Cancer Research and Treatment最新文献

Purpose: We aimed to develop a preoperative risk scoring system to predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICCA) after resection, utilizing clinical and computed tomography (CT) features.

Materials and methods: This multicenter study included 365 patients who underwent curative-intent surgical resection for ICCA at six institutions between 2009 and 2016. Of these, 264 patients from one institution constituted the development cohort, while 101 patients from the other institutions constituted the external validation cohort. Logistic regression models were constructed to predict ER based on preoperative variables and were subsequently translated into a risk scoring system. The discrimination performance of the risk scoring system was validated using external data and compared to the American Joint Committee on Cancer (AJCC) TNM staging system.

Results: Among the 365 patients (mean age, 62±10 years), 153 had ER. A preoperative risk scoring system that incorporated both clinical and CT features demonstrated superior discriminatory performance compared to the postoperative AJCC TNM staging system in both the development (area under the curve [AUC], 0.78 vs. 0.68; p=0.002) and validation cohorts (AUC, 0.69 vs. 0.66; p=0.641). The preoperative risk scoring system effectively stratified patients based on their risk for ER: the 1-year recurrence-free survival rates for the low, intermediate, and high-risk groups were 85.5%, 56.6%, and 15.6%, respectively (p < 0.001) in the development cohort, and 87.5%, 58.5%, and 25.0%, respectively (p < 0.001) in the validation cohort.

Conclusion: A preoperative risk scoring system that incorporates clinical and CT imaging features was valuable in identifying high-risk patients with ICCA for ER following resection.

Purpose: This study examined the roles of nuclear factor erythroid 2-related factor 2 (NRF2) and programmed death ligand 1 (PD-L1) in colon carcinogenesis, underscoring on sex and differences in tumor location.

Materials and methods: A total of 378 participants were enrolled from Seoul National University Bundang Hospital: 88 healthy controls (HC), 139 patients with colorectal adenoma (AD), and 151 patients with colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (PCR), methylation-specific PCR, and immunohistochemistry (IHC) were performed utilizing tumor samples from patients and normal mucosa in the HC group.

Results: NRF2 mRNA expression was higher in the CRC group than in the HC and AD groups, with decreased NRF2 methylation in the AD and CRC groups. NRF2 protein expression, as evaluated by IHC, increased in the AD and CRC groups relative to that in the HC group. PD-L1 protein expression was remarkably higher in the CRC group than in the HC and AD groups. These patterns were consistent in both males and females. In sex- and CRC location-specific analyses, NRF2 methylation was lower in female than in male patients with CRC. NRF2 protein expression was significantly higher in females, particularly in patients with right-sided CRC. Moreover, females exhibited increased PD-L1 mRNA expression compared to males in the AD group, and PD-L1 mRNA levels were higher in females with right-sided CRC than in those with cancer at other locations.

Conclusion: Differences in NRF2 and PD-L1 expression indicate site-specific colon carcinogenesis based on sex, particularly in females with right-sided CRC.

Purpose: Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.

Materials and methods: One thousand one hundred thirty LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA sequencing (RNA-seq), experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.

Results: A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% confidence interval, 0.729 to 0.804). Additionally, we identified acyl-CoA synthetase long-chain family member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (p < 0.001) and overall survival (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon-α secretion, as indicated by bulk RNA-seq and enzyme-linked immunosorbent assay analysis, thereby promoting the infiltration of antitumor immune cells.

Conclusion: The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

Purpose: As understanding of the molecular pathogenesis of endometrial carcinoma (EC) advanced, the International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2023. This study compared EC survival outcomes using the 2009 and 2023 FIGO staging systems.

Materials and methods: We retrospectively analyzed 3,029 patients diagnosed with 2009 FIGO stage I-III EC between 1985 and 2022 in South Korea, and between 2020 and 2022 in Taiwan. All patients were reclassified using the 2023 FIGO staging, and survival and risk factors were examined under both systems.

