Bioinformatics analysis and the clinical significance of TP73 in regulating the immune microenvironment and chemosensitivity of endometrial cancer

Summary

Keywords

TP73, Endometrial cancer, Immune microenvironment, Chemosensitivity

Introduction

Endometrial cancer is the most common gynecological tumor, and its incidence continues to increase globally

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. The 1-year, 3-year, and 5-year survival rates for domestic patients are 96.8%, 89.9%, and 82.1%, respectively. Pathological type, histological grade, clinical stage, and cervical involvement have been confirmed as independent prognostic risk factors

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. However, significant challenges remain in the early diagnosis and prognostic assessment of endometrial cancer, primarily because of the lack of early diagnostic biomarkers and insufficient prognostic evaluation indicators

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. Therefore, new biomarkers are needed to improve the early diagnosis and prognostic evaluation of endometrial cancer.

TP73 belongs to the TP53 gene family and produces N-terminal and C-terminal protein isoforms through alternative promoters, alternative translation initiation, and alternative splicing. Notably, p73 protein isoforms may contain a p53-like transactivation domain (TAp73 isoform) or lack this domain (ΔTAp73 isoform), and these variants have opposing or independent functions

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. Multiple studies have shown that abnormal expression of TP73 in various tumors is closely related to tumorigenesis and tumor progression. Meta-analyses have indicated that the TP73 G4C14-A4T14 polymorphism significantly increases overall cancer risk, with a higher risk in patients with gynecological tumors

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. In cervical cancer, the protein expression of TP73 is significantly greater than that in normal cervical epithelium, and high expression is associated with early-stage disease, fewer lymph node metastases, and better overall survival

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. The expression and functional regulation of the TP73 gene are not mediated by a single molecule. Its transcription, splicing, and isoform balance are also precisely regulated by upstream and downstream regulatory molecules, among which epigenetic regulation by antisense long noncoding RNAs (lncRNAs) is among the key mechanisms. Owing to its natural genomic adjacency to TP73, the TP73-associated antisense lncRNA TP73-AS1 serves as a specific regulatory molecule for TP73 function. This lncRNA is located on chromosome 1p36.32 and has a tail-to-tail antisense transcription pattern relative to that of TP73. It can inhibit the methylation of the TP73 promoter by binding to lysine demethylase 5A (KDM5A) while simultaneously interfering with the alternative splicing of TP73 mRNA. This ultimately leads to a biased suppression of tumor-suppressive TAp73 isoform expression, directly reshaping the functional balance of TP73 isoforms

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. Consequently, TP73-AS1 is upregulated in various gynecological cancers, and its pro-oncogenic functions are closely linked to the regulation of TP73 isoforms. In ovarian cancer, TP73-AS1 modulates TP73 isoforms to regulate the expression of MMP2 and MMP9, promoting tumor cell invasion and metastasis

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; in cervical cancer, this lncRNA exerts its procancer effects through the miR-329-3p/ARF1 axis, and ARF1, as a downstream target gene of TP73, is also indirectly regulated by the TP73 isoform profile

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In this study, bioinformatics methods were used to analyze the total expression levels and mutation characteristics of the TP73 gene in endometrial cancer tissues, explore its association with tumor development and patient prognosis, and systematically investigate the role of this gene in regulating the immune microenvironment of endometrial cancer and modulating chemotherapeutic drug sensitivity. Owing to the lack of standardized annotations and specific detection probes for TP73 isoform-specific transcripts in the TCGA and GTEx databases used in this research, accurate quantification of TAp73 and ΔTAp73 isoform expression levels could not be achieved; hence, this study did not differentiate between the two for analysis. Current research on TP73 in endometrial cancer remains in the preliminary exploratory stage, with unclear correlations between its total expression characteristics and patient clinicopathological parameters and prognosis, as well as undefined specific regulatory mechanisms in tumor immune microenvironment remodeling and chemotherapeutic drug response. These research gaps make it difficult to define the functional and clinical application value of TP73 in endometrial cancer development.

