Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn.However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/ SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/ SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/ SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/ SSR4 is a potential oncogene in human colorectal cancer cells.

Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn.However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/ SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/ SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/ SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/ SSR4 is a potential oncogene in human colorectal cancer cells.

Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn.However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/ SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/ SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/ SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/ SSR4 is a potential oncogene in human colorectal cancer cells.

Purpose: Bone age (BA) is needed to assess developmental status and growth disorders. We evaluated the clinical performance of a deep-learning-based BA software to estimate the chronological age (CA) of healthy Korean children. Methods: This retrospective study included 371 healthy children (217 boys, 154 girls), aged between 4 and 17 years, who visited the Department of Pediatrics for health check-ups between January 2017 and December 2018. A total of 553 left-hand radiographs from 371 healthy Korean children were evaluated using a commercial deep-learning-based BA software (BoneAge, Vuno, Seoul, Korea). The clinical performance of the deep learning (DL) software was determined using the concordance rate and Bland-Altman analysis via comparison with the CA. Results: A 2-sample t-test (P<0.001) and Fisher exact test (P=0.011) showed a significant difference between the normal CA and the BA estimated by the DL software. There was good correlation between the 2 variables (r=0.96, P<0.001); however, the root mean square error was 15.4 months. With a 12-month cutoff, the concordance rate was 58.8%. The Bland-Altman plot showed that the DL software tended to underestimate the BA compared with the CA, especially in children under the age of 8.3 years. Conclusion The DL-based BA software showed a low concordance rate and a tendency to underestimate the BA in healthy Korean children.

Purpose: This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. Materials and Methods: We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. Results: The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). Conclusion In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

Purpose: We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors. Results: The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026). Conclusion PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

Purpose: We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non–small cell lung cancer (LA-NSCLC). Materials and Methods: Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS). Results: PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001). Conclusion PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.

Purpose: Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Materials and Methods: Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction. Results: We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. Conclusion The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Purpose: This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus–positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment. Materials and Methods: This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT. Results: With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding. Conclusion We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

Purpose: The purpose of this study was to evaluate the treatment outcomes and toxicity profile of patients with early glottic cancer who underwent hypofractionated radiation therapy (RT) with 3.5 Gy per fraction. Materials and Methods: A retrospective review was performed of the medical records of 35 patients with early stage (T1-2N0M0) glottic cancer who underwent definitive RT. The dose fractionation scheme was 59.5 Gy in 17 fractions. Posterior commissure was excluded from the clinical target volume (CTV) for 26 patients (74.3%) without glottic lesions close to this region. Results: With a median follow-up of 16.23 months (range, 6.82 to 67.15 months), no local, regional, or distant recurrence was reported. Acute hoarseness (65.7%), mucositis (68.6%), radiation dermatitis (60.0%) was frequent. One patient (2.9%) reported grade 3 acute toxicity (mucositis) and there was no grade 4–5 acute toxicity. There was no grade ≥3 late toxicities; however, grade 1 late intermittent hoarseness was frequent (45.7%). The receiver operative characteristic analysis revealed that mean hypopharyngeal dose was predictive for acute grade ≥2 mucositis (area under the curve=0.9314; 95% confidence interval, 0.8524–1). The optimal threshold of mean hypopharyngeal dose for occurrence of acute grade ≥2 mucositis was 26.31 Gy, with a specificity and sensitivity of 83.3% and 88.2%, respectively. Conclusion Hypofractionated RT with fraction size of 3.5 Gy for early glottic cancer is effective. The hypopharyngeal mean dose could predict the occurrence of grade ≥2 acute mucositis. The posterior commissure can be safely excluded from the CTV.