Biomarker In Many Cancers Research Articles

Ki-67 AS A PREDICTING FACTOR OF NASOPHARYNGEAL, BREAST, AND CERVICAL CANCER: A LITERATURE REVIEW

Background: Although the exact role remains unknown, Ki-67 is vital in cell division. Ki-67 is a nuclear nonhistone protein present in all active phases of the cell cycle. It has the potential to predict the prognosis of responsiveness to radiotherapy, chemotherapy, or endocrine therapy, estimate residual risk, and predict recurrence in many types of cancer, including nasopharyngeal cancer (NPC), breast cancer (BC), and cervical cancer (CX), and be a marker for treatment efficacy. We want to review the efficacy of Ki-67 as a predicting factor for three types of cancer, including NPC, breast, and cervical cancer, from several pieces of literature. Materials and Methods: We are conducting a literature review to describe the role of Ki-67 as a predicting factor in NPC, BC, and CX. Results: Pretreatment Ki-67 is used as an independent prognostic marker in NPC, and elevated values are associated with poor prognosis. High Ki-67 expression may indicate poorer recurrence-free survival and overall survival. A high Ki-67 index significantly correlated with adverse prognostic factors. Conclusion: A high expression of Ki-67 in NPC, breast cancer, and cervical cancer is associated with poor prognosis, poorer recurrence, and overall survival rates. Ki-67 can be considered as a valuable biomarker of many cancers. Keywords: Radiotherapy, Ki-67, nasopharyngeal cancer, breast cancer, cervical cancer

Tumour-specific phosphorylation of serine 419 drives alpha-enolase (ENO1) nuclear export in triple negative breast cancer progression

BackgroundThe glycolytic enzyme alpha-enolase is a known biomarker of many cancers and involved in tumorigenic functions unrelated to its key role in glycolysis. Here, we show that expression of alpha-enolase correlates with subcellular localisation and tumorigenic status in the MCF10 triple negative breast cancer isogenic tumour progression model, where non-tumour cells show diffuse nucleocytoplasmic localisation of alpha-enolase, whereas tumorigenic cells show a predominantly cytoplasmic localisation. Alpha-enolase nucleocytoplasmic localisation may be regulated by tumour cell-specific phosphorylation at S419, previously reported in pancreatic cancer.ResultsHere we show ENO1 phosphorylation can also be observed in triple negative breast cancer patient samples and MCF10 tumour progression cell models. Furthermore, prevention of alpha-enolase-S419 phosphorylation by point mutation or a casein kinase-1 specific inhibitor D4476, induced tumour-specific nuclear accumulation of alpha-enolase, implicating S419 phosphorylation and casein kinase-1 in regulating subcellular localisation in tumour cell-specific fashion. Strikingly, alpha-enolase nuclear accumulation was induced in tumour cells by treatment with the specific exportin-1-mediated nuclear export inhibitor Leptomycin B. This suggests that S419 phosphorylation in tumour cells regulates alpha-enolase subcellular localisation by inducing its exportin-1-mediated nuclear export. Finally, as a first step to analyse the functional consequences of increased cytoplasmic alpha-enolase in tumour cells, we determined the alpha-enolase interactome in the absence/presence of D4476 treatment, with results suggesting clear differences with respect to interaction with cytoskeleton regulating proteins.ConclusionsThe results suggest for the first time that tumour-specific S419 phosphorylation may contribute integrally to alpha-enolase cytoplasmic localisation, to facilitate alpha-enolase’s role in modulating cytoskeletal organisation in triple negative breast cancer. This new information may be used for development of triple negative breast cancer specific therapeutics that target alpha-enolase.

