Anticancer research最新文献

Background/aim: Pancreatic cancer has a poor prognosis, with a 5-year survival rate of only 9%. Thus, there is an urgent need to develop effective cancer therapeutics for this disease. It is expected that nucleic acid therapeutics will be a next-generation cancer treatment. We previously reported that MIRTX - a complementary strand of miR-29b-1-5p (the passenger sequence of miR-29b) - exerts strong anti-tumor effects in colorectal cancer cells. Here we investigated the anti-tumor effects of MIRTX, compared to those of the guide sequence of miR-29b (miR-29b-3p), in pancreatic cancer cells.

Materials and methods: We evaluated how treatment with MIRTX and miR-29b-3p affected cell proliferation, cell cycle, apoptosis, and invasion in pancreatic cancer cell lines (Panc-1, SUIT-2, and BxPC-3). We also performed RNA-seq and in silico analyses to explore novel target genes of MIRTX.

Results: Compared to miR-29b-3p, MIRTX strongly suppressed cell proliferation and invasion, delayed cell cycle progression, and induced apoptosis in pancreatic cancer cells. RNA-seq and in silico prediction identified the genes encoding cyclin A2, cyclin B2, and NCAPD3 as potential candidate targets of MIRTX.

Conclusion: MIRTX is a potential therapeutic miRNA in pancreatic cancer cells.

Background/aim: Predicting programmed death-ligand 1 (PD-L1) expression in resectable lung cancer cases is highly significant for establishing treatment strategies. Although there were differences in tumor characteristics between central and peripheral lesions in non-small cell lung cancer (NSCLC), the relationship between tumor location and PD-L1 expression status has not been examined. We investigated the relationship between clinical background factors, including tumor location, and PD-L1 expression status.

Patients and methods: A total of 245 NSCLC patients whose tumors were measuring 3 cm or less in diameter and had a consolidation tumor ratio (CTR) <0.5 were included in this study. A tumor was classified as peripheral if its location was in the outer one-third of the computed tomography horizontal section, and as central otherwise. PD-L1 immunohistochemistry was performed using 22C3 antibody. PD-L1 expression status were categorized as negative [PD-L1 tumor proportion score (TPS) <1%] and as positive (PD-L1 TPS ≥1%).

Results: Statistically significant differences were identified in CTR (p=0.006), histology type (p<0.001) and tumor location (p=0.036) according to the PD-L1 expression status. A greater proportion of patients with a smoking history were observed in the PD-L1 expression positive group (p=0.076). Multivariate analysis revealed 0.94< CTR (p=0.033), non-adenocarcinoma (p=0.018) and central lesion (p=0.034) were independent predictive factors for positive PD-L1 expression status. A predictive scoring system incorporating these three factors demonstrated a stepwise increase in PD-L1 positivity with higher scores.

Conclusion: PD-L1 expression status significantly correlated with CTR, histological type and tumor location. This is the first report demonstrating a significant correlation between PD-L1 expression and tumor location in NSCLC. We believe that differences in the cancer microenvironment based on tumor location influence PD-L1 expression status in cancer cells.

Background/aim: Lymphovascular invasion (LVI) is a strong prognostic factor associated with poor survival outcomes in breast cancer. However, the clinical benefit of postmastectomy radiotherapy (PMRT) for early-stage disease remains uncertain. This study aimed to evaluate PMRT efficacy and related prognostic factors in real-world settings.

Patients and methods: We retrospectively analyzed 322 postoperative breast cancer patients with pathologically confirmed LVI who received radiotherapy (RT) between October 2017 and July 2020. Patients were categorized into two groups: Group A (pT1-2N1M0, n=273), who underwent modified radical mastectomy (MRM) with or without adjuvant RT; and Group B [stage II, ypN0 after neoadjuvant chemotherapy (NAC) and surgery, with or without adjuvant RT, n=49]. Intergroup differences were assessed using the chi-squared test, and Kaplan-Meier analysis estimated local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and distant DFS (DDFS).

Results: Group A: Patients who received adjuvant RT had significantly improved 5-year LRFS (94.4% vs. 85.5%, HR=0.359, 95% CI=0.147-0.879; p<0.05) and DFS (88.9% vs. 78.8%, HR=0.488, 95% CI=0.253-0.940; p<0.05) compared to those without RT. No significant difference was observed in 5-year OS or DDFS. Subgroup analysis indicated a higher recurrence risk among patients with two to three positive lymph nodes or triple-negative tumors. Group B: Among patients who achieved ypN0 status, adjuvant RT significantly improved 5-year DFS (95.8% vs. 76.0%), OS (100.0% vs. 84.0%), and DDFS (100.0% vs. 80.0%) (p<0.05), with no significant difference in LRFS.

