Changjing Cai

Changsheng Xing

Jiao Hu

Rui Cao

Ying Han

Frontiers in Genetics

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Editorial: Translational medicine inthe diagnosis and treatment ofcancer based on oncogenetics:from bench to bedsideRui Cao1, Ying Han2, Changjing Cai3*, Jiao Hu4* andChangsheng Xing5*1Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China,2Department of Oncology, Xiangya Hospital, Central South University, Changsha, China, 3National ClinicalResearch Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China,4Department of Urology, Xiangya Hospital, Xiangya School of Medicine, Central South University,Changsha, China, 5Department of Medicine, Keck School of Medicine, University of Southern California,Los Angeles, CA, United StatesKEYWORDStranslation medicine, bench to bedside, diagnosis, treatments, cancerEditorial on the Research TopicTranslational medicine in the diagnosis and treatment of cancer based ononcogenetics: from bench to bedsideCancer is a major public health problem worldwide. Clarifying cancer etiology andpathogenesis is of great significance to its prevention, diagnosis, and treatment. The conceptof translational medicine, which was first mentioned as “bench to bedside” (B to B) patternby Choi (1992), can be a useful method for cancer-related studies. Thus, in this ResearchTopic, we aim to highlight the emerging role of onco-genetics in cancer and discuss thepotential challenges of cancer diagnoses and treatments, from the bench to the bedside.In this Research Topic, Xiao et al. demonstrated the involvement of HOXC-4 in pan-cancer. They investigated the relationship between the expression level of HOXC-4 andprognosis, and additionally, the correlation between HOXC4 and clinical outcome ofimmunotherapy, together with anti-cancer drug sensitivity. This research provided anew potential biomarker in clinical process and shed new light on the anti-tumorimmunotherapy (Xiao et al.).Furthermore, the research of Cheng et al. indicated the advanced lung cancerinflammation index (ALI), which was a powerful prognostic and predictive biomarker inmultiple myeloma (MM) patients and maintained the function of predicting thechemotherapy efficacy in MM patients receiving induction therapy. AMI was apromising biomarker in predicting the clinical outcome of immune checkpoint inhibitorefficacy in advanced non-small-cell lung cancer (Mountzios et al., 2021). In colorectal cancerpatients, the preoperative ALI acted as a role in predicting the compositions and recurrenceafter curative resection (Horino et al., 2022). ALI also takes part in predicting the elderlypatients with heart failure, which serves as an effective nutritional biomarker to predict thepatient with better prognosis with higher ALI (Yuan et al., 2022). ALI exerted prognosisvalue in various kinds of cancers and immune therapy responses, together with heart disease.OPEN ACCESSEDITED AND REVIEWED BYAnton A. Buzdin,European Organisation for Research andTreatment of Cancer, Belgium*CORRESPONDENCEChangjing Cai,vccj07@csu.edu.cnJiao Hu,hujiao@csu.edu.cnChangsheng Xing,cxing999@usc.eduRECEIVED 21 April 2023ACCEPTED 02 November 2023PUBLISHED 13 November 2023CITATIONCao R, Han Y, Cai C, Hu J and Xing C(2023), Editorial: Translational medicinein the diagnosis and treatment of cancerbased on oncogenetics: from benchto bedside.Front. Genet. 14:1210094.doi: 10.3389/fgene.2023.1210094COPYRIGHT©2023 Cao, Han, Cai, Hu and Xing. This isan open-access article distributed underthe terms of the Creative CommonsAttribution License (CC BY). The use,distribution or reproduction in otherforums is permitted, provided the originalauthor(s) and the copyright owner(s) arecredited and that the original publicationin this journal is cited, in accordance withaccepted academic practice. No use,distribution or reproduction is permittedwhich does not comply with these terms.Frontiers in Genetics frontiersin.org01TYPE EditorialPUBLISHED 13 November 2023DOI 10.3389/fgene.2023.1210094In