Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and liver metastasis remains the major cause of death in CRC. Extensive genomic analysis provided valuable insight into the pathogenesis and progression of CRC. However, the major proteogenomic characterization of CRC liver metastasis is still unknown. We investigated proteogenomic characterization and performed comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.
Project description:We performed a comprehensive proteogenomic profiling of cervical cancer (CC) tumors obtained from 139 Chinese women. This study provides a valuable public resource including proteomic, phosphoproteome, acetylproteome for researchers and clinicians to delve deeper into molecular causes of CC, and to identify potential treatments and advance clinical practice.
Project description:Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n=16; FH-mutation confirmed) and non-syndromic (NS) patients (n=12) identified a significantly higher protein:transcript correlation in HLRCC (R=0.35) vs. NS ULMs (R=0.242, MWU p=0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC=1.86, MWU p<0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.
Project description:We report proteogenomic analysis of diffuse gastric cancers (GCs) in young population. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs.
Project description:Cervical cancer (CACX) is the tumor of the uterine cervix and its primary etiological factor is the infection of high risk human papilloma virus (hrHPV), primarily HPV16 and HPV18. CACX is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. In India, CACX accounts for approximately 1,22,844 new cases and 67,477 deaths annually. It is evident that Indian women are getting diagnosed at invasive stages of CACX leading to poor prognosis. Here, we tried to understand the change in the expression profile during the development of the tumor starting from HPV-negative normal samples to invasive CACX samples and try to understand the pathogenesis of cervical carcinoma in Indian patients.
Project description:Cancer of the uterine cervix (CACX) is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. In India, CACX accounts for approximately 1,22,844 new cases and 67,477 deaths annually. Previously, we catalogued global copy-number aberrations [GSE76911] and performed gene expression profiling [GSE122697] in CACX. Interestingly, differential change in the expression between normal and tumor tissues of several genes did not correlate with the chromosomal copy-number alteration. This encouraged us to perform genome-wide DNA methylation analysis. Hence, in the current study, we discover the global methylation in cervical tumors at different clinical stages and HPV-negative normal ectocervix along with HPV16-positive cervical squamous cell carcinoma cell line, SiHa.