This study relies on public databases such as TCGA and GTEx to conduct the first systematic analysis of the total expression level, gene mutation characteristics, protein interaction network, and downstream regulatory pathways of TP73 in endometrial cancer. We also explored for the first time the correlation between its expression and tumor-infiltrating immune cells, immune molecule expression, and the half-maximal inhibitory concentration (IC₅₀) values of commonly used clinical chemotherapeutic drugs, clarifying its diagnostic and prognostic value. This study proposes a core hypothesis: TP73, as a key regulatory molecule in endometrial cancer, participates in tumorigenesis, malignant progression, and therapeutic response regulation through a multidimensional synergistic mechanism involving remodeling of the tumor immune microenvironment infiltration landscape, regulation of chemotherapeutic drug cellular sensitivity, and the mediation of tumor-associated protein interactions and signaling pathway activation. Differences in its expression levels may lead to imbalances in these mechanisms, affecting tumor immune escape, chemotherapy resistance, and patient clinical outcomes, making TP73 a potential target for endometrial cancer diagnosis and precision therapy. This research aims to fill existing gaps by clarifying the potential value of TP73 as a diagnostic biomarker for endometrial cancer, deciphering its molecular characteristics in regulating the tumor immune microenvironment and chemotherapy sensitivity, and providing preliminary theoretical evidence for the use of total TP73 expression as a diagnostic marker and therapeutic target. The differential functional roles of TAp73 and ΔTAp73 isoforms will be the focus of subsequent studies employing subtype-specific detection methods.

Materials and methods

Results

Discussion

Changes in modern lifestyles and an increase in average life expectancy have led to a yearly increase in the incidence of endometrial cancer, with a trend toward younger age groups. In some developed cities in China, the incidence rate of endometrial cancer has already ranked first among gynecological malignancies

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. Current main treatment options for advanced endometrial cancer include surgical therapy combined with radiotherapy and chemotherapy supplemented by endocrine therapy

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. TP73, also known as p73, is an important member of the TP53 gene family. Proteins encoded by genes in this family typically have two isoforms, TA and DN, where the TA isoform has tumor-suppressive functions and the DN isoform has procancer activity. The biological role of the TP73 gene in the body is primarily determined by the expression level of the DN isoform and the ratio of TA to DN isoform expression. TA-p73 can inhibit cancer development and progression by regulating autophagy, suppressing angiogenesis, interfering with tumor cell drug resistance, and promoting tumor cell apoptosis. However, under certain conditions, it may also promote tumor progression by increasing oxidative stress responses, upregulating rate-limiting enzyme expression, and aiding tumor cells in serine metabolism and proliferation

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. p73 is highly expressed in various tumor tissues, where it promotes cell proliferation, accelerates cell aggregation, and inhibits apoptosis alongside the p53 protein, thereby driving tumorigenesis and progression

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This study revealed that the expression level of TP73 is significantly elevated in endometrial cancer tissues and that the expression level of TP73 is associated with various clinicopathological features. This conclusion is consistent with the expression pattern of TP73 in other gynecological malignancies. High expression of TP73 is related to early tumor stage and fewer lymph node metastases

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. Additionally, the expression level of TP73 significantly differed among patients with different histological subtypes, TP53 mutation statuses, and menopausal statuses. In this study, the phenomenon of high TP73 expression in the TP53 nonmutated group and endometrioid adenocarcinoma, seemingly contradictory to the characteristics of high-malignancy subtypes such as serous carcinoma and the TP53-mutated type, is actually the combined effect of functional specificity of the TP73 subtype, antagonistic regulation within the p53 family, and molecular heterogeneity among endometrial cancer subtypes. The function of TP73 is not determined by its total expression level but is dominated by the TAp73/ΔNp73 subtype ratio. As a dominant-negative subtype, ΔNp73 can form heterodimers with wild-type TP53 and TAp73, blocking tumor-suppressive pathways mediated by both proapoptosis and cell cycle arrest

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. Endometrioid adenocarcinoma is predominantly TP53 wild-type, and tumor cells selectively upregulate the ΔNp73 subtype to escape its tumor-suppressive function, thereby increasing total TP73 expression. In contrast, highly malignant subtypes, such as serous carcinoma, are mostly TP53-mutated, where TP53 function is lost, eliminating the need for ΔNp73-mediated antagonistic regulation. Additionally, mutant TP53 can directly perform pro-oncogenic functions, ultimately leading to the downregulation of total TP73 expression

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. This also explains how differences in its expression levels reflect heterogeneity in tumor biological behavior. ROC curve analysis revealed that the AUC value of TP73 for the diagnosis of endometrial cancer was 0.895, indicating that TP73 has good diagnostic performance and could serve as a potential diagnostic biomarker. The TP73 gene mutation rate is only 4%, but patients with mutations have significantly shorter survival periods. However, in this study, only the correlation between TP73 and overall survival of patients at the level of overall genetic alterations was analyzed, and stratified survival analysis was not conducted on the basis of specific genetic alteration types, such as amplification, truncating mutations, or missense mutations. Considering the low mutation rate of TP73 (only 4%), its significant association with survival is more likely driven by relatively common gene amplification. The lack of stratified analysis by genetic alteration type makes it difficult to precisely distinguish the independent regulatory effects of different variants on endometrial cancer prognosis. Subsequent studies could clarify the regulatory mechanisms of various TP73 genetic alteration types through stratified analysis.

