Genome-Wide Scan for Copy Number Alteration Association with Relapse-Free Survival in Colorectal Cancer with Liver Metastasis Patients

Predicting a patient’s risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes—S100PBP, CSMD2, TGFBI—significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy.

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Histologically Verified Biliary Invasion was Associated with Impaired Liver Recurrence-Free Survival in Resected Colorectal Cancer Liver Metastases

Scandinavian Journal of Surgery ◽

10.1177/1457496918812237 ◽

2018 ◽

Vol 108 (3) ◽

pp. 201-209 ◽

Cited By ~ 2

Author(s):

P. Reijonen ◽

P. Österlund ◽

H. Isoniemi ◽

J. Arola ◽

A. Nordin

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Liver Metastasis ◽

Liver Metastases ◽

Recurrence Free Survival ◽

Colorectal Cancer Liver Metastases ◽

Free Survival ◽

Colorectal Cancer Liver Metastasis ◽

Liver Recurrence ◽

Disease Free

Background and Aims: The impact of biliary invasion on recurrence and survival, after resection of colorectal cancer liver metastases, is not well known as publications are limited to small patient series. The aim was to investigate if biliary invasion in liver resected patients associated with liver relapses and recurrence-free survival. Secondary endpoints included association with other prognostic factors, disease-free survival and overall survival. Materials and Methods: All patients with histologically verified biliary invasion (n = 31, 9%) were identified among 344 patients with liver resection between January 2009 and March 2015. Controls (n = 78) were selected from the same time period and matched for, among others, size and number of colorectal cancer liver metastasis. Results: Median liver recurrence-free survival was significantly shorter in patients with biliary invasion than in controls (15.3 months versus not reached; p = 0.031) and more relapses were noted in the liver (61.3% versus 33.3%; p = 0.010), respectively. In univariate analyses for liver recurrence-free survival, biliary invasion was the only significant prognostic factor; p = 0.034. There were no statistical differences in disease-free and overall survival between the groups. Conclusion: Biliary invasion was associated with higher liver recurrence rates and shorter liver recurrence-free survival in patients with resected colorectal cancer liver metastasis.

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SURGICAL OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH SYNCHRONOUS COLORECTAL LIVER METASTASES

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032014000100002 ◽

2014 ◽

Vol 51 (1) ◽

pp. 4-9 ◽

Cited By ~ 1

Author(s):

Rafael FONTANA ◽

Paulo HERMAN ◽

Vincenzo PUGLIESE ◽

Marcos Vinicius PERINI ◽

Fabricio Ferreira COELHO ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Liver Metastasis ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Disease Free Survival ◽

Term Survival ◽

Free Survival ◽

Disease Free

Context Colorectal cancer is the second most prevalent cancer worldwide, and the liver is the most common site of metastases. Surgical resection of colorectal liver metastases provides the sole possibility of cure and the best odds of long-term survival. Objectives To describe surgical outcomes and identify features associated with disease prognosis in patients submitted to synchronous colorectal cancer liver metastasis resection. Methods Retrospective study of 59 patients who underwent surgery for synchronous colorectal cancer liver metastasis. Actuarial survival and disease-free survival were assessed, depending on the prognostic variable of interest. Results Postoperative mortality and morbidity rates were 3.38% and 30.50% respectively. Five-year disease-free survival was estimated at 23.96%, and 5-year overall survival, at 38.45%. Carcinoembryonic antigen levels ≥50 ng/mL and presence of three or more liver metastasis were limiting factors for disease-free survival, but did not affect late survival. No patient with liver metastases and extrahepatic disease had disease-free interval longer than 20 months, but this had no significance or impact on long-term survival. None of the prognostic factors assessed had an impact on late survival, although no patients with more than three liver metastases survived beyond 40 months. Conclusions Although Carcinoembryonic antigen levels and number of metastases are prognostic factors that limit disease-free survival, they had no impact on 5-year survival and, therefore, should not determine exclusion from surgical treatment. Resection is the best treatment option for synchronous colorectal liver metastases, and even for patients with multiple metastases, large tumors and extrahepatic disease, it can provide long-term survival rates over 38%.