Results: Transitioning from the 2009 to 2023 FIGO resulted in 549 patients (18.0%) being upstaged and their survival curves being diversified, indicating significant prognostic value of the 2023 FIGO. Re-classification using the 2023 FIGO upstaged the 2009 FIGO stage IA high-risk ECs, allowing more intensive treatment and potentially improving survival outcomes. The most significant changes occurred in the 2009 FIGO stages IA, IB, and IIIA ECs: upstaging in 16.5%, 49.0%, and 2.0% of IA, IB, and IIIA tumors, respectively, and downstaging 0.3% and 40.8% of IB and IIIA tumors, respectively. The risk factors for poor survival included old age (≥ 60 years), menopause, diabetes, substantial lymphovascular space invasion, aberrant p53 expression, and some aggressive histological types (carcinosarcoma, undifferentiated carcinoma, mesonephric-like adenocarcinoma, and neuroendocrine carcinoma).

Conclusion: The 2023 FIGO staging provides more refined stratification of early-stage EC than the 2009 version. Thus, the 2023 FIGO may more accurately guide prognosis and therapeutic decision-making.

Purpose: This study focused on combining irinotecan with poly(ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).

Materials and methods: We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for 7 days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.

Results: We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DDR pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC50 fold changes for PARP inhibitors were as follows: olaparib, 1,649±4,049; talazoparib, 25±34.21; venadaparib, 336±596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.

Conclusion: This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

Purpose: This study aimed to evaluate the clinical impact of main tumor resection on long-term survival compared with pleural biopsy alone in patients with lung adenocarcinoma who were intraoperatively diagnosed with pleural metastasis.

Materials and methods: A total of 176 patients with adenocarcinoma who had unexpected pleural metastasis detected during surgery from 2002 to 2021 were retrospectively analyzed. Each surgeon decided whether to perform main tumor resection or pleural biopsy alone.

Results: The patients were grouped based on the surgical approaches: main tumor resection (resection group; n=83) and pleural biopsy only (O&C group; n=93). The resection group had better overall survival (OS; 10-year survival, 27.9% vs. 9.4%; median survival, 68.3 vs. 36.6 months; p < 0.01) and locoregional progression-free survival (10-year survival, 12.5% vs. 7.1%; median survival, 19.6 vs. 10.6 months; p < 0.01) than the O&C group. Similar results were found for OS in patients who received tyrosine kinase inhibitors (TKIs) as first-line therapy (10-year survival, 49.2% vs. 15.0%; median survival, 72.2 vs. 45.4 months; p=0.03), patients who did not undergo TKIs treatment (10-year survival, 29.4% vs. 9.2%; median survival, 82.4 vs. 23.8 months; p < 0.01), and patients with positive target gene mutation (10-year survival, 31.7% vs. 10.1%; median survival, 72.2 vs. 33.7 months; p < 0.01). In multivariate analysis, pleural biopsy only (hazard ratio, 1.73; p=0.04) was a significant predictor of OS.

Conclusion: Main tumor resection can improve survival in patients with lung adenocarcinoma who had unexpected pleural metastasis during operation.

Purpose: Previous studies suggested an association between alcohol consumption and reduced kidney cancer risk. Given a potential interaction between alcohol's insulin-sensitizing effect and hyperglycemia-related insulin resistance, we aimed to assess whether the dose-response association between alcohol intake and kidney cancer risk varies based on glycemic status.

Materials and methods: This nationwide cohort study analyzed data from 9,492,331 adults who underwent a national health screening program in 2009 and were followed until 2018. Multivariable-adjusted Cox regression models were applied to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Over a median follow-up period of 8.3 years, 12,381 participants were diagnosed with kidney cancer. A U-shaped relationship between alcohol consumption and kidney cancer risk was observed among individuals with normoglycemia (light-to-moderate: HR, 0.94; 95% CI, 0.89 to 0.99 and heavy: HR, 1.00; 95% CI, 0.91 to 1.09, respectively). In prediabetic individuals, alcohol consumption was not significantly associated with kidney cancer risk. In individuals with diabetes, a dose-dependent increase in kidney cancer risk was noted with higher alcohol consumption (light-to-moderate consumption: HR, 1.12; 95% CI, 1.03 to 1.22; heavy consumption: HR, 1.24; 95% CI, 1.09 to 1.42; p for trend < 0.01).