A target-triggered fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular telomerase activity

Telomerase (TE) is a promising diagnostic and prognostic biomarker for many cancers. Quantification of TE activity in living cells is of great significance in biomedical and clinical research. Conventional fluorescence-based sensors for quantification of intracellular TE may suffer from problems of fast photobleaching and auto-fluorescence of some endogenous molecules, and hence are liable to produce false negative or positive results. To address this issue, a fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular TE was designed by functionalizing a bimetallic Au@Ag nanostructure with 4-p-mercaptobenzoic acid (internal standard SERS tag) and a DNA hybrid complex consisted of a telomerase primer strand and its partially complimentary strand modified with Rhodamine 6G. The bimetallic Au@Ag nanostructure serves as an excellent SERS-enhancing and fluorescence-quenching substrate. Intracellular TE will trigger the extension of the primer strand and cause the shedding of Rhodamine 6G-modified complimentary strand from the nano-system through intramolecular DNA strand displacement, resulting in the recovery of the fluorescence of Rhodamine 6G and decrease in its SERS signal. Both the fluorescence of R6G and the ratio between the SERS signals of 4-p-mercaptobenzoic acid and Rhodamine 6G can be used for in situ imaging of intracellular TE. Experimental results showed that the proposed nano-system was featured with low background, excellent cell internalization efficiency, good biocompatibility, high sensitivity, good selectivity, and robustness to false positive results. It can be used to distinguish cancer cells from normal ones, identify different types of cancer cells, as well as perform absolute quantification of intracellular TE, which endows it with great potential in clinical diagnosis, target therapy and prognosis of cancer patients.

Antimicrobial potential of quaternary phosphonium salt compounds: a review.

Given that mitochondrial dysregulation is a biomarker of many cancers, cationic quaternary phosphonium salt (QPS) conjugation is a widely utilized strategy for anticancer drug design. QPS-conjugated compounds exhibit greater cell permeation and accumulation in negatively charged mitochondria, and thus, show enhanced activity. Phylogenetic similarities between mitochondria and bacteria have provided a rationale for exploring the antibacterial properties of mitochondria-targeted compounds. Additionally, due to the importance of mitochondria in the survival of pathogenic microbes, including fungi and parasites, this strategy can be extended to these organisms as well. This review examines recent literature on the antimicrobial activities of various QPS-conjugated compounds and provides future directions for exploring the medicinal chemistry of these compounds.

In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry.

Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. We use this strategy to monitor O-GlcNAc within hepatic VX2 tumor tissue. We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression.

Prognostic value and immunological role of PTPN21 in pan-cancer analysis.

At present, cancer remains a persistent public health challenge facing the whole world. Studies have found that PTPN21 is associated with the development of cancer. However, the prognostic potential of PTPN21 in pan-cancer remains unclear. In this work, we aimed to analyze the expression and prognostic value of PTPN21 in pan-cancer and to further study the relationship between PTPN21 and immune infiltration. TCGA and GEO data were used for expression and survival analysis. Genetic alterations in PTPN21 from TCGA cancer were studied in cBioPortal. TIMER2 was used to evaluate the correlation between PTPN21 expression and immune infiltration. The R packages "ggplot2" and "clusterProfiler" were used for GO and KEGG analysis. PTPN21 was found to be a valuable diagnostic biomarker in multiple cancers, including bladder urothelial carcinoma (BLCA), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and lung squamous cell carcinoma (LUSC). In addition, we observed that PTPN21 expression was associated with a variety of tumor mutations. Our results indicated a correlation between PTPN21 expression and immune infiltration. Enrichment analysis showed that PTPN21 was mainly involved in the regulation of neuroactive ligand-receptor interaction. Our study showed that PTPN21 expression is associated with clinical prognosis, mutation, and immune infiltration of tumors. PTPN21 may be a potential biomarker for many cancers, especially in KIRC.

Pan-Cancer Analysis of TLE3 Revealed Its Value in Tumor Microenvironment and Prognosis.