Protein interaction network analysis revealed close interactions between TP73 and tumor-related proteins such as TP53, TP63, and YAP1. As a member of the p53 family, TP73 can form homodimers or heterodimers with TP53 and TP63 to regulate the transcription of downstream target genes, which together participate in tumor suppression-related biological processes such as cell cycle arrest and apoptosis initiation. This interaction pattern has been confirmed in various malignant tumors

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. YAP1 is a key effector molecule of the Hippo pathway that is abnormally activated in endometrial cancer. Its interaction with TP73 serves as a specific regulatory mechanism for the DNA damage response in endometrial cancer cells. Under DNA damage stress induced by chemotherapeutic agents such as cisplatin or ionizing radiation, YAP1 in endometrial cancer cells is phosphorylated at Y357, after which it subsequently forms a stable functional complex with TP73. This complex selectively binds to the promoter regions of pro-apoptotic genes downstream in endometrial cancer cells, activating their transcription and further triggering the mitochondrial apoptosis pathway, thereby enhancing the sensitivity of endometrial cancer cells to DNA damage-inducing therapeutic agents

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. In TP53-mutant endometrial serous carcinomas with a defective p53-mediated DNA damage response, the YAP1-TP73 complex becomes the primary compensatory pathway for DNA damage-induced apoptosis, serving as a critical molecular basis for the chemotherapy response in highly malignant endometrial cancers. This dual role regulates tumor progression and guides clinical treatment. TP73 can also form a regulatory network with p53 and early growth response factor 1 (Egr1), continuously activating apoptosis-related signaling pathways through feedback loops to enhance growth inhibition in tumor cells

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, suggesting that TP73 may participate in the development of endometrial cancer by forming a multidimensional regulatory network through synergy or interaction with the aforementioned proteins.The KEGG pathway enrichment analysis in this study revealed that TP73-related genes were significantly enriched in multiple tumor-related pathways, with the p53 signaling pathway showing the greatest enrichment (FDR=4.0×10⁻⁸; signal=3.5), followed by cancer-associated microRNA pathways. Additionally, pathways such as the cell cycle and platinum drug resistance pathway were significantly enriched, suggesting that TP73 may participate in endometrial cancer progression and the regulation of chemotherapy sensitivity by modulating the p53 pathway, noncoding RNAs, and the cell cycle. GO functional enrichment analysis further revealed that TP73-related genes are primarily localized in the nucleus and enriched in transcriptional regulatory complexes, with molecular functions centered on p53 binding (FDR=1.0×10⁻¹¹; signal=5.0). Biological processes were highly enriched in p53-mediated signal transduction and DNA damage response-related intrinsic apoptotic pathways. These results suggest that TP73 primarily mediates transcriptional regulation through the p53 signaling pathway, which is involved in key biological processes such as apoptosis, DNA damage repair, and the cell cycle. Notably, YAP1, a key effector of the Hippo pathway, is abnormally activated in endometrial cancer. Its interaction with TP73 constitutes a specific regulatory mechanism for the DNA damage response. Under DNA damage stress induced by chemotherapeutic agents such as cisplatin, YAP1 is phosphorylated at the Y357 site and forms a stable functional complex with TP73, specifically binding to pro-apoptotic gene promoters and activating the mitochondrial apoptotic pathway, thereby enhancing tumor cell sensitivity to DNA-damaging agents

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. Additionally, TP73 can form a multidimensional regulatory network with p53 and Egr1, continuously activating apoptotic signals through feedback loops and thereby enhancing the growth inhibitory effect on tumor cells

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.