Conclusion: In stage II LVI-positive breast cancer patients, adjuvant RT improves local control and leads to an increase in DFS but not OS. PMRT provides survival benefits for LVI-positive patients who achieve ypN0 status after NAC and is recommended. Larger studies are needed to validate these findings.

Background/aim: A smooth transition to subsequent treatments is crucial for improving the prognosis of patients with metastatic colorectal cancer who receive chemotherapy. This study aimed to examine how patient factors at the initiation of treatment influence the feasibility of transitioning to subsequent treatments in patients who received trifluridine-tipiracil plus bevacizumab (FTD/TPI + Bev) therapy.

Patients and methods: This retrospective study included 80 patients treated with FTD/TPI + Bev therapy for metastatic colorectal cancer at Osaka City University Hospital between January 2016 and December 2023.

Results: Patients who were able to transition to subsequent treatments showed a significantly longer overall survival after the discontinuation of FTD/TPI + Bev therapy than those who were not. Immunonutritional indicators, such as the serum albumin concentration and Geriatric Nutritional Risk Index (GNRI), were significantly elevated in patients who were able to proceed to subsequent treatments in comparison to those who were not able to do so.

Conclusion: A poor immunonutritional status at the initiation of FTD/TPI + Bev therapy may lead to a lower rate of transitioning to subsequent treatments, thus resulting in a worse prognosis.

Background/aim: Adrenocortical carcinoma (ACC) is a rare adrenal cortex cancer (0.7-2.0 cases per million) with high malignancy and poor prognosis (5-year survival <40%). Early detection is difficult due to adrenal location, and effective treatments are lacking, highlighting the need for prognostic biomarkers and therapeutic targets. Anillin actin-binding protein (ANLN), a key regulator of cytokinesis, is overexpressed in many cancers compared with normal tissues and is associated with poor prognosis and advanced stage. However, the clinicopathological significance of ANLN in ACC remains unclear.

Materials and methods: ANLN mRNA expression and survival in patients with ACC [normal (n=128), stage I (n=9), stage II (n=37), stage III (n=16), stage IV (n=15)] were analyzed from TCGA database by using the UALCAN and GEPIA platforms, assessing ANLN mRNA expression across disease stages and its correlation with patient survival.

Results: ANLN was found to be significantly increased in stage IV ACC tissues compared with stage I, II and III ACC tissues (p<0.05). Furthermore, increased expression was significantly correlated with poor patient prognosis (p<0.005).

Conclusion: ANLN may be a prognostic biomarker for patients with ACC and may play a role in tumor biology. Further studies are needed to determine whether ANLN is clinically useful as a prognostic factor in the treatment of ACC and to clarify its involvement in the mechanism of malignant progression of ACC.

Background/aim: The Controlling Nutritional Status (CONUT) score, calculated using the serum albumin level, total cholesterol level (T-cho), and peripheral lymphocyte count, is a widely accepted prognostic marker for colorectal cancer (CRC). However, T-cho is often not measured in clinical practice, limiting its applicability. In the recently proposed modified CONUT (mCONUT) score, T-cho was replaced with hemoglobin concentration. This study evaluated the prognostic utility of the mCONUT score in patients with CRC undergoing curative resection.

Patients and methods: This study included 290 patients who underwent curative surgery for CRC at our institution between January 2017 and December 2019. The CONUT and mCONUT scores were calculated, and their prognostic values were assessed using the Cox proportional hazards regression analysis.

Results: Among 290 patients, 42 and 248 were assigned to the high and low CONUT groups, and 88 and 202 to the high and low mCONUT groups, respectively. Overall survival (OS) was significantly lower in the high CONUT and mCONUT groups (p<0.001). Multivariate analysis identified a high mCONUT score as an independent prognostic factor for poor OS (p=0.014).

Conclusion: Preoperative nutritional status affects CRC prognoses. Thus, the mCONUT score may be a useful prognostic marker.

Background/aim: Residual disease after neoadjuvant systemic therapy (NST) is strongly associated with prognosis in breast cancer. However, currently available indices such as the Residual Cancer Burden (RCB) and Neo-Bioscore are complex and not readily applicable in daily clinical practice. This study aimed to evaluate the prognostic significance of residual tumor morphology using only pathological T and N factors as a simple and clinically implementable index.

Patients and methods: Among 327 patients who received NST at our institution, 174 non-pathological complete response (non-pCR) cases who underwent axillary lymph node dissection were analyzed. Patients were classified according to the presence or absence of residual T and/or N factors (ypT+/ypN+, ypT+/ypN-, ypT-/ypN+). Disease-free survival (DFS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier and Cox regression analyses.

Results: Patients who achieved pCR had significantly better DFS and CSS (p<0.001 and p=0.010, log-rank) than those with residual disease. Among the non-pCR cohort, the ypT+/ypN+ group showed markedly worse DFS and CSS (p= 0.010 and p<0.001, log-rank) than patients without simultaneous residual T and N positivity. Multivariate analysis confirmed that concurrent ypT and ypN positivity was an independent predictor of poor DFS (hazard ratio=0.33; 95% confidence interval=0.17-0.62; p<0.001), along with high Ki67 expression.

Conclusion: Residual T and N positivity after NST represents a simple yet powerful prognostic indicator in breast cancer. This two-factor classification, easily derived from routine pathology, may serve as a practical reference for post-NST risk stratification and inform decisions regarding additional adjuvant treatment.

Background/aim: Pathologic stage II non-small cell lung cancer (NSCLC) exhibits heterogeneous outcomes despite curative resection. Although adjuvant EGFR-TKI and immunotherapy have improved survival in resected NSCLC, subgroup analyses from major trials show only modest benefit in stage II disease. Given these limited gains and the variable cost-effectiveness of adjuvant therapy across regions, identifying prognostic factors is essential to guide treatment decisions and support value-based precision care.

Patients and methods: We retrospectively analyzed 115 patients with pathologic stage II NSCLC (27 IIA, 88 IIB) who underwent complete resection at a tertiary hospital in Taiwan (2016-2023). Clinicopathologic variables-including histologic subtype, spread through air spaces (STAS), and lymphovascular invasion (LVI) - were reviewed. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox proportional hazards analyses.

Results: The 5-year RFS and OS rates were 50.9% and 67.9%, respectively. Independent predictors of recurrence included tumor size >4 cm [hazard ratio (HR)=2.88, p=0.008], N1 nodal status (HR=3.20, p=0.016), and high-risk adenocarcinoma subtype (micropapillary/solid; HR=2.80, p=0.014). Adjuvant chemotherapy significantly improved OS (76.4% vs. 37.2%, p=0.002).

Conclusion: Tumor size, nodal involvement, and histologic subtype are key prognostic determinants in stage II NSCLC. Identifying high-risk patients is crucial to optimize selection for adjuvant immunotherapy or targeted therapy and to ensure clinical and economic benefit.

Background/aim: Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide. This study aimed to clarify the oncogenic function of POM121 and its involvement in signaling pathways driving tumor progression.

Materials and methods: POM121 expression was analyzed in six GC cell lines and one normal gastric epithelial cell line, as well as in clinical datasets. Functional consequences of POM121 knockdown were assessed in AGS and KATO-III cells using cell proliferation, migration, soft agar colony formation, proteomic profiling, and in vivo xenograft models. Phosphorylation of p70S6 kinase at Thr389 and Thr421/Ser424 was examined to determine downstream signaling.

Results: POM121 was consistently found to be upregulated in GC tissues and cell lines. Silencing of POM121 significantly inhibited proliferation, migration, anchorage-independent growth, and tumorigenicity in vivo. Proteomic analysis revealed that suppression of POM121 attenuated phosphorylation of p70S6K at Thr389 and Thr421/Ser424, indicating impaired mTOR-p70S6K signaling.

Conclusion: POM121 promotes GC progression by enhancing proliferative and invasive phenotypes through p70S6 kinase-mediated signaling. These findings establish POM121 as a novel oncogene, prognostic biomarker, and potential therapeutic target in GC.

Background/aim: Colorectal cancer (CRC) remains a major global health challenge with poor survival in advanced disease. Identifying new oncogenic drivers is essential for improving diagnosis and therapy. This study investigated the oncogenic role of nucleophosmin 1 (NPM1) in CRC and its involvement in the AKT/mTOR signaling pathway.

Materials and methods: TCGA-COAD datasets were analyzed to compare NPM1 expression in tumor and normal tissues. Functional assays (MTT proliferation, soft agar colony formation, migration, and in vivo xenograft models) were performed after siRNA-mediated NPM1 knockdown in HCT-116 and DLD-1 cells. Western blotting and phospho-kinase arrays were used to evaluate phosphorylation of AKT, mTOR, and p70 S6 kinase.

Results: NPM1 expression was significantly upregulated in CRC tissues. Knockdown of NPM1 suppressed proliferation, migration, anchorage-independent growth, and in vivo tumorigenicity. Mechanistically, NPM1 depletion reduced phosphorylation of AKT, mTOR, and p70 S6 kinase, while total protein levels were unchanged. Downstream oncogenic regulators, including MYC and AP-1 components (c-Jun and c-FOS), were also decreased.

Conclusion: NPM1 acts as an oncogenic driver in colorectal cancer by activating the AKT/mTOR signaling pathway. Elevated NPM1 expression highlights its potential as a diagnostic, prognostic, and therapeutic biomarker in CRC.