Transducin-like enhancer of split 3 (TLE3), a member of the TLE gene family, is related to tumor genesis and progression. However, whether TLE3 played a crucial role in the whole pan-cancer remained unknown. Comprehensive analysis of TCGA, GEO, and GTEx data with an online tool, and R language was performed to explore the relationship of TLE3 expression between prognosis, gene mutation, protein phosphorylation, DNA methylation, tumor microenvironment, and related pathways in 33 tumors. TLE3 was high-expressed in most tumors, and TLE3 expression and the prognosis of some tumor types were significantly correlated. The level of TLE3 expression in 33 cancer types was closely associated with DNA methylation. High-level phosphorylation sites of Tle3, such as S267 and S217, may promote cancers. In terms of the tumor microenvironment, TLE3 affected a wide variety of cancers, especially PRAD and LIHC, and TLE3 may act on them via immune-related pathways. The current work provided the first comprehensive investigation of TLE3 in a pan-cancer study, highlighting the role of TLE3 in the tumor immune microenvironment, and also determined the potential of TLE3 as a prognostic, immunotherapy response, and diagnostic biomarker in many cancers. However, the present results were preliminary and required further validation as this study was based on bioinformatics analyses.

700P Prognostic miRNA signature score in patients with HNSCC

MicroRNAs (miRNAs) have been evaluated as a potential biomarker in many cancers, including HNSCC. Therefore, we aimed to identify a prognostic miRNA signature score from The Cancer Genome Atlas (TCGA) database and further validated it in our HNSCC cohort.

JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer.

BackgroundJMJD8 has recently been identified as a cancer-related gene, but current studies provide limited information. We aimed to clarify its roles and the potential mechanisms in pan-cancer.MethodsPan-cancer bulk sequencing data and online web tools were applied to analyze JMJD8’s correlations with prognosis, genome instability, cancer stemness, DNA repair, and immune infiltration. Moreover, single-cell datasets, SpatialDB database, and multiple fluorescence staining were used to validate the association between JMJD8 expression and M2 macrophages. Further, we utilized ROCplotter and cMap web tool to analyze the therapeutic responses and screened JMJD8-targeted compounds, respectively, and we used AlphaFold2 and Discovery Studio to conduct JMJD8 homology modeling and molecular docking.ResultsWe first noticed that JMJD8 was an oncogene in many cancer types. High JMJD8 was associated with lower genome stability. We then found that high JMJD8 correlated with high expression of mismatch repair genes, stemness, homologous repair gene signature in more than 9 cancers. ESTIMATE and cytokine analyses results presented JMJD8’s association with immunosuppression. Also, immune checkpoint CD276 was positively relevant to JMJD8. Subsequently, we validated JMJD8 as the M2 macrophage marker and showed its connection with other immunosuppressive cells and CD8+ T-cell depression. Finally, potential JMJD8-targeted drugs were screened out and docked to JMJD8 protein.ConclusionWe found that JMJD8 was a novel oncogene, and it correlated with immunosuppression and DNA repair. JMJD8 was highly associated with immune checkpoint CD276 and was an M2 macrophage biomarker in many cancers. This study will reveal JMJD8’s roles in pan-cancer and its potential as a novel therapeutic target.

Upregulation of Centromere Proteins as Potential Biomarkers for Esophageal Squamous Cell Carcinoma Diagnosis and Prognosis.

Esophageal squamous cell carcinoma (ESCC) has a high incidence and low survival rate, necessitating the identification of novel specific biomarkers. Centromere-associated proteins (CENPs) have been reported to be biomarkers for many cancers, but their roles in ESCC have seldom been investigated. Here, the potential clinical roles of CENPs in ESCC patients were demonstrated by a systematic bioinformatics analysis. Most CENP-encoding genes were differentially expressed between tumor and normal tissues. CENPA, CENPE, CENPF, CENPI, CENPM, CENPN, CENPQ, and CENPR were upregulated universally in the three datasets. Survival analysis demonstrated that high expression of CENPE and CENPQ was positively correlated with the outcomes of ESCC patients. The CENPE-based forecast model was more accurate than the tumor-node-metastasis (TNM) staging-based model, which was classified as stage I/II vs. III/IV. More importantly, the forecast model based on the commonly upregulated CENPs exhibited a much higher area under the curve (AUC) value (0.855) than the currently known TTL, ZNF750, AC016205.1, and BOLA3 biomarkers. The nomogram model integrating the CENPs, TNM stage, and sex was highly accurate in the prognosis of ESCC patients (AUC = 0.906). Besides, gene set enrichment analysis (GSEA) demonstrated that CENPE expression is significantly correlated with cell cycle, G2/M checkpoint, mitotic spindle, p53, etc. Finally, in validation experiments, we also found that CENPE and CENPQ were significantly overexpressed in esophageal cancer cells. Taken together, these results clearly suggest that CENPs are clinically promising diagnostic and prognostic biomarkers for ESCC patients.

