Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumors

Viðarsdóttir, Halla; Siesing, Christina; Nodin, Björn; Jönsson, Per; Eberhard, Jakob; Jirström, Karin; Brunnström, Hans

doi:10.1002/jso.26375

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…In the present study, the expression of RBM3 was all over low, which can be conceived as being in line with that expected in mCRC. RBM3 was also found to be heterogeneously expressed and often higher in lymph node or peritoneal metastases than in primary tumours, which is in line with our previous study on colorectal lung metastases 55 . However, and notably, the highest expression was observed in one of the cases with poor prognosis.…”

Section: Discussionsupporting

confidence: 91%

“…Regarding RBM3 protein expression, previous studies have reported a largely consistent association between high expression and a favorable outcome, both in cohorts with mixed stages 53 , 54 , and in cohorts with mCRC only 18 , 55 . In the present study, the expression of RBM3 was all over low, which can be conceived as being in line with that expected in mCRC.…”

Section: Discussionmentioning

confidence: 75%

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Delineating the intra-patient heterogeneity of molecular alterations in treatment-naïve colorectal cancer with peritoneal carcinomatosis

et al. 2022

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In a non-negligible number of patients with metastatic colorectal cancer (mCRC), the peritoneum is the predominant site of dissemination. Cure can be achieved by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but this procedure is associated with long-term morbidity and high relapse rates. Thus, there is a pressing need for improved therapeutic strategies and complementary biomarkers. The present study explored the molecular heterogeneity in mCRC with peritoneal carcinomatosis (PC), and the potential clinical implications thereof. Multi-region immunohistochemical profiling and deep targeted DNA-sequencing was performed on chemotherapy-naïve tumours from seven patients with synchronous colorectal PC who underwent CRS and HIPEC. In total, 88 samples (5-19 per patient) were analysed, representing primary tumour, lymph node metastases, tumour deposits, PC and liver metastases. Expression of special AT-rich sequence-binding protein 2 (SATB2), a marker of colorectal lineage, was lacking in the majority of cases, and a conspicuous intra-patient heterogeneity was denoted for expression of the proposed prognostic and predictive biomarker RNA-binding motif protein 3 (RBM3). Loss of mismatch repair proteins MLH1 and PSM2, observed in one case, was concordant with microsatellite instability and the highest tumour mutational burden. When present in a patient, mutations in key CRC driver genes, i.e., KRAS, APC and TP53, were homogenously distributed across all samples, while less common mutations were more heterogenous. On the same note, copy number variations showed intra-patient as well inter-patient heterogeneity. In two out of seven cases, hierarchical clustering revealed that samples from the PC and lymph node metastases were more similar to each other than to the primary tumour. In summary, these findings should encourage additional studies addressing the potential distinctiveness of mCRC with PC, which might pave the way for improved personalized treatment of these patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 75%

Delineating the intra-patient heterogeneity of molecular alterations in treatment-naïve colorectal cancer with peritoneal carcinomatosis

et al. 2022

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“…Survival in patients after pulmonary metastasectomy for colorectal lung metastases with tumors harboring RAS, BRAF and TP53 mutations were found to be worse than patients with wild type of RAS, BRAF and TP53 gene (48)(49)(50). On the other hand, APC gene and low expression of RNA-binding motif protein 3 expression were associated with better survival after pulmonary metastasectomy (51). Tumor biology appears to play a significant role in the survival of CRC patients with metastatic disease.…”

Section: Indication and Patient Selection Of Pulmonary Metastasectomymentioning

confidence: 89%

Lung metastases from colorectal cancer: a multidisciplinary approach and role of local treatment: a narrative review

Hsin¹

2022

AME Surg J

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Colorectal cancer is a common malignancy causing morbidity and mortality. Despite advances in screening and early surgical treatment of colorectal primary tumor, metastases to different organs, including the liver and lung, is still prevalent. Treatment options for colorectal lung metastases, including systemic chemotherapy, targeted therapy, radiotherapy, surgical resection of lung metastases, tumor ablation, have been studied widely in the hope of improving patient survival. This review article will focus on local treatment of colorectal lung metastases. We present the following article in accordance with the narrative review reporting checklist (available at

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Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial: a systematic review of published responses

Williams

Patrick

Fiorentino

et al. 2022

European Journal of Cardio-Thoracic Surgery

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and keywords Objectives The objective of this review was to assess the nature and tone of the published responses to the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial. Methods Published articles that cited the PulMiCC trial were identified from Clarivate Web of Science (©. Duplicates and self-citations were excluded and relevant text extracted. Four independent researchers rated the extracts independently using agreed scales for the representativeness of trial data and the textual tone. The ratings were aggregated and summarized. Two PulMiCC authors carried out a thematic analysis of the extracts. Results Sixty-four citations were identified and relevant text was extracted and examined. The consensus rating for data inclusion was a median of 0.25 out of 6 (range 0 to 5.25, IQR 0–1.5) and for textual tone the median rating was 1.87 out of 6 (range 0 to 5.75, IQR 1–3.5). The majority of citations did not provide adequate representation of the PulMiCC data and the overall the textual tone was dismissive. Although some were supportive, many discounted the findings because the trial closed early and was underpowered to show non-inferiority. Two misinterpreted the authors’ conclusions but there was acceptance that five-year survival was much higher than widely assumed. Conclusions Published comments reveal a widespread reluctance to consider seriously the results of a carefully conducted randomized trial. This may be because the results challenge accepted practice because of ‘motivated reasoning’. But there is a widespread misunderstanding of the fact that though PulMiCC with 93 patients was underpowered to test non-inferiority, it still provides reliable evidence to undermine the widespread belief in a major survival benefit from metastasectomy.

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Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumors

Cited by 5 publications

References 54 publications

Delineating the intra-patient heterogeneity of molecular alterations in treatment-naïve colorectal cancer with peritoneal carcinomatosis

Delineating the intra-patient heterogeneity of molecular alterations in treatment-naïve colorectal cancer with peritoneal carcinomatosis

Lung metastases from colorectal cancer: a multidisciplinary approach and role of local treatment: a narrative review

Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial: a systematic review of published responses

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