International Journal of Cancer. Journal International du Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts...

Tumor-informed mutation-based approaches are frequently used for detection of circulating tumor DNA (ctDNA). Not all mutations make equally effective ctDNA markers. The objective was to explore if prioritizing mutations using mutational features-such as cancer cell fraction (CCF), multiplicity, and error rate-would improve the success rate of tumor-informed ctDNA analysis. Additionally, we aimed to develop a practical and easily implementable analysis pipeline for identifying and prioritizing candidate mutations from whole-exome sequencing (WES) data...

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity...

Metastatic melanoma is still a difficult-to-treat cancer type owing to its frequent resistance mechanisms to targeted and immunotherapy. Therefore, we aimed to unravel novel therapeutic strategies for melanoma patients. Preclinical and clinical studies show that melanoma patients may benefit from a treatment with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). In this study, we focus on PARP1 as a potential biomarker to predict the response of melanoma cells to PARPi therapy. We found that melanoma cells with high basal PARP1 expression exhibit significantly increased cell death after PARPi treatment owing to higher PARP1 trapping compared with melanoma cells with low PARP1 expression...

Chimeric RNAs, which can arise from gene recombination at the DNA level or non-canonical splicing events at the RNA level, have been identified as important roles in human tumors. Dysregulated gene expression caused by somatic mutations and altered splicing patterns of oncogenes or tumor suppressor genes can contribute to the development of tumors. Therefore, investigating the formation mechanism of chimeric RNAs via somatic mutations is critical for understanding tumor pathogenesis. This project is the first to propose studying the association between somatic single nucleotide variants and chimeric RNAs, identifying around 2900 somatic SNVs affecting chimeric RNAs in pan-cancer level...

Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression-free survival (PFS), overall survival (OS), survival-independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first-line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs)...

Although the survival rate of patients with childhood cancer has greatly improved, long-term survivors face specific problems such as the late effects of cancer treatment. In this study, we estimated the number of people who had experienced childhood cancer to predict their needs for medical care and social resources. Using data from the population-based Osaka Cancer Registry, we identified children aged 0-14 years who were diagnosed with cancer between 1975 and 2019. We estimated the prevalence on December 31, 2019, and the 5- and 10-year prevalence (i...

Early detection is critical for improving pancreatic cancer prognosis. Our study aims to identify circulating microRNAs (miRNAs) associated with pancreatic cancer risk. The two-stage study used plasma samples collected ≤5 years prior to cancer diagnosis, from case-control studies nested in five prospective cohort studies. The discovery stage included 185 case-control pairs from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Replication stage samples comprised 277 pairs from Shanghai Women's Health Study/Shanghai Men's Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study...

Treatment resistance remains a major issue in aggressive prostate cancer (PC), and novel genomic biomarkers may guide better treatment selection. Circulating tumor DNA (ctDNA) can provide minimally invasive information about tumor genomes, but the genomic landscape of aggressive PC based on whole-genome sequencing (WGS) of ctDNA remains incompletely characterized. Thus, we here performed WGS of tumor tissue (n = 31) or plasma ctDNA (n = 10) from a total of 41 aggressive PC patients, including 11 hormone-naïve, 15 hormone-sensitive, and 15 castration-resistant patients...

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study)...

Nasopharyngeal carcinoma (NPC) has a unique geographic distribution. It is unknown whether meteorological factors are related to the incidence of NPC. To investigate the effect of ambient temperature, relative humidity (RH), and absolute humidity (AH) on the incidence of NPC, we collected the incidence rate of NPC in 2016 and meteorological data from 2006 to 2016 from 484 cities and counties across 31 provinces in China. Generalized additive models with quasi-Poisson regression and generalized linear models with natural cubic splines were employed respectively to elucidate the nonlinear relationships and specify the partial linear relationships...

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram...

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method...

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC)...

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016...

In sub-Saharan Africa, colorectal cancer (CRC) has historically been considered a rare disease, although some previous studies have suggested that the incidence is increasing. We examine time trends in the incidence of CRC using data from 12 population-based cancer registries in 11 countries of sub-Saharan Africa that were able to provide time series data for periods of 12 or more years, or with earlier data with which recent rates may be compared. Age-standardized incidence rates were highest in the higher-income countries, and were increasing in all of the populations studied, and these increases were statistically significant in all but three...

Whether trace metals modify breast density, the strongest predictor for breast cancer, during critical developmental stages such as puberty remains understudied. Our study prospectively evaluated the association between trace metals at Tanner breast stage B1 (n = 291) and at stages both B1 and B4 (n = 253) and breast density at 2 years post-menarche among Chilean girls from the Growth and Obesity Cohort Study. Dual-energy x-ray absorptiometry assessed the volume of dense breast tissue (absolute fibroglandular volume [FGV]) and percent breast density (%FGV)...

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19...

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Patients treated for oral cancer, may experience restricted mouth opening (trismus). Barriers such as cost have limited the utilization of traditional jaw stretching devices, and consequently, patients experience problems with swallowing, oral care, communication, and cancer surveillance. The safety and efficacy of Restorabite™, a new device designed to overcome these barriers, is evaluated prospectively over 12 months. This phase II investigator-led trial included patients with chronic trismus underwent 10-weeks of trismus therapy using Restorabite™...