SPR Analysis of SUMO-Murine Rap1-Interacting Factor 1 C-Terminal Domain Interaction with G4.

One of the advantages of surface plasmon resonance is its sensitivity and real-time analyses performed by this method. These characteristics allow us to further investigate the interactions of challenging proteins like Rap1-interacting factor 1 (Rif1). Rif1 is a crucial protein responsible for regulating different cellular processes including DNA replication, repair, and transcription. Mammalian Rif1 is yet to be fully characterized, partly because it is predicted to be intrinsically disordered for a large portion of its polypeptide. This protein has recently been the target of research as a potential biomarker in many cancers. Therefore, finding its most potent interacting partner is of utmost importance. Previous studies showed Rif1’s affinity towards structured DNAs and amongst them, T6G24 was superior. Recent studies have shown mouse Rif1 (muRif1) C-terminal domain’s (CTD) role in binding to G-quadruplexes (G4). There were many concerns in investigating the Rif1 and G4 interaction, which can be minimized using SPR. Therefore, for the first time, we have assessed its binding with G4 at nano-molar concentrations with SPR which seems to be crucial for its binding analyses. Our results indicate that muRif1-CTD has a high affinity for this G4 sequence as it shows a very low KD (6 ± 1 nM).

A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR

d-2-Hydroxyglutarate (d-2-HG) is a metabolite involved in many physiological metabolic processes. When d-2-HG is aberrantly accumulated due to mutations in isocitrate dehydrogenase or d-2-HG dehydrogenase, it functions in a pro-oncogenic manner and is thus considered a therapeutic target and biomarker in many cancers. In this study, DhdR from Achromobacter denitrificans NBRC 15125 is identified as an allosteric transcriptional factor that negatively regulates d-2-HG dehydrogenase expression and responds to the presence of d-2-HG. Based on the allosteric effect of DhdR, a d-2-HG biosensor is developed by combining DhdR with amplified luminescent proximity homogeneous assay (AlphaScreen) technology. The biosensor is able to detect d-2-HG in serum, urine, and cell culture medium with high specificity and sensitivity. Additionally, this biosensor is used to identify the role of d-2-HG metabolism in lipopolysaccharide biosynthesis of Pseudomonas aeruginosa, demonstrating its broad usages.

Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA.

Circulating tumor DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-Seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-Seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the parts-per-million range in patient samples. We profiled 678 specimens from 213 patients with B-cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B-cell lymphoma. In patients with undetectable ctDNA by CAPP-Seq after two cycles of therapy, an additional 25% have ctDNA detectable by PhasED-Seq and have worse outcomes. Finally, we demonstrate the application of PhasED-Seq to solid tumors.

Analysis of the Prognostic Value and Potential Molecular Mechanisms of TREM-1 Overexpression in Papillary Thyroid Cancer via Bioinformatics Methods.

BackgroundTriggering receptor expressed on myeloid cells-1 (TREM-1) has been reported as a biomarker in many cancers. However, the biological function of TREM-1 in papillary thyroid carcinoma (PTC) remains unknown.MethodsWe obtained TREM-1 expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and TREM-1 methylation analysis were performed via LinkedOmics. The correlations between TREM-1 and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of TREM-1 expression with pan-cancer overall survival via Gene Expression Profiling Interactive Analysis (GEPIA).Results TREM-1 has lower methylation levels and higher expression levels in PTC tissues compared to normal tissues. TREM-1 expression is significantly associated with poor prognosis, advanced T classification, advanced N classification, and an increased incidence of BRCA2 and BRAF mutations. Genes coexpressed with TREM-1 primarily participate in immune-related pathways. TREM-1 expression is positively correlated with immune infiltration, tumor progression and poor overall survival across cancers.ConclusionsTREM-1 is a good prognostic and diagnostic biomarker in PTC. TREM-1 may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of TREM-1 expression and biological function. Additionally, TREM-1 has broad prognostic value in a pan-cancer cohort.

