Biology-guided precision medicine in rare cancers: Lessons from sarcomas and neuroendocrine tumours

Graaf, Winette T.A. van der; Tesselaar, M.E.T.; McVeigh, Terri P; Oyen, W.J.G.; Fröhling, Stefan

doi:10.1016/j.semcancer.2022.05.011

Cited by 12 publications

(5 citation statements)

References 141 publications

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“…The main pillar of radical SARC treatment is surgery, which is usually sufficient for low-grade tumors [ 35 ]. However, once metastasis occurs, the median survival of patients is often unsatisfactory [ 36 ]. Reliable and sensitive biomarker is essential for early diagnosis, inhibition of disease progression and improved prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of an ADME-related gene for forecasting the prognosis and responding to immunotherapy in sarcomas

Wang,

et al. 2024

Eur J Med Res

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There are more than 170 subtypes of sarcomas (SARC), which pose a challenge for diagnosis and patient management. Relatively simple or complex karyotypes play an indispensable role in the early diagnosis and effective treatment of SARC. The genes related to absorption, distribution, metabolism, and excretion (ADME) of a drug can serve as prognostic biomarkers of cancer and potential drug targets. In this study, a risk score signature was created. The SARC cohort was downloaded from The Cancer Genome Atlas (TCGA) database, and divided into high-risk group and low-risk group according to the median value of risk score. Compared with high-risk group, low-risk group has a longer survival time, which is also verified in osteosarcoma cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. In addition, the relationship between the signature and immunophenotypes, including status of immune cell infiltration and immune checkpoint expression, was explored. Then, we found that high-risk group is in immunosuppressive status. Finally, we verified that PPARD played a role as a carcinogen in osteosarcoma, which provided a direction for targeted treatment of osteosarcoma in the future. Generally speaking, the signature can not only help clinicians predict the prognosis of patients with SARC, but also provide a theoretical basis for developing more effective targeted drugs in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of an ADME-related gene for forecasting the prognosis and responding to immunotherapy in sarcomas

Wang,

et al. 2024

Eur J Med Res

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“…Sarcomas typically have reoccurring driver genomic events, covering amplification, mutations, or translocations (Baumhoer et al, 2019;Jagodzinska-Mucha et al, 2021;van der Graaf et al, 2022). For instance, undifferentiated sarcomas frequently undergo recurrent copy number mutations, and deletions of oncogenes, such as TP53, RB1, CDKN2A, and CDKN2B, are common (Hames-Fathi et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-associated lncRNAs discern prognosis and immune microenvironment in sarcoma victims

Chu

Zheng

et al. 2022

Front. Cell Dev. Biol.

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Cuproptosis is a fresh form of the copper-elesclomol-triggered, mitochondrial tricarboxylic acid (TCA) dependent cell death. Yet, the subsumed mechanism of cuproptosis-associated lncRNAs in carcinoma is not wholly clarified. Here, We appraised 580 cuproptosis-associated lncRNAs in sarcoma and thereafter construed a module composing of 6 cuproptosis lncRNAs, entitled CuLncScore, utilizing a machine learning methodology. It could outstandingly discern the prognosis of patients in parallel with discriminating tumor immune microenvironment traits. Moreover, we simulate the classification system of cuproptosis lncRNAs by unsupervised learning method to facilitate differentiation of clinical denouement and immunotherapy modality options. Notably, Our Taizhou cohort validated the stability of CuLncScore and the classification system. Taking a step further, we checked these 6 cuproptosis lncRNAs by Quantitative real-time polymerase chain reaction (qRT-PCR) to ascertain their authenticity. All told, our investigations highlight that cuproptosis lncRNAs are involved in various components of sarcoma and assist in the formation of the tumor immune microenvironment. These results provide partial insights to further comprehend the molecular mechanisms of cuproptosis lncRNAs in sarcoma and could be helpful for the development of personalized therapeutic strategies targeting cuproptosis or cuproptosis lncRNAs.

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“…NENs consist of a heterogeneous group of neoplasms that can occur in almost all sites, most frequently in the digestive and respiratory system [2,3]. The steady increase of NENs over the past decades has received global attention, accordingly, tremendous efforts have been made in AGING superior classification, molecular diagnosis, radionuclide, and targeted therapies of NENs [3][4][5][6][7]. However, the epidemiological characteristics and prognostic factors, crucial for early perception and risk stratification, have not been fully understood, particularly for women patients.…”

Section: Introductionmentioning

confidence: 99%

The crucial role of age and site in incidence and prognosis of female neuroendocrine neoplasms in the United States: a population-based study from 2000 to 2018

Xiao,

Xu,

Zhang

et al. 2024

Aging

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Background: As the incidence continues to rise, global concern about neuroendocrine neoplasms (NENs) is mounting. However, little is known about how NENs affect women patients. Methods: The annual percentage change (APC) was calculated to describe the incidence. Cox proportional hazards multivariable regression was used to identify risk factors. The nomograms were employed to estimate prognosis. Results: A total of 39,237 female NENs (fNENs) cases were identified. The incidence of fNENs increased annually (APC = 4.5, 95% CI 4.1-4.8, P < 0.05), and the incidence pattern and survival outcomes showed age and site-specificity. Appendiceal, rectal, and pulmonary fNENs were major contributors to the incidence of patients younger than 40, between 40-59, and over 60 years old, respectively. The Cox proportional hazards regression model revealed that age, tumor size, grade, stage, and primary sites were closely related to survival. The worst survival outcomes appeared in breast, reproductive system, and liver fNENs for patients under 40, between 40-49, and over 50 years old, respectively. A nomogram based on these developed with higher predictive accuracy of prognosis, with a C index of 0.906 in the training cohort and 0.901 in the validation cohort. Conclusions: Our findings revealed distinct site-specific tendencies in the incidence and survival patterns among fNEN patients across various age groups. Thus, reasonable patient screening and stratification strategies should be implemented, especially for young patients.

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Biology-guided precision medicine in rare cancers: Lessons from sarcomas and neuroendocrine tumours

Cited by 12 publications

References 141 publications

Identification of an ADME-related gene for forecasting the prognosis and responding to immunotherapy in sarcomas

Identification of an ADME-related gene for forecasting the prognosis and responding to immunotherapy in sarcomas

Cuproptosis-associated lncRNAs discern prognosis and immune microenvironment in sarcoma victims

The crucial role of age and site in incidence and prognosis of female neuroendocrine neoplasms in the United States: a population-based study from 2000 to 2018

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