International Journal of Cancer最新文献

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p = .03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p = .01, HR 0.27; p < .01, HR 0.19; p < .01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p = .51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy.

Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.

To evaluate different Lynch syndrome (LS) screening approaches and establish an efficient and sensitive strategy are critical for clinical practice. In total, 583 patients with colorectal carcinoma (CRC) at Fudan University Shanghai Cancer Center were enrolled. Patient samples were examined by immunohistochemistry (IHC) and next-generation sequencing (NGS), and MLH1 promoter hypermethylation (MPH) was detected in MLH1-deficient cases. Germline genetic testing was performed in cases with deleterious variants and large genomic rearrangements (LGRs) of tumor MMR genes were detected in cases with dMMR or MSI-H cases with no MMR germline variants. Our results showed that triage with IHC and followed by BRAF/MLH1 methylation testing (Strategy 1) identified 93.3% (70/75) of LS cases. IHC followed by germline NGS (Strategy 2) or direct tumor NGS (Strategy 3) both identified 98.7% (74/75) of LS cases. The proportion of LGRs in LS cases was 16.0% (12/75), while 84.0% (63/75) showed SNV/Indel. The average cost per patient was ¥6010.81, ¥6058.48, and ¥8029.98 for Strategy 1, Strategy 2 and Strategy 3, respectively. The average time spent on different strategies was 4.74 days (Strategy 1), 4.89 days (Strategy 2), and 14.50 days (Strategy 3) per patient, respectively. LS and Lynch-like syndrome (LLS) were associated with an earlier onset age than MPH. In conclusion, we compared different workflows for LS screening and IHC plus germline NGS is recommended for LS screening when taking sensitivity, time, and cost into account. Moreover, multiplex ligation-dependent probe amplification made up for the shortcoming of NGS and should be incorporated into routine screening.

No study has unequivocally proven that chemotherapy prolongs overall survival (OS) in advanced esophageal cancer. We conducted a Phase III randomized study in first-line advanced unresectable/metastatic esophageal/GEJ cancer. Patients aged 18-70 years, with performance status 0-2, were randomized to best supportive care (BSC) alone, or BSC with weekly paclitaxel 80 mg/m². BSC comprised, as indicated, education, counselling, radiation, stenting, feeding tube placement, nutritional supplementation, medications like analgesics, and referral to a support group and palliative care. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), response, toxicity, and QoL. Between May 2016-December 2020, we recruited 281 patients: 143 to chemotherapy and 138 to BSC. Histopathology was squamous in 269 (95.7%) patients. Median number of paclitaxel doses was 12 (IQR, 7-23). Median OS was 4.2 months (95% CI, 3.42-5.32) in BSC, and 9.2 months (95% CI, 8.02-10.48) in chemotherapy; HR, 0.49 (95% CI, 0.39-0.64); p < .001. As compared to BSC, chemotherapy increased response (2.9% to 39%), median PFS (2.1 to 4.2 months), 1-year OS (11% to 32%), 2-year OS (0 to 9%), median dysphagia-free survival (2.9 to 14.8 months), and global and esophagus-specific QoL, without significantly increasing all-grade or grade ≥3 toxicities. Using ESMO clinical benefit scale and ASCO Value Framework, palliative chemotherapy scored as having "substantial value." Our study provides the first level 1 evidence that chemotherapy prolongs survival in advanced esophageal/GEJ carcinoma. BSC alone is no longer appropriate. Weekly paclitaxel is an attractive option, especially in LMICs with limited access to immunotherapy.

Expression of Concern: X. Zhu, Y. Li, C. Xie, X. Yin, Y. Liu, Y. Cao, Y. Fang, X. Lin, Y. Xu, W. Xu, H. Shen, J. Wen, “ miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6,” International Journal of Cancer 135, no. 6 (2014): 1286–1296. https://doi.org/10.1002/ijc.28774.

This Expression of Concern is for the above article, published online on 08 February 2014, in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Prof. Christoph Plass; the Union for International Cancer Control; and John Wiley and Sons Ltd. The Expression of Concern has been agreed due to concerns raised by a third party regarding the similarity of blots between Figures 3j and 4a. The β-actin bands in Figure 3j for the cell line SKOV3/PTX appear similar to that in Figure 4a for the cell line A2780/PTX. The authors responded to an inquiry by the publisher, but were not able to supply original data or images. The journal is issuing this Expression of Concern because the results of the experiment as presented cannot be confirmed.