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Surgery and metastases of stomach cancer in liver

Medical alphabet ◽

10.33667/2078-5631-2020-29-21-24 ◽

2020 ◽

pp. 21-24

Author(s):

F. M. Dzhuraev ◽

S. L. Gutorov ◽

E. I. Borisova ◽

G. G. Khakimova

Keyword(s):

Gastric Cancer ◽

Liver Metastases ◽

Lymphovascular Invasion ◽

Peritoneal Dissemination ◽

Surgical Removal ◽

Relapse Free Survival ◽

Cancer Markers ◽

Free Survival ◽

The Poor ◽

Isolated Liver

Liver metastases of gastric cancer determine the poor prognosis. Until now The expediency of their surgical removal has been controversial. However, according to a number of studies, the removal of potentially operable isolated liver metastases allows a significant increase of overall and relapse-free survival in some cases. The review is dedicated to the analysis of prognostic factors that allow selecting patients for surgical removal of liver metastases of gastric cancer. The main criteria are: effective perioperative chemotherapy; stage under T4, N0, absence of lymphovascular invasion, absence of peritoneal dissemination, number less than 3, size up to 4 cm, localization of metastases in one lobe, low level of cancer markers CA 19-9 and CEA.

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YY1 Silencing Induces 5-Fluorouracil-Resistance and BCL2L15 Downregulation in Colorectal Cancer Cells: Diagnostic and Prognostic Relevance

International Journal of Molecular Sciences ◽

10.3390/ijms22168481 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8481

Author(s):

Silvia Vivarelli ◽

Luca Falzone ◽

Saverio Candido ◽

Benjamin Bonavida ◽

Massimo Libra

Keyword(s):

Colorectal Cancer ◽

Response To Therapy ◽

Advanced Stage ◽

Relapse Free Survival ◽

Free Survival ◽

Expression Levels ◽

Single Cell Sequencing ◽

Yin Yang 1 ◽

Anti Cancer ◽

Colorectal Cancer Cells

Colorectal cancer (CRC) is characterized by genetic heterogeneity and is often diagnosed at an advanced stage. Therefore, there is a need to identify novel predictive markers. Yin Yang 1 (YY1) is a transcription factor playing a dual role in cancer. The present study aimed to investigate whether YY1 expression levels influence CRC cell response to therapy and to identify the transcriptional targets involved. The diagnostic and prognostic values of YY1 and the identified factor(s) in CRC patients were also explored. Silencing of YY1 increased the resistance to 5-Fluorouracil-induced cytotoxicity in two out of four CRC cells with different genotypes. BCL2L15/Bfk pro-apoptotic factor was found selectively expressed in the responder CRC cells and downregulated upon YY1 knockdown. CRC dataset analyses corroborated a tumor-suppressive role for both YY1 and BCL2L15 whose expressions were inversely correlated with aggressiveness. CRC single-cell sequencing dataset analyses demonstrated higher co-expression levels of both YY1 and BCL2L15 within defined tumor cell clusters. Finally, elevated levels of YY1 and BCL2L15 in CRC patients were associated with larger relapse-free survival. Given their observed anti-cancer role, we propose YY1 and BCL2L15 as candidate diagnostic and prognostic CRC biomarkers.

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Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

Nature Communications ◽

10.1038/s41467-021-22450-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Takashi Nishina ◽

Yutaka Deguchi ◽

Daisuke Ohshima ◽

Wakami Takeda ◽

Masato Ohtsuka ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Cells ◽

Human Cancer ◽

Tumor Development ◽

Gene Signature ◽

Free Survival ◽

Expression Of Genes ◽

Reporter Mice ◽

Interleukin 11

AbstractInterleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

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Development of a genomic predictive model for cholangiocarcinoma using copy number alteration data

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-207346 ◽

2021 ◽

pp. jclinpath-2020-207346

Author(s):

Inês Tavares ◽

Ricardo Martins ◽

Ilda Patrícia Ribeiro ◽

Luísa Esteves ◽

Francisco Caramelo ◽

...

Keyword(s):

Survival Analysis ◽

Copy Number ◽

Patient Management ◽

Copy Number Alteration ◽

Comparative Genomic Hybridisation ◽

Support Vector ◽

Comparative Genomic ◽

Support Vector Machine Algorithm ◽

Rare Tumour ◽

Genomic Model

AimsCholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma.MethodsDNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed.ResultsWith these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3–22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC.ConclusionsThis genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.

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Evaluation of Histopathological Heterogeneity After Preoperative Chemotherapy in Patients With Liver Metastases from Colorectal Cancer

10.21203/rs.3.rs-192547/v1 ◽

2021 ◽

Author(s):

Nobuhisa matsuhashi ◽

Hiroyuki Tomita ◽

Takazumi Kato ◽

Yoshinori Iwata ◽

Satoshi Matsui ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Surgical Oncology ◽

Resected Specimