Lung adenocarcinoma (LUAD) remains a leading cause of cancer‑related mortality, and mitochondrial proteins have been increasingly implicated in tumor progression. Coiled‑coil‑helix‑coiled‑coil‑helix domain‑containing 2 (CHCHD2) has been reported in several malignancies, yet its pan‑cancer landscape and LUAD‑specific functional relevance have not been comprehensively evaluated. In the present study, multi‑omics analyses were integrated using The Cancer Genome Atlas‑derived datasets and public resources [including Gene Expression Profiling Interactive Analysis (GEPIA) 2, CIBERSORT and CellMiner] to characterize CHCHD2 expression patterns, clinical associations, tumor microenvironment (TME) features, stemness‑related indices and drug‑response correlations across cancers, followed by experimental validation in LUAD models. CHCHD2 was found to be upregulated in multiple cancers and was correlated with advanced disease stage and poor overall survival, especially in patients with LUAD. CHCHD2 promoted cell proliferation and migration while inhibiting apoptosis. CHCHD2 knockdown reduced AKT and ERK phosphorylation and suppressed xenograft tumor growth in vivo. High CHCHD2 expression was associated with increased stemness, an immunosuppressive TME, and differential drug‑response patterns in CellMiner analyses, suggesting that CHCHD2 expression may be associated with compound‑specific sensitivity profiles. Collectively, these findings support an oncogenic role of CHCHD2 in LUAD and highlight its potential utility as a prognostic biomarker and therapeutic target.

The majority of head and neck cancers arise from the mucosal squamous epithelium of the oral cavity, pharynx and larynx, and are collectively referred to as head and neck squamous cell carcinoma (HNSCC). A multimodal standard of care is applied for case management. Primary oral cavity cancers are treated with resection followed by adjuvant cisplatin‑based chemoradiotherapy (CRT), and definitive concurrent CRT is applied for pharyngeal or laryngeal disease. In human papillomavirus‑negative patients who are medically unfit for platinum treatment, the epidermal growth factor receptor‑directed monoclonal antibody cetuximab is administered concomitantly with radiotherapy (RT). More recently, immune checkpoint inhibitors (ICIs) have redefined systemic therapy for recurrent/metastatic HNSCC, yielding durable responses and a survival benefit. In total, 65‑70% of patients present with stage III‑IVA locally advanced (LA) disease, a scenario associated with therapeutic challenges and a marked deterioration in the quality of life. Neoadjuvant therapy is designed to downstage the primary tumor, eradicate occult micrometastatic disease and enhance locoregional control before definitive surgery or RT, thus offering a rational strategy for organ preservation. Contemporary regimens integrate taxane, platinum and 5‑fluorouracil induction chemotherapy with RT, and early‑phase trials have explored the feasibility and efficacy of incorporating ICIs into neoadjuvant protocols. The present review summarizes the evolution of neoadjuvant therapy for LA HNSCC, with particular emphasis on emerging immunotherapy‑based paradigms and their potential to improve oncological and functional outcomes.

Polybromo‑1 (PBRM1) is a chromatin‑remodeling factor that is altered in intrahepatic cholangiocarcinoma (ICC). The present study examined the effects of PBRM1 knockdown on tumor‑related phenotypes and glucose metabolism in HCCC‑9810 ICC cells. The present study also evaluated the roles of aldolase, fructose‑bisphosphate A (ALDOA) and nuclear factor erythroid 2‑related factor 2 (NRF2). Publicly available ICC mutation data were analyzed descriptively. The present study evaluated HCCC‑9810 cells following PBRM1 knockdown using proliferation, colony formation, wound‑healing, Transwell, metabolic, reverse transcription‑quantitative PCR, western blotting, apoptosis and mitochondrial membrane‑potential assays. ALDOA and NRF2 perturbation experiments were used to examine their contribution to the PBRM1‑knockdown phenotype. HCCC‑9810‑derived xenografts were used for in vivo assessment. PBRM1 knockdown increased proliferation, migration and invasion in HCCC‑9810 cells and altered several glucose‑metabolism readouts. ALDOA expression also increased following PBRM1 knockdown. ALDOA silencing attenuated several metabolic and survival‑related changes. NRF2 overexpression increased ALDOA expression, whereas NRF2 knockdown reduced it. Co‑silencing NRF2 attenuated the ALDOA increase associated with PBRM1 knockdown. In xenografts, PBRM1 knockdown was associated with greater tumor growth, higher ALDOA expression and a higher Ki67 signal. PBRM1 knockdown was associated with a tumor‑promoting metabolic phenotype in HCCC‑9810 cells, with ALDOA contributing to several metabolic and survival‑related changes. NRF2 perturbation further supported an NRF2‑dependent component of ALDOA regulation in this HCCC‑9810 model; however, the upstream mechanism responsible for increased NRF2 after PBRM1 knockdown remains unresolved. These findings warrant validation in independent ICC models.