the future, ALI may provide new therapy for cancer orcardiovascular diseases in the aspect of nutrition.Neoadjuvant chemotherapy (NAC) is the standard treatmentfor muscle-invasive bladder cancer (MIBC), while the response ofthe NAC is still unclear for part of the MIBC patients (Hermanset al., 2018). The research by Li et al. constructed a signature topredict the prognosis of the patient and the clinical outcome andtreatment of NACwith the help of bioinformatic analysis. The five-gene-based risk score predicted the NAC response with highaccuracy, which might provide individualized treatment foreach of different stage or pathological types of patients withmore dawn.RNA modification writer is widespread on all nucleotides andthe modification is at the RNA level (Chen et al., 2021a). RNAmodifying proteins may serve as a series of antitumor targets fordrug discovery. The process of tumor formation also includes epi-transcriptome, which has been a hot Research Topic recently (Heet al., 2019). The research of Cheng and Yi established a newsignature which was associated with the distinct RNAmodification clusters to test and verify the relationship betweenthe signature and the related biological process, which was related tothe tumor signaling pathway, tumor microenvironment, and clinicaloutcome. This research has provided new insight into the earlydiagnoses and treatment of cancer.Ferroptosis is an advanced type of programmed cell death and isintensively connected to maintaining homeostasis and thedevelopment of detrimental diseases, especially tumorigenesis(Chen et al., 2021b). In recent years, researchers have found therole of lipid and mitochondria metabolism regulates ferroptosis inhead and neck cancer drug-resistant (Wu et al., 2020). In theresearch of our Research Topic, Wei et al.conclude 47 genesrelated to ferroptosis and obtain the relation to the prognosis aswell as immune signatures of head and neck squamous cancer(HNSCC) patients. The authors also assessed their conclusion indifferent clinical cohorts constructed by the FPRS scoring system.Thus, it provides a new prediction target and a therapeuticimplication in clinical practice. Meanwhile, Yao et al. found thatanother cell death type, cuproptosis, has a close relationship with theprognosis of kidney renal clear cell carcinoma.Interferon-γ (IFN-γ) plays a critical role in signaling pathwayalterations in cancers (Jorgovanovic et al., 2020). At present,researchers have reported the inhibition of ER stress obviouslyprevents IFN-γ-triggered apoptosis, causing IFN-γ-mediatedanticancer responses in lung cancers (Fang et al., 2021). As forDeng et al. research, an IFN-γ-related signature was found for itsremarkable roles in the regulation of tumor progression, immuneresponse, mutation, and tumor microenvironment in bladdercancer. The enhanced understanding of the IFN-γ-relatedsignature would be expected to apply in clinic in the near futureand be validated in more clinical cohorts.Alkaline ceramidase 2 (ACER2) is an enzyme located in theGolgi complex participating in sphingolipid metabolizing, which isupregulated in most types of cancer (Xu et al., 2018). Liu et al.revealed that the expression level of ACER2 was correlated withbladder cancer in various aspects. Tumor microenvironment andimmune checkpoint were hot research topics in cancer thatcorrelate with ACER2 expression level significantly.Furthermore, ACER2 predicted the molecular subtypes tofurther estimate the immunotherapy response obliquely.Additionally, the ACER2 also obtained the ability to predict theclinical outcome of chemotherapy and immune therapy directlyand accurately. The study also revealed that the ACER2 issignificantly upregulated in other types of cancers, which mayprovide new insight into cancer treatment or new cancerbiomarkers in the future.In bone vascular endothelial cells, the immunolabeling ofPECAM1 was revealed to show the vascular network (Wanget al., 2019). However, the tumor premetastatic environment canbe