The pan‐cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target

Abstract

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship

“…In another pan-cancer analysis, the expression of the FAM72 family was generally upregulated in most tumors, including TGCT [73]. Interestingly, the member FAM72A was downregulated in TGCT as opposed to most cancers.…”

“…This member's expression seems to have been positively correlated with DNMTs expression and was further studied in relation with cancer stemness. It included methylation-based stemness scores, but no significant association was found in TGCT [73]. FAM99A gene, which codes for an lncRNA, had a lower expression in TGCT compared with normal tissue of the GTEx database; however, further investigations found a positive correlation with four methylation probe sites, and no prognostic value was considered for this cancer type, given the limitations of the study [62].…”

Comprehensive analysis of the prognosis and biological significance of RORβ in head and neck squamous cell carcinoma

“…We integrated all independent clinicopathological prognostic factors from Cox regression analysis to construct a nomogram for evaluating the 1‐, 3‐, and 5‐year OS probability of HNSCC patients 20 . Calibration curves were drawn for the nomogram, the accuracy of the nomogram was evaluated and verified by the consistency index (C‐index).…”

Systematic analysis of the prognostic and immunological role of DHX33 in pan‐cancer

“…Albeit significant advancements have been made in surgical techniques, chemotherapy, and other treatment approaches, the 5‐year survival rate of patients with cancer in China remains far from satisfactory 8,9 . Considering the increase in cancer‐related incidence and mortality rates, the complexity of tumors, and the heterogeneity of humans, it is important to utilize pan‐cancer studies to evaluate potential new prognostic targets and investigate possible pathogenic mechanisms 10–13 …”

“…8,9 Considering the increase in cancerrelated incidence and mortality rates, the complexity of tumors, and the heterogeneity of humans, it is important to utilize pan-cancer studies to evaluate potential new prognostic targets and investigate possible pathogenic mechanisms. [10][11][12][13] DHX33 belongs to the DEAH-box RNA helicase family and plays a key role in activating the NLRP3 inflammasome by regulating ribosome biogenesis. 14 A previous study showed that DHX33 is a direct transcriptional target of Ras signaling in lung cancer cells.…”