Frontiers in Genetics
Authors: Salih Ibrahem, Saleh AlGhamdi
Institutions: University of Kirkuk, King Fahd Medical City
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4388941371