Conclusion: A modest U-shaped dose-response association between alcohol consumption and kidney cancer risk was observed exclusively in individuals with normoglycemia. Individuals with diabetes demonstrated a dose-dependent increased risk of kidney cancer with higher alcohol consumption. Tailored patient education and personalized risk assessments regarding alcohol consumption and kidney cancer risk should be emphasized over a generalized 'one-size-fits-all' approach.

Purpose: Smoking cessation interventions for participants in lung cancer screening are essential for increasing the effectiveness of screening to reduce lung cancer mortality. This study aimed to investigate the factors that lead to smoking cessation after lung cancer screening.

Materials and methods: The Korean National Lung Cancer Screening (KNLCS) Satisfaction Survey was conducted from 2021 to 2022 with approximately 1,000 samples per year among participants in KNLCS targeting 30 or more pack-year smokers. Factors associated with smoking cessation were analyzed based on the survey.

Results: Among 1,525 current smokers in the survey participants, 728 (47.7%) received screening result counseling from physician after screening and showed significantly higher smoking cessation rate than non-counseling participants (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.27 to 3.70). The participants who considered the counseling helpful were more likely to quit smoking (OR, 3.53; 95% CI, 2.00 to 6.22) and to reduce smoking amount (OR, 2.05; 95% CI, 1.54 to 2.71). Similarly, those who received physicians' active recommendations to quit smoking were likely to quit smoking (OR, 2.20; 95% CI, 1.25 to 3.87) and to decrease smoking amount (OR, 1.30; 95% CI, 1.00 to 1.68). In contrast, participants who had no abnormal findings from screening tended to have no significant change in smoking status despite the physicians' active recommendations to quit smoking.

Conclusion: Physicians' active recommendations and effective counseling to quit smoking could be a key factor in increasing smoking cessation among lung cancer screening participants. Further research should be conducted to develop more effective strategies for smoking cessation to participants without abnormal findings in lung cancer screening.

Purpose: This study aimed to compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on epidermal growth factor receptor (EGFR) amplification status.

Materials and methods: Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least five copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥ 6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp-).

Results: Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp- patients (median OS [mOS], 76 vs. 37 months; p=0.145). Among 572 patients who received anti-EGFR antibody-based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp- patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp- patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344).

Conclusion: This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

Purpose: Widely used breast cancer risk-prediction tools are based on data from Western countries, but risk factors may differ for Asian women. Hence, we aimed to develop a risk assessment tool for breast cancer in Asian women using a nationwide, population-based mammographic screening cohort.

Materials and methods: Women aged ≥ 40 years who underwent breast cancer screening and general health examination in 2009 were included. Age, body mass index (BMI), breast density, lifestyle and reproductive factors, and comorbidities were used to develop 5-year breast cancer risk-prediction models for premenopausal (n=771,856) and postmenopausal (n=1,108,047) women at baseline. The best-fit risk prediction model was constructed using backward stepwise selection in a Cox proportional hazards model and was transformed into a risk score nomogram. The performance was assessed by discrimination and calibration.

Results: In premenopausal women, high BMI, low parity, short breastfeeding period, early age at menarche, high breast density, a history of benign breast masses, and family history of breast cancer contributed to the risk prediction of breast cancer. In postmenopausal women, age, diabetes mellitus, dyslipidemia, late-onset menopause, and hormone replacement therapy use were additional risk predictors of breast cancer. Our risk-prediction model showed a concordant statistic of 0.58 (0.57-0.59) for premenopausal women and 0.64 (0.63-0.65) for postmenopausal women. The calibration plot demonstrated good correlations for both models.

Conclusion: Our breast cancer risk-prediction model demonstrated performance comparable to that of Western countries, especially among postmenopausal women. This provides a foundation for implementing risk-based screening recommendations in Asian women.