formed before dissemination due to the tumor-derived factorsreleased from primary tumors, including several growth factorsassociated with vascular networks (Wang et al., 2020). Thus weshould attach importance to PECAM1 and bone metastases. In theresearch of Liang et al., they analyze the association and find thatPECAM1 could be recognized as the potential biomarker thatsignifies the diagnosis and treatment of bone metastases andverified in bone metastatic tumor tissues. But there is also alimitation because the tissues in need were difficult to harvest.Thus, the authors believed the enlargement of the sample sizewas necessary and would continue collecting as many tissuesamples as possible.The PTPN family genes are promising prognostic biomarkersand therapeutic targets for various cancers. But the distinct roles ofthe PTPN family in acute myeloid leukemia (AML) have not yetbeen explored entirely. Liu et al. performed a comprehensiveanalysis which focused on the PTPN family expression profileand prognostic significance in AML. They screened out severaldifferentially expressed PTPN family genes in AML. Especially,PTPN6 was one of these members and may be used as an AMLdiagnostic and prognostic marker (Liu et al.).ZNF281 (zinc finger protein 281) plays critical roles inregulating embryonic stem cell (ESC) differentiation andmaintaining cellular stemness. Hou et al. performed a pan-canceranalysis and indicated that ZNF281 was overexpressed in variouscancers and related to shorter survival. Then, they correlated theZNF281 with immune characters in tumor microenvironment.Overall, they provided new insights into the dual role ofZNF281 and approved that it was a potential biomarker forregeneration and tumor prognosis. Similarly, Guo et al.performed a pan-cancer analysis focused on Methylmethanesulfonate-sensitivity protein 22-like (MMS22L). Theyrevealed the essential role of MMS22L as a tumor-regulating genein human cancers while further emphasizing its feasibility as a novelmolecular marker in hepatocellular carcinoma. Their findingsprovide an essential reference for the study of MMS22L intumors. Meanwhile, Bao et al. found that overexpression ofSPAG6 and low expression of NM23 are negatively related to thepathological grade, metastasis, and enneking stage and prognosis ofosteosarcoma patients. This suggested that SPAG6 andNM23 should be considered candidate prognostic biomarkers forpatients with osteosarcoma. Tang et al. confirmed FN1 is thepotential novel biomarker for predicting poor prognosis andradio-resistance in HNSCC patients. Overexpression of FN1 playsan important role in the tumorigenesis, prognosis, and radio-resistance of HNSCC.Taking advantage of novel computational approaches, publiclyavailable datasets can be utilized to provide new scientificFrontiers in Genetics frontiersin.org02Cao et al. 10.3389/fgene.2023.1210094hypotheses. In this Research Topic, Ma and Yu identified the ADAMfamily as novel pan-cancer biomarkers for patient prognosis andpotential clinical responses, using bioinformatics analyses andexperimental approaches. The authors comprehensively analyzedthe differential expression levels of ADAMs in multiple types ofcancers, and explored the correlations between ADAMs and tumormicroenvironment, stemness, immune subtype, and sensitivities tochemotherapy and immunotherapy. Since cancer immunotherapyshows impressive efficacy but limited responses inmajority of cancerpatients, the identification of new therapeutic targets will surelybenefit the therapeutic decision-making and prediction of clinicaloutcomes.In conclusion, it is our great honor to successfully recruit andattract numerous researchers to this Research Topic, who havecontributed plenty of advanced, fascinating, and importantworks. However, limited by the present situation, we can onlypublish part of these articles which we believe are moreapplicable to our Research Topic. We believe with theprogression of “B to B” studies, cancer treatments will beenormously improved, and eventually, future cancer patients willbenefit from these research works.Author contributionsRC, CC, CX, and JH wrote the article. YH and CX edited andrevised the manuscript. All authors contributed to the article andapproved the submitted version.