SEC31 homolog A (SEC31A) is associated with a variety of cancers. This study elucidated the role of SEC31A in gastric cancer (GC). The expression of SEC31A in GC was analyzed using western blotting and immunohistochemistry. Functional experiments were performed to detect the impact of SEC31A on GC proliferation, migration and invasion. The PI3K inhibitor LY294002 was used to explore the regulation of the biological functions by SEC31A through the PI3K/AKT/mTOR pathway in GC cells. Co‑culture of THP‑1 (human leukemia cell line of monocytic origin) and GC cells was conducted to investigate the impact of SEC31A on the M2 macrophage polarization in tumor immune microenvironment. Our investigation observed elevated expression of SEC31A in both GC tissue and cell lines. Through functional studies, suppression of SEC31A was found to decrease epithelial‑mesenchymal transition (EMT), proliferation, migration and invasion in GC cells. Overexpression of SEC31A led to activation of the PI3K/AKT/mTOR signaling cascade. The PI3K inhibitor LY294002 counteracted the increases in proliferation, migration, invasion and EMT triggered by SEC31A. Co‑culture experiments involving THP‑1 and GC cells indicated that SEC31A enhanced the recruitment and M2 polarization of macrophages via CCL5 within the GC tumor microenvironment (ME). To assess the influence of M2 macrophages on malignant behavior of GC cells, M2 macrophage‑conditioned medium (M2‑CM) was applied. M2‑CM mitigated the inhibitory effects on malignant phenotypes in GC cells following SEC31A knockdown. Moreover, diminished SEC31A expression enhanced the efficacy of anti‑PD‑1 therapy in GC models. Collectively, SEC31A promoted GC progression via activating the PI3K/AKT/mTOR pathway and facilitating CCL5‑mediated M2 polarization and recruitment of tumor‑associated macrophages. SEC31A knockdown may augment the anti‑tumor response to anti‑PD‑1 treatment in GC. These findings highlight SEC31A as a valuable prognostic indicator and potential target for immunotherapy in GC, offering novel strategies to enhance the effectiveness of anti‑PD‑1 therapy.

MicroRNAs (miRNAs or miRs) represent a class of regulatory non‑coding RNAs that control post‑transcriptional gene expression and influence multiple cancer‑associated biological processes. Among these molecules, miR‑324‑5p exhibits cancer type‑dependent functions, displaying tumor‑suppressive activity in certain types of malignancy while promoting oncogenic phenotypes in others. The molecular basis responsible for these opposing effects remains to be fully clarified. The present review summarizes evidence and integrates pan‑cancer analyses from The Cancer Genome Atlas to characterize the molecular mechanisms of miR‑324‑5p across different types of malignancies, with emphasis on experimental findings from animal models investigating tumor growth and metastasis. The clinical relevance of miR‑324‑5p, including its diagnostic, prognostic and therapeutic implications, is also discussed, together with challenges limiting clinical translation, particularly tumor‑specific delivery strategies and in vivo stability. Further elucidation of the molecular contexts governing miR‑324‑5p activity may facilitate its application in precision oncology.

Following the publication of this paper, and a corrigendum (doi: 10.3892/or.2017.6144) published in 2021 to take account of duplicated western blot data that were identified in Fig. 4D, it has subsequently come to light that flow cytometric plots featured in Fig. 2D and Transwell invasion assay data in Fig. 3B, both on p. 742, contained data that were strikingly similar to data that had already been published in articles written by different research groups at different research institutes in a number of different journals. Given that the contentious data named above had already been published prior to the receipt of this paper at Oncology Reports, the Editor has decided that this paper should now be retracted from the Journal. After contacting the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 739‑746, 2018; DOI: 10.3892/or.2017.6144].