Enrichment analysis revealed that genes related to the expression of TP73 are enriched primarily in RNA transport, proteasome activity, ECM-cytokine receptor interactions, and ribosome biogenesis. The enrichment of the ECM‒receptor interaction pathway suggested that TP73 can regulate the synthesis and remodeling of the extracellular matrix, thereby influencing tumor cell adhesion, invasion, and distant metastasis. Abnormal expression of TP73 has been confirmed to be associated with malignancies such as head and neck squamous cell carcinoma

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. Additionally, the enrichment of RNA transport and proteasome pathways reflects the multidimensional regulatory role of TP73 in the occurrence and development of endometrial cancer, which is closely associated with its known core functions and the specific biological characteristics of endometrial cancer. As a key transcriptional regulatory factor in the p53 family, TP73 performs its transcriptional regulatory functions by mediating the nucleocytoplasmic transport of RNA molecules and the precise splicing of precursor mRNA

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. The enrichment of the RNA transport pathway suggested that TP73 can regulate the posttranscriptional processing of key genes related to endometrial cancer progression (such as hormone receptor genes and cell cycle regulatory genes) through this pathway, thereby influencing the hormone sensitivity and abnormal proliferation characteristics of endometrial cancer cells. The proteasome pathway is central to intracellular protein degradation and is closely linked to the regulation of apoptosis and cell cycle progression. TP73 can bind to the HECT-type ubiquitin ligase Itch. Itch selectively binds and ubiquitinates TP73 without acting on TP53, leading to rapid proteasome-dependent degradation of TP73. Under DNA damage stress, the expression of Itch is downregulated, resulting in elevated p73 protein levels and increased activity of its corresponding functions. In summary, TP73 interacts with key molecules such as p53 and YAP1 to form a complex regulatory network that participates in the occurrence and development of endometrial cancer, remodeling of the immune microenvironment, and regulation of chemotherapy sensitivity, providing a reliable molecular mechanism explanation for the bioinformatics results of this study

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. TP73 can regulate the activity of the ubiquitin‒proteasome system through this enriched pathway, modulating the degradation of antiapoptotic proteins and cell cycle checkpoint proteins and thereby promoting apoptosis and cell cycle arrest in endometrial cancer. Moreover, the proteasome pathway is a critical therapeutic target in endometrial cancer chemotherapy. The interaction between TP73 and this pathway may also serve as an important molecular basis for regulating the sensitivity of endometrial cancer cells to proteasome inhibitors and DNA damage-inducing chemotherapeutic agents.

The remodeling of the tumor immune microenvironment is a critical factor in tumor development and treatment response and is a key component of tumor microenvironment (TME)-related carcinogenic mechanisms

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. Tumor cells can influence the process of apoptosis by modulating the tumor microenvironment, thereby promoting cancer progression and the development of treatment resistance

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. In this study, TP73 expression levels were significantly correlated with the degree of infiltration of various immune cells. The infiltration of macrophages and other cells was negatively correlated with TP73 expression, whereas the infiltration of NK CD56bright cells, eosinophils, and Th17 cells was positively correlated with TP73 expression. Previous studies have confirmed that TAp73 can suppress NF-κB pathway activity, reduce CCL2 secretion, and block the migration of monocytes into tumor-associated macrophages. Low TP73 expression is closely associated with CD163⁺ macrophage enrichment

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, suggesting that the regulatory effect of TP73 on macrophage infiltration may be conserved across tumor types. In patients with high TP73 expression, the infiltration of classical antitumor immune cells such as CD8⁺ T cells and activated NK cells significantly increased, whereas the infiltration of immune cells such as γδ T cells and M1 macrophages markedly decreased. Stromal and ESTIMATE scores also decreased significantly. Increased infiltration of CD8⁺ T cells and activated NK cells indicates enhanced immune-killing capacity in tumor tissues. The stromal score directly reflects the relative content of stromal components in tumor tissue. The low-TP73 group had a higher stromal score, indicating a richer stromal component and a relatively lower proportion of tumor cells in the tissue microenvironment. In contrast, the high-TP73 group had a reduced stromal score, suggesting that decreased stromal deposition led to a relative increase in the tumor cell proportion. This shift in the relative proportion of tumor cells to stromal components may have triggered proportional changes in immune cell infiltration in the high-TP73 group, rather than reflecting true alterations in the absolute abundance of immune cells. Such proportional effects represent a potential bias in transcriptome-based immune infiltration analyses

