ABSTRACT
BACKGROUND: Studies have shown that the CDK5R1 gene could have a part in some types of cancer. This study sought to examine the relationship between CDK5R1 expression and prognosis and medication resistance in 13 commonly occurring cancers. METHOD: The cancer genome atlas data and clinical data were utilized to assess the role of CDK5R1 in malignancies. The expression data of 13 cancers were also integrated and used for the co-expression network. The relationship between CDK5R1 expression and drug resistance and sensitivity was evaluated using pharmacogenomics data. The colorectal cancer (CRC) and breast cancer (BC) were used to confirm the results through the RT-qPCR method. RESULTS: With the exception of gastric cancer, all common malignancies showed an increase in CDK5R1 expression. Also, outcomes of sensitivity and specificity showed that CDK5R1 level could be a really good potential biomarker. Additionally, CDK5R1 expression was higher in CRC and BC samples compared to adjacent normal, according to RT-qPCR data. In six types of tumors and combined data, a poor prognosis was associated with increased CDK5R1 expression. The CDK5R1-associated genes were connected to the primary oncogenic pathways in cancer cells, according to the co-expression network. Also, CDK5R1 level was significantly linked to the resistance and sensitivity of several chemotherapy drugs and caused the highest resistance to cyclophosphamide. CONCLUSION: CDK5R1 expression is upregulated in 12 prevalent cancers and can play an oncogenic role. Also, this gene's expression could be used as a biomarker to predict patient survival and medication resistance.
Subject(s)
Breast Neoplasms , Colorectal Neoplasms , Humans , Female , Nerve Tissue Proteins/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Oncogenes , Cell Proliferation , Drug Resistance , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/geneticsABSTRACT
Colorectal cancer is the 2nd leading cause of death in humans because of cancer. This rank of death could be due to the high rate of incidence from one hand, and the lack of sufficient diagnostic and therapeutic approaches from the other hand. Thus, molecular tools have been emerging as the potential biomarker to improve the early diagnosis and therapeutic management that subsequently could lead to the heightened survival rate of colorectal cancer patients. Long non-coding RNA (lncRNAs) have shown promising capabilities to be used in clinics. The profiling methods could identify novel aberrantly expressed lncRNAs in colorectal cancer. We, thus, performed a comprehensive and unbiased approach to shortlist the dysregulated lncRNAs based on the colon adenocarcinoma TCGA data. An unbiased in silico method was used to rank the yet to profiled lncRNAs in colorectal cancer. qPCR was used to measure the expression level of selected lncRNAs. Our results nominated ESRG, LINC00518, PWRN1, and TTTY14 lncRNAs as the top-hit novel lncRNAs with aberrant expression in colon cancer. The qPCR method was used to profile these lncRNAs that showed the up-regulation of ESRG and LINC00518, and down-regulation of TTTY14 in thirty paired colorectal cancer specimens. The statistical analyses demonstrated that ESRG, LINC00518 and PWRN1 could distinguish the tumor from normal samples. Moreover, ESRG showed a negative correlation with the overall survival of patients. These diagnostic and prognostic results suggest that profiling ESRG, LINC00518 and PWRN1 s may have implications in clinics.
Subject(s)
Colorectal Neoplasms , RNA, Long Noncoding/metabolism , Aged , Biomarkers, Tumor , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Medical Informatics , Middle Aged , PrognosisABSTRACT
Colorectal cancer is the main cause of human death due to cancer. This fact could be due to the insufficiency of early diagnosis or poor therapeutic strategies. Various molecular tools have been utilized in studies to assess their potentials as diagnostic biomarkers or determining factors in precision medicine. Among these molecules, long non-coding RNAs (lncRNA) have been emerging as accurate and potent transcripts to improve the detection of cancer. The overexpressed lncRNAs could also be deeply studied as the molecules for the targeted therapy in different malignancies, in particular colorectal cancer. Thus, we utilized an unbiased approach to select the up-regulated lncRNAs in colon adenocarcinoma via analyzing the TCGA dataset. Then, we validated the overexpression of two first-ranked lncRNAs, i.e., NPSR1-AS1 and TLX1NB, in our in-house colorectal cancer samples as compared to the paired adjacent normal tissues. The analyses revealed that these lncRNAs could significantly distinguish the tumor against the normal samples. The results may have implications in the early diagnosis and targeted therapy of colorectal cancer.