The high mortality associated with ovarian cancer is closely linked to immune remodeling within the tumor microenvironment (TME). V‑domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, has attracted increasing attention in tumor immunology; however, its effects on follicular regulatory T (Tfr) cell function remain unclear. The present study examined VISTA expression in ovarian cancer and explored the correlation between VISTA and alterations in the AKT/MAPK pathway in Tfr‑like cells. Ovarian cancer tissues from different clinical stages and non‑malignant control tissues were analyzed by immunofluorescence, reverse transcription‑quantitative PCR and western blotting to assess VISTA expression and its association with FOXP3[+]CXCR5[+] Tfr‑like cell infiltration. Naive CD4[+] T cells were differentiated into Tfr‑like cells in vitro, and VISTA overexpression and silencing models were used to evaluate cell proliferation, cytokine secretion, and AKT/MAPK pathway activation. VISTA expression increased with ovarian cancer progression and was positively associated with Tfr‑like cell infiltration. In vitro, VISTA promoted Tfr‑like cell proliferation and the secretion of the anti‑inflammatory cytokines interleukin‑10 and transforming growth factor beta 1 while suppressing the immune effector molecules interleukin‑21 and granzyme B, accompanied by reduced AKT and extracellular signal‑regulated kinase 1/2 phosphorylation. Collectively, VISTA is upregulated in ovarian cancer and changes in VISTA expression are associated with enhanced immunosuppressive function of Tfr‑like cells as well as altered AKT/MAPK phosphorylation levels. These findings provided new insights into the regulation of the ovarian cancer TME and support further investigation of VISTA‑targeted immunotherapy.

Protein arginine methyltransferase 7 (PRMT7), the sole type III PRMT family member, catalyzes arginine monomethylation and has recently emerged as an important regulator of cancer biology. Increasing evidence indicates that PRMT7 participates in tumor initiation and progression through epigenetic regulation, transcriptional control, RNA processing and signaling pathway modulation. Dysregulated PRMT7 expression has been reported in diverse malignancies, including leukemia, breast cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, prostate cancer and gastric cancer. Functionally, PRMT7 has been implicated in epithelial‑mesenchymal transition, cancer stemness, metastasis and immune modulation, although its effects may vary depending on cellular and tumor context. The present review summarizes the structural and biochemical features of PRMT7, its mechanistic roles across different cancer types, and its potential as a therapeutic target. Recent progress in PRMT inhibitor development was also discussed, with particular emphasis on PRMT7‑selective compounds such as SGC3027, SGC8158 and JS1310, as well as the key challenges that remain for clinical translation. Elucidating the context‑specific functions and targetable vulnerabilities of PRMT7 may provide new opportunities for precision cancer therapy.

Non‑small cell lung cancer (NSCLC) is characterized by marked spatial immune heterogeneity, commonly manifested as immune‑desert, immune‑excluded and immune‑inflamed phenotypes. These phenotypes are closely associated with variable responses to immune checkpoint inhibitors (ICIs). Emerging evidence suggests that they are shaped not only by canonical immune pathways but also by mitochondrial processes that regulate immune priming, T‑cell trafficking and the maintenance of effector function. The present review summarizes how mitochondrial reactive oxygen species, mitochondrial DNA‑cGAS‑STING signaling, pathways mediated by tricarboxylic acid cycle metabolites, and non‑cell‑autonomous mitochondrial transfer may contribute to the establishment and maintenance of distinct spatial immune phenotypes in NSCLC. It is proposed that insufficient activation of innate immunity and impaired dendritic cell priming are particularly relevant to immune‑desert tumors, whereas chronic oxidative stress may reinforce barriers mediated by cancer‑associated fibroblasts (CAFs), transforming growth factor β, and the extracellular matrix in immune‑excluded tumors. By contrast, immune‑inflamed tumors may represent a state in which pre‑existing immune circuitry remains intact and tumor‑infiltrating lymphocytes retain greater mitochondrial fitness and metabolic resilience. The implications of these mechanisms for ICI sensitivity and cold‑to‑hot tumor conversion strategies were further discussed. Current evidence from human studies remains largely correlative, and prospective, spatially resolved functional studies are needed. Nevertheless, integrating mitochondrial biology with spatial immune architecture within a phenotype‑guided framework may generate testable hypotheses for future biomarker development and combination strategies.