^26,

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. Therefore, the altered immune cell infiltration patterns in the high-TP73 group cannot be simply attributed to active recruitment or depletion of immune cells by TP73. The potential interference from proportional effects caused by differences in the stromal score must also be fully considered. This study analyzed only the infiltration characteristics of total macrophages and M1-type macrophages and did not further explore the infiltration levels of M2-type macrophages or the association between M1/M2 polarization ratios and TP73 expression. Consequently, whether TP73 participates in remodeling the immune microenvironment of endometrial cancer by regulating macrophage polarization balance rather than merely altering total cell numbers remains unclear, which is a significant limitation of this research. M1/M2 macrophage polarization is a critical aspect of tumor immune regulation. Future studies could further investigate the regulatory role and molecular mechanisms of TP73 in macrophage polarization. Additionally, analysis of the TISIDB database revealed that TP73 expression levels are closely associated with the expression of numerous immune regulatory molecules. High TP73 expression upregulates the expression of molecules such as HLA-G and NT5E while downregulating the expression of molecules such as IL10 and TGFBR1. IL10 and TGFBR1 are key molecules in typical immunosuppressive pathways, and their downregulation can inhibit the formation of an immunosuppressive microenvironment. HLA-G is a critical immune checkpoint molecule; tumor cells upregulate its expression to suppress antitumor immune responses. The specific mechanism involves interactions with immune cell surface receptors, modulating the activation states of immune cells such as T cells and natural killer (NK) cells, ultimately aiding tumor cells in evading immune surveillance

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. Therefore, TP73 can regulate immune checkpoint molecules and cytokine networks, participate in the remodeling of the endometrial cancer immune microenvironment, and provide new insights for the selection of immunotherapy targets.

Drug sensitivity analysis revealed that the expression level of TP73 can significantly affect the response of endometrial cancer patients to chemotherapeutic drugs, which is consistent with the functional characteristics of TP73 as a tumor suppressor gene in the p53 family

¹³

. Through selective promoter selection and alternative splicing mechanisms, TP73 can generate TAp73 isoforms with transcriptional activation functions and ΔNp73 isoforms with dominant-negative regulatory functions. The balance of the expression of different isoforms can directly regulate the chemotherapeutic response mechanisms of tumor cells

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. Common chemotherapeutic drugs such as cisplatin and paclitaxel have lower IC₅₀ values in patients with low TP73 expression, suggesting that these patients are more sensitive to the aforementioned drugs. Previous studies have demonstrated that TAp73 can activate the GADD45α/MKK4/JNK signaling pathway, promoting cisplatin-induced tumor cell apoptosis, whereas TP73 deficiency or functional inhibition weakens the apoptotic pathway and reduces the threshold of chemotherapeutic drug efficacy

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. Conversely, docetaxel is more effective in patients with high TP73 expression, which may be related to TAp73-mediated cell cycle arrest under high TP73 expression. This study, while exploring the association between TP73 and chemotherapy sensitivity, focused primarily on the pro-apoptotic function of TAp73 and did not fully consider the dominant negative effect of ΔNp73 and the potential impact of tumor heterogeneity on chemotherapy sensitivity. ΔNp73 can form heterodimers with TAp73, blocking the activation of its pro-apoptotic pathway, while differences in the expression ratios of TP73 isoforms induced by tumor heterogeneity may further alter the drug response patterns of tumor cells. Additionally, the results of this study revealed that the sensitivity to paclitaxel and docetaxel, two chemotherapeutic agents with similar mechanisms of action, tended to be opposite that to TP73 expression (Figure 7). This discrepancy is hypothesized to be related to the selective regulation of TP73 isoforms by the two drugs and differences in their synergistic effects on microtubule-associated signaling pathways, which require further experimental validation. Moreover, a GSCA database analysis revealed that TP73 expression levels are associated with sensitivity to multiple potential therapeutic drugs, providing clues for the screening of novel targeted agents. The results of this study suggest that targeting TP73 and its related signaling pathways is a promising novel therapeutic strategy for endometrial cancer. However, TP73 has complex isoform-specific functions and is involved in physiological processes such as apoptosis and transcriptional regulation in normal tissues. Directly targeting the overall TP73 molecule is likely to face feasibility challenges and potential toxicity risks: the TAp73 isoform possesses tumor-suppressive functions, and direct targeting may disrupt its normal physiological regulatory role, leading to weakened tumor-suppressive effects. Additionally, TP73 is relatively highly expressed in normal reproductive, hematopoietic, and other tissues, and nonspecific targeting may cause damage to normal cells, increasing treatment-related toxicity. Therefore, directly targeting TP73 is not the optimal strategy. Targeting the cancer-promoting ΔNp73 isoform of TP73 by inhibiting ΔNp73 expression or blocking its heterodimer formation with TAp73 and TP53 can restore the normal functions of tumor-suppressive isoforms while avoiding interference with these isoforms and normal tissues. Alternatively, targeting specific downstream effector molecules of TP73, such as key molecules in the RNA transport and proteasome pathways enriched in this study, as well as immune regulation-related molecules and chemotherapy sensitivity-associated GADD45α/MKK4 pathway molecules, can indirectly intervene in TP73-mediated procancer signaling through the regulation of downstream targets. This approach preserves normal physiological functions while precisely blocking tumor-related regulatory pathways.