Optimizations are expected in the development of immunotherapy for the treatment of Triple-negative breast cancer (TNBC). We studied the expression of galectin-9 (Gal-9) after irradiation and assessed the differential impacts of its targeting with or without radiotherapy. Tumor resections from TNBC patients who received neoadjuvant radiotherapy revealed higher levels of Gal-9 in comparison to their baseline level, only in non-responder patients. Gal-9 expression was also found to be increased in TNBC tumor biopsies and cell lines after irradiation. We investigated the therapeutic advantage of targeting Gal-9 after radiotherapy in mice. Irradiated 4T1 cells or control non-irradiated 4T1 cells were injected into BALB/c mice. Anti-Gal-9 antibody treatment decreased tumor progression only in mice injected with irradiated 4T1 cells. This proof-of-concept study demonstrates that Gal-9 could be considered as a dynamic biomarker after radiotherapy for TNBC and suggests that Gal-9 induced-overexpression could represent an opportunity to develop new therapeutic strategies for TNBC patients.

C. Wagener, R. C. Bargou, P. T. Daniel, K. Bommert, M. Y. Mapara, H. D. Royer, and B. Dörken, “ Induction of the Death-Promoting Gene bax-α Sensitizes Cultured Breast-Cancer Cells to Drug-Induced Apoptosis,” International Journal of Cancer 67, no. 1 (1996): 138–141, https://doi.org/10.1002/(SICI)1097-0215(19960703)67:1<138::AID-IJC22>3.0.CO;2-9.

This Expression of Concern is for the above article, first published on 3 July 1996 and available in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, Prof. Christoph Plass; the Union for International Cancer Control; and John Wiley & Sons Ltd. The Expression of Concern was agreed due to concerns about the Western Blot bands in Figure 1 and Figure 2.

The Western Blot shown in Figure 2 was also included as Figure 3 in another publication by this author group [1]. However, this other publication was not cited.

In Figure 1, the Western Blot bands for Bcl-2 and Bcl-xL look very similar to the tubulin bands in the right panel of Figure 3 in Bargou et al. [1] (tubulin for “bax” in MCF-7 and for “bax” in R30C, respectively). The authors are unable to retrieve the original data underlying this experiment due to the time that has elapsed and state that they cannot rule out inadvertent mislabelling of the figure.

As these issues cannot be definitively resolved, the journal is publishing this Expression of Concern to alert readers. The authors R. C. Bargou and K. Bommert agree to this Expression of Concern. C. Wagener, P. T. Daniel, M. Y. Markus, H. D. Royer, and B. Dörken were not reachable.

Head and neck squamous cell carcinomas (HNSCCs) are linked to tobacco smoking, opium use, and human papillomavirus (HPV) infection. However, little is known about the association of HPV infection with risk factors of HNSCCs, including opium and tobacco use. This cross-sectional analysis of a national multi-center case–control study in Iran included 498 HNSCC cases and 242 controls. We investigated the association of opium and tobacco use with α- (n = 21), β- (n = 46), and γ-HPV (n = 52) types in saliva samples using type-specific bead-based multiplex genotyping assays (TS-MPG). We found that α-HPV positivity was significantly associated with tobacco smoking (OR = 10.35; 95% CI = 1.15, 93; p = .03), but not with opium use (OR = 1.06; 95% CI = 0.41, 2.76; p = .89). Additionally, tobacco smoking correlated with an elevated risk of β-species 2 HPV infection (OR = 1.28; 95% CI = 1.04, 1.58; p = .020). Conversely, opium use showed a positive association with γ-species 12 HPV infection (OR = 5.67; 95% CI = 1.43, 22.44; p = .013). These findings indicate that tobacco and opium use may influence the risk of HPV infection in different ways depending on the HPV genus and species. Further studies are needed to replicate these findings in other populations.

Chen, Y., Zhao, F., Cui, D., Jiang, R., Chen, J., Huang, Q. and Shi, J. (2018), HOXD-AS1/miR-130a sponge regulates glioma development by targeting E2F8. Int. J. Cancer, 142: 2313–2322. https://doi.org/10.1002/ijc.31262.

This Expression of Concern is for the above article, published online on 17 January 2018 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Christoph Plass, the Union for International Cancer Control and John Wiley & Sons, Ltd.

The Expression of Concern has been agreed due to concerns raised by third parties regarding the data presented in Figure 5b and 5c. Specifically, the si-NC panel in Figure 5b (cell migration) appears to overlap with the si-NC panel in Figure 5c (cell invasion) when rotated. The authors acknowledged that the image for si-NC in Figure 5c was mislabeled and that they were no longer able to locate the original image underlying si-NC in Figure 5c due to problems with data storage. Additionally, it has come to the attention of the journal that in Figure 4c the blots displaying the loading control β-actin do not originate from the same blots where E2F7 and E2F8 were detected. The authors have indicated that E2F7, E2F8, and β-actin expression levels were detected on different membranes. However, they assure that the same experimental protocol was rigorously followed. The journal has issued this Expression of Concern to inform and alert readers.