Prostate cancer progression toward an aggressive, therapy‑resistant disease state remains a major clinical challenge, indicating a need to identify novel molecular drivers of such progression and actionable therapeutic targets. The present study analyzed the role of dynein heavy chain domain 1 (DNHD1), a previously uncharacterized regulator of malignancy, in prostate cancer. Integrative transcriptomic analyses across The Cancer Genome Atlas and independent clinical cohorts revealed that DNHD1 is markedly upregulated in advanced‑stage prostate cancer and positively correlated with increasing Gleason scores. Elevated DNHD1 expression was associated with poor overall survival and disease‑free survival, which supports its clinical relevance as a prognostic biomarker. Functional analyses demonstrated that DNHD1 promoted tumor cell proliferation, colony formation, migration and invasion in vitro. Molecular correlation modeling and pathway analyses revealed histone deacetylase 6 (HDAC6) as a key downstream effector of DNHD1. DNHD1 expression was positively correlated with and regulated HDAC6 expression in clinical datasets. Gain‑of‑function and loss‑of‑function experiments further revealed that HDAC6 is required for DNHD1‑mediated oncogenic phenotypes in prostate cancer, positioning HDAC6 as a functional mediator downstream of DNHD1. The DNHD1‑HDAC6 axis was associated with cilium assembly‑related pathways, suggesting a previously unrecognized association between ciliary regulation and prostate cancer progression. HDAC6 inhibition with tubastatin A effectively suppressed DNHD1‑driven tumor growth and motility, as well as increased acetylated α‑tubulin and decreased androgen receptor signaling. These findings indicated a potential therapeutic vulnerability within the DNHD1‑HDAC6 axis. They implied that in prostate cancer, the DNHD1‑HDAC6 axis, a novel regulatory pathway, promotes aggressiveness and that HDAC6 is a targetable mediator of DNHD1‑driven malignancy. This axis can be considered a prognostic indicator and mechanistic foundation for developing targeted therapeutic strategies for advanced prostate cancer.

Lung squamous cell carcinoma (LUSC) is an aggressive malignancy with a poor prognosis. Given the association between mitochondrial dysregulation and LUSC, the aim of the present study was to identify mitochondrial unfolded protein response (UPR[mt])‑related candidate genes associated with LUSC and to explore their potential functional relevance. In the present study, differential expression, univariate Cox and survival analyses were combined to identify a UPR[mt]‑associated key gene in LUSC. Gene set enrichment analysis was then performed, and overexpression (OE) and knockdown cell lines were used to clarify its function using western blotting, Cell Counting Kit‑8, colony formation and Transwell[®] invasion assays. Using bioinformatics tools and a review of the literature, PTEN‑induced kinase 1 (PINK1) was singled out as a key gene in LUSC samples. Elevated PINK1 expression was associated with worse survival outcomes. A total of 117 pathways were enriched by PINK1, with the top 5 including 'focal adhesion' and 'mitogen‑activated protein kinase signaling pathway'. Using experimental analysis, it was observed that PINK1 significantly enhanced the proliferative, migratory, invasive and colony forming abilities of tumor cells, thereby exacerbating LUSC. Furthermore, these enhancements were diminished by the application of focal adhesion kinase (FAK) inhibitor. It was also noted that the expression levels of protein kinase B (AKT), p‑AKT, Ras homolog family member A (RhoA) and vinculin were all elevated in OE‑PINK1 cells. Collectively, these findings indicated that PINK1 exerted its influence on LUSC through the FAK/AKT/RhoA/vinculin pathway. The present study identified PINK1 as a key gene in LUSC, exerting its influence through the FAK/AKT/RhoA/vinculin pathway, thereby presenting a potential novel therapeutic target for the treatment of LUSC in the future.

Following the publication of the above article, a concerned reader has contacted the Editorial Office to draw attention to the fact that there appeared to be discrepancies between the numbers of patients reported with low‑ or high‑ZNF703 expression in Fig. 3 on p. 1074: Fig. 3A reported 70 patients with low ZNF703 expression and 68 patients with high expression; however, the stage‑stratified Kaplan‑Meier curves showed the following: In Fig. 3B, stages I‑IIIA: 57 low‑expression and 20 high‑expression patients, and in Fig. 3C, stages IIIB‑IV: 20 low‑expression and 41 high‑expression patients (and so 70 vs. 68 patients in Fig. 3A, and 77 vs. 61 patients in Fig. 3B and C). In addition, the AJCC stage‑specific counts reported in Table I also showed internal inconsistencies in terms of the overall numbers of low‑ and high‑expression patients, and finally, an additional discrepancy was noted for the definition of the high expression group: The Materials and methods section stated that an immunohistochemical score of ≥6 was classified as high expression, whereas the Table I column heading defined high expression as '>6'. To clarify these apparent discrepancies, the authors should resolve the following: i) provide the actual numbers of low‑ and high‑expression patients in each AJCC stage group; ii) clarify whether the cutoff used for the Kaplan‑Meier analyses was ≥6 or >6; iii) provide the exact patient numbers used to generate Fig. 3A, B and C; and iv) clarify whether the counts, totals and percentages in Table I require correction. Finally, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that, regarding the wound healing assay data shown in Fig. 6A on p. 1076, the '24 h / Control' and '24 h / NC siRNA' panels showed an overlapping section of data, such that data which were intended to show the results of experiments performed under different conditions had apparently been derived from the same original source. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomalies in the description of the data, and the incorrect assembly of data in Fig. 6, in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of this potential issue concerning the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 32: 1071‑1077, 2014; DOI: 10.3892/or.2014.3313].