Comparative modelling unravels the structural features of eukaryotic TCTP implicated in its multifunctional properties: an in silico approach.

Comparative modelling helps compare the structure and functions of a given protein, to track the path of its origin and evolution and also guide in structure-based drug discovery. Presently, this has been applied for modelling the tertiary structure of highly conserved eukaryotic TCTP (translationally controlled tumour protein) which is involved in a plethora of functions during growth and development and also acts as a biomarker for many cancers like lung, breast, and prostate cancer. The modelled TCTP structures of different organisms belonging to the eukaryotic group showed similar spatial arrangement of structural units except loops and similar patterns of root mean square deviation (RMSD), root mean square fluctuation, and radius of gyration (Rg) inspected through molecular dynamics simulations. Essential dynamics (ED) analyses revealed different domains that exhibited different motions for the assistance in its multifunctional properties. Construction of a free-energy landscape (FEL) based on Rg versus RMSD was employed to characterize the folding behaviours of structures and observe that all proteins had nearly similar conformation and topologies, indicating common thermodynamic/kinetic pathways. A physico-chemical interaction study demonstrated the helices and sheets were well stabilized with ample amounts of bonding compared to turns or loops and charged residues were more accessible to solvent molecules. Hence, the current study reveals the important structural features of TCTP that aid in diverse functions in a wide range of organisms, thus extending our knowledge of TCTP and also providing a venue for designing the potent inhibitors against it.

Proteolysis-Responsive Rolling Circle Transcription Assay Enabling Femtomolar Sensitivity Detection of a Target Protease Biomarker.

Proteases play crucial roles in the malignant progression of tumor and thus have been regarded as biomarkers for many cancers. Although protease assays such as immunoassays and fluorogenic substrate probes have been developed, it remains challenging for them to give consideration to both sensitivity and accuracy. Here, we describe a proteolysis-responsive rolling circle transcription assay (PRCTA) for the ultrasensitive and accurate detection of protease activities by the rational integration of a protease-responsive RNA polymerase and rolling circle transcription. Taking cancer biomarker matrix metalloproteinase-2 (MMP-2) as the model, the PRCTA, which can transduce and amplify each proteolysis event catalyzed by MMP-2 into the output of multiple tandem fluorescent RNAs by in vitro transcription, is constructed for the sensitive analysis of MMP-2 activities. Such a rational integration greatly enhances the signal gain in PRCTA, and it enables the limit of detection of MMP-2 as low as 3 fM. The feasibility of PRCTA has been validated by the sensitive analysis of cellular MMP-2 activities of different cell lines with good accuracy, and the readout can be readily visualized by a fluorescence imaging system. Therefore, PRCTA has achieved the detection of target protease biomarkers with femtomolar sensitivity, exhibiting promising potential in biomedicine research and cancer diagnosis.

Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods

BackgroundInterleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined.MethodsWe obtained IL1RN expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and IL1RN methylation analysis were performed via LinkedOmics. The correlations between IL1RN and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of IL1RN expression with pancancer overall survival (OS) via Gene Expression Profiling Interactive Analysis (GEPIA).ResultsIL1RN showed higher expression levels and lower methylation levels in PTC tissues than in normal tissues. Higher IL1RN expression was significantly associated with shorter progression-free survival (PFS), advanced tumor stage, tumor metastasis, increased incidence of BRAF mutations, and decreased incidence of N-RAS and H-RAS mutations. Genes coexpressed with IL1RN participate primarily in immune-related pathways. IL1RN expression positively correlated with immune infiltration, tumor progression and poor OS for all cancers.ConclusionsIL1RN is a good prognostic and diagnostic biomarker for PTC. IL1RN may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of IL1RN expression and biological function. Additionally, IL1RN was shown to have broad prognostic value in a pancancer cohort.