This study is solely based on multidatabase integrated analysis and lacks experimental validation with clinical samples. Some mechanistic analyses remain at the level of bioinformatics prediction. In the future, cell experiments, animal model establishment, and clinical sample validation are needed to determine the molecular mechanisms through which TP73 regulates the development and progression of endometrial cancer. Additionally, the relationships between TP73 and the immune microenvironment as well as chemotherapy sensitivity should be explored. Furthermore, the functional differences among different TP73 isoforms and their expression characteristics in endometrial cancer have not yet been elucidated. Subsequent research could investigate the roles and regulatory networks of different isoforms to identify more specific targets for precise targeted therapy.

Although this study systematically analyzed the potential role of TP73 in endometrial cancer through various bioinformatics methods, several limitations remain. The analysis in this study was based on data from public databases, and further in vitro or in vivo experiments to validate the related conclusions are lacking. Second, the sample sources of the databases used in this study may have some selection bias, which could influence the research results. Therefore, future studies still need to integrate more clinical samples and functional experiments to further verify the specific mechanisms of TP73 in the development and progression of endometrial cancer. This study has several limitations. All analyses are based on bioinformatics mining of public databases, and no in vitro cell experiments, in vivo animal experiments, or clinical sample validations have been performed. Therefore, the conclusions drawn are merely predictive and cannot yet confirm the true biological role of TP73 in regulating the immune microenvironment and chemotherapy sensitivity in endometrial cancer. In addition, although TP73 was found to be significantly associated with the infiltration of immune cells such as macrophages and NK CD56bright, it remains unclear through which cytokines, chemokines, or immune checkpoint molecules it mediates regulation; only differential molecules are listed, and the inter-molecular interaction network and the direct/indirect regulatory relationship with TP73 have not been systematically constructed.Future plans include the collection of clinical endometrial cancer tissues and paired adjacent normal tissues to validate TP73 expression levels using qRTPCR, Western blotting, and immunohistochemistry. Endometrial cancer cell lines will be used to construct TP73 knockdown and overexpression models. Combined with CCK8, colony formation, and flow cytometry, the effects on cell proliferation and apoptosis will be assessed. Chemotherapy sensitivity will be evaluated by measuring cell IC50 values after treatment with cisplatin and docetaxel. Additionally, the expression of immune-related molecules was detected to preliminarily explore the potential mechanisms underlying the regulatory effect of TP73 on the immune microenvironment. Furthermore, combined with TISIDB analysis results and cell experiments, we will strengthen the screening of core immune molecules and the discussion of mechanisms, so as to provide a clear direction for subsequent mechanism research, thereby providing experimental evidence to support the conclusions of this study.

Conclusion

Through systematic bioinformatics analysis, this study revealed that TP73 is highly expressed in endometrial cancer and is closely associated with patient clinical characteristics, the tumor immune microenvironment, and chemotherapy drug sensitivity. TP73 may play a significant regulatory role in the pathogenesis and progression of endometrial cancer by interacting with various tumor-related proteins, modulating immune cell infiltration, and regulating signaling pathway activity. It also holds promise as a potential diagnostic biomarker and a target for precision therapy. This study provides new theoretical foundations for further exploration of the mechanistic role of TP73 in endometrial cancer. However, this study relies solely on public databases and bioinformatics predictions and has not conducted experimental research, such as in vitro cell experiments, in vivo animal experiments, or clinical sample validation, which presents certain limitations. Therefore, these conclusions are favorable and cannot confirm the actual biological functions of TP73 in regulating the immune microenvironment of endometrial cancer and chemotherapy sensitivity. In the future, qRTPCR, Western blot, and immunohistochemical experiments will be performed to validate the expression levels of TP73 in clinical endometrial cancer tissues and adjacent normal tissues; TP73 knockdown and overexpression cell models will be constructed to assess its effects on cell proliferation, apoptosis, and sensitivity to cisplatin and docetaxel, and changes in the expression of immune-related molecules will be detected to preliminarily explore its regulatory mechanisms in the tumor immune microenvironment. Subsequent studies will combine TISIDB analysis results with cell experiments to strengthen the screening of core immune molecules and the discussion of mechanisms. This study provides new theoretical foundations for further investigations into the role and mechanisms of TP73 in endometrial cancer.

References