Cervical cancer is a malignant tumor that threatens women's health and radiotherapy represents a major therapeutic approach for its treatment; however, radioresistance frequently leads to treatment failure. The present study aimed to investigate whether loperamide (LOP), a µ‑opioid receptor agonist commonly used as an antidiarrheal agent, could enhance the radiosensitivity of cervical cancer cells by regulating ferroptosis. A Cell Counting Kit‑8 assay was used to evaluate the cytotoxicity of LOP in SiHa and HeLa cells, and EdU and colony formation assays were performed to assess cell proliferation. In addition, wound‑healing and Transwell assays were performed to detect cell migration. Flow cytometry was applied to measure cell apoptosis and intracellular reactive oxygen species (ROS) levels, and colorimetric assays were used to determine malondialdehyde (MDA) and glutathione (GSH) contents. The mRNA and protein expression levels of the ferroptosis‑related markers GSH peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were analyzed using reverse transcription‑quantitative PCR and western blotting. The results showed that LOP significantly inhibited the viability of SiHa and HeLa cells, and exerted a synergistic effect with radiotherapy (combination index <1) to suppress cell proliferation and migration. Combined treatment with LOP and radiotherapy markedly increased apoptosis and ROS accumulation, elevated MDA levels and reduced GSH levels. Moreover, the combination treatment significantly downregulated the expression of GPX4 and SLC7A11. These findings indicated that LOP enhances the radiosensitivity of cervical cancer cells, with ferroptosis induction via inhibition of the GPX4/SLC7A11 axis as a contributing mechanism. Both apoptosis and ferroptosis were induced by the combination treatment, suggesting that the radiosensitizing effect may involve multiple cell death pathways. These observations provide a basis for further investigation into LOP as a potential radiosensitizing agent in cervical cancer.

Following the publication of the above article, a concerned author drew to the authors' attention that, regarding the cell migration assay experiments shown in Fig. 4 on p. 1099, Fig. 4B and C, showing the results of the 'NC' and 'Mock' experiments, contained an overlapping section of data, suggesting that these data panels were derived from the same original source where different experiments were intended to have been portrayed. The authors have been contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of this potential issue concerning the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 31: 1096‑1102, 2014; DOI: 10.3892/or.2014.2971].

The present study aimed to characterize the expression pattern and biological function of sphingosine‑1‑phosphate phosphatase 1 (SGPP1) in esophageal squamous cell carcinoma (ESCC), investigate its potential molecular regulatory mechanisms, and evaluate its clinical value as a prognostic biomarker and therapeutic target. SGPP1 expression in ESCC cell lines was assessed by reverse transcription‑quantitative PCR and western blotting. Models of SGPP1 overexpression in KYSE150 cells and SGPP1 knockdown in ECA109 cells were established. 5‑Ethynyl‑2'‑deoxyuridine, Cell Counting Kit‑8, colony formation, terminal deoxynucleotidyl transferase dUTP nick‑end labeling, wound healing and Transwell assays were performed to systematically analyze the effects of SGPP1 on ESCC cell proliferation, apoptosis, migration and invasion. The Cancer Genome Atlas‑ESCC data were integrated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, gene set enrichment analysis and UpSet plotting to identify key downstream pathways and candidate target genes. SGPP1 protein expression was evaluated by immunohistochemistry in tumor tissues from 68 patients with ESCC, and Cox regression analysis was used to assess its association with patient prognosis. The results demonstrated that SGPP1 expression varied markedly among ESCC cell lines, with low expression in KYSE150 cells and high expression in ECA109 cells. SGPP1 overexpression significantly inhibited ESCC cell proliferation, migration and invasion, and increased apoptosis‑associated DNA fragmentation, whereas SGPP1 knockdown produced the opposite effects. Mechanistically, the data suggested that SGPP1 modulates extracellular matrix remodeling and xenobiotic metabolism, potentially through negative regulation of UGT1A9 and UGT2B28 expression. Clinically, low SGPP1 expression was an independent risk factor for poor prognosis in patients with ESCC (HR=6.016, 95% CI: 3.143‑11.513, P<0.001), and the overall survival was significantly longer in the high‑expression group than in the low‑expression group (P<0.001). In conclusion, SGPP1 functions as a tumor suppressor gene in ESCC and may inhibit tumor progression by regulating UGT1A9/UGT2B28‑mediated metabolic pathways. SGPP1 may therefore serve as a prognostic biomarker and a potential therapeutic target in ESCC.