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of the authorsand do not necessarily represent those of their affiliated organizations,or those of the publisher, the editors and the reviewers. Any productthat may be evaluated in this article, or claim that may be made by itsmanufacturer, is not guaranteed or endorsed by the publisher.ReferencesChen, H., Yao, J., Bao, R., Dong, Y., Zhang, T., Du, Y., et al. (2021a). Cross-talk of fourtypes of RNA modification writers defines tumor microenvironment andpharmacogenomic landscape in colorectal cancer. Mol. Cancer 20, 29. doi:10.1186/s12943-021-01322-wChen, X., Kang, R., Kroemer, G., and Tang, D. (2021b). Broadening horizons: the roleof ferroptosis in cancer. Nat. Rev. Clin. Oncol. 18, 280–296. doi:10.1038/s41571-020-00462-0Choi, D. W. (1992). Bench to bedside: the glutamate connection. Science 258,241–243. doi:10.1126/science.1357748Fang, C., Weng, T., Hu, S., Yuan, Z., Xiong, H., Huang, B., et al. (2021). IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells.Oncoimmunology 10, 1962591. doi:10.1080/2162402X.2021.1962591He, L., Li, H.,Wu,A., Peng, Y., Shu, G., andYin,G. (2019). Functions ofN6-methyladenosineand its role in cancer. Mol. Cancer 18, 176. doi:10.1186/s12943-019-1109-9Hermans, T. J. N., Voskuilen, C. S., Van Der Heijden, M. S., Schmitz-Dräger, B. J.,Kassouf, W., Seiler, R., et al. (2018). Neoadjuvant treatment for muscle-invasive bladdercancer: the past, the present, and the future. Urol. Oncol. 36, 413–422. doi:10.1016/j.urolonc.2017.10.014Horino, T., Tokunaga, R., Miyamoto, Y., Hiyoshi, Y., Akiyama, T., Daitoku, N., et al.(2022). The advanced lung cancer inflammation index is a novel independentprognosticator in colorectal cancer patients after curative resection. Ann.Gastroenterol. Surg. 6, 83–91. doi:10.1002/ags3.12499Jorgovanovic, D., Song, M., Wang, L., and Zhang, Y. (2020). Roles of IFN-γ in tumorprogression and regression: a review. Biomark. Res. 8, 49. doi:10.1186/s40364-020-00228-xMountzios, G., Samantas, E., Senghas, K., Zervas, E., Krisam, J., Samitas, K., et al.(2021). Association of the advanced lung cancer inflammation index (ALI) withimmune checkpoint inhibitor efficacy in patients with advanced non-small-cell lungcancer. ESMO Open 6, 100254. doi:10.1016/j.esmoop.2021.100254Wang, Q., Liu, K., Yang, L., Wang, H., and Yang, J. (2019). BoneClear: whole-tissueimmunolabeling of the intact mouse bones for 3D imaging of neural anatomy andpathology. Cell Res. 29, 870–872. doi:10.1038/s41422-019-0217-9Wang, M., Xia, F., Wei, Y., and Wei, X. (2020). Molecular mechanisms and clinicalmanagement of cancer bone metastasis. Bone Res. 8, 30. doi:10.1038/s41413-020-00105-1Wu, Y., Yu, C., Luo, M., Cen, C., Qiu, J., Zhang, S., et al. (2020). Ferroptosis in cancertreatment: another way to rome. Front. Oncol. 10, 571127. doi:10.3389/fonc.2020.571127Xu, R., Garcia-Barros, M., Wen, S., Li, F., Lin, C. L., Hannun, Y. A., et al. (2018).Tumor suppressor p53 links ceramide metabolism to DNA damage response throughalkaline ceramidase 2. Cell Death Differ. 25, 841–856. doi:10.1038/s41418-017-0018-yYuan, X., Huang, B., Wang, R., Tie, H., and Luo, S. (2022). The prognostic value ofadvanced lung cancer inflammation index (ALI) in elderly patients with heart failure.Front. Cardiovasc Med. 9, 934551. doi:10.3389/fcvm.2022.934551Frontiers in Genetics frontiersin.org03Cao et al. 10.3389/fgene.2023.1210094

Editorial: Translational medicine in the diagnosis and treatment of cancer based on oncogenetics: from bench to bedside

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Editorial: Translational medicine in the diagnosis and treatment of cancer based on oncogenetics: from bench to bedside

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