Bioinformatics analysis of the clinical value and potential mechanisms of AHNAK2 in papillary thyroid carcinoma.

Background: AHNAK2 has been recently reported as a biomarker in many cancers. However, a systematic investigation of AHNAK2 in papillary thyroid carcinoma (PTC) has not been conducted.Results: AHNAK2 is overexpressed in PTC tissues and could be an independent prognostic factor. AHNAK2 expression was significantly high in patients with advanced stage, advanced T classification, lymph node metastasis, increased BRAF mutations and decreased RAS mutations. Cell adhesion-, cell junction-, and immune-related pathways were the most frequently noted in gene set enrichment analysis. AHNAK2 expression in PTC was positively correlated with immune infiltration and negatively correlated with AHNAK2 methylation. AHNAK2 expression was significantly positively correlated with tumor progression and poor overall survival (OS) in pan-cancer patients.Conclusions: AHNAK2 is a good biomarker for the diagnosis and prognosis of PTC. AHNAK2 may promote thyroid cancer progression through cell adhesion-, cell junction-, and immune-related pathways. Methylation may act as an upstream regulator to inhibit the expression and biological function of AHNAK2. Additionally, AHNAK2 has broad prognostic value in pan-cancer.Methods: Based on The Cancer Genome Atlas (TCGA) data, we screened AHNAK2-related genes through weighted gene coexpression network analysis and explored the clinical value and the potential mechanism of AHNAK2 in PTC by multiomics analysis.

Targeting histone demethylase KDM5B for cancer treatment.

KDM5B (Lysine-Specific Demethylase 5B) erases the methyl group from H3K4me2/3, which performs wide regulatory effects on chromatin structure, and represses the transcriptional function of genes. KDM5B functions as an oncogene and associates with human cancers closely. Targeting KDM5B has been a promising direction for curing cancer since the emergence of potent KDM5B inhibitor CPI-455. In this area, most reported KDM5B inhibitors are Fe (Ⅱ) chelators, which also compete with the cofactor 2-OG in the active pockets. Besides, Some KDM5B inhibitors have been identified through high throughput screening or biochemical screening. In this reviewing article, we summarized the pioneering progress in KDM5B to provide a comprehensive realization, including crystal structure, transcriptional regulation function, cancer-related functions, development of inhibitors, and SAR studies. We hope to provide a comprehensive overview of KDM5B and the development of KDM5B inhibitors.

Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC

Trop2 is an intracellular calcium signal transducer and a prognostic biomarker in many cancers. P16 is a cell cycle gene that negatively regulates cell proliferation and division in most human cancers. Oral squamous cell carcinoma (OSCC) is a common malignant tumor subgroup of head and neck squamous cell carcinoma worldwide. Both Ca2+-dependent and cell cycle signaling pathways play vital roles in OSCC, although the molecular mechanisms remain to be elucidated. We aimed to examine the function of Trop2 and P16 in regulating intracellular calcium ions and the cell cycle in OSCC cell lines. Furtherly, the mRNA and protein expression levels of Trop2 and P16 in OSCC tissue samples were assessed, and their function was evaluated as potential clinical prognostic biomarkers. Trop2 promoted intracellular calcium ion release in OSCC and induced S phase of the cell cycle. Moreover, Trop2-mediated Ca2+ inhibited P16 expression through the AMP-activated protein kinase pathway in OSCC. Interestingly, P16 overexpression could not reverse these phenomena in vitro. We also demonstrated that human OSCC tissues showed high Trop2 mRNA and protein expression, and Trop2+/P16− expression is an independent prognostic marker for OSCC patients. Our data suggest that Trop2+/P16− may be a valuable prognostic marker for OSCC and that Trop2 inhibits P16 expression and induces S phase by promoting intracellular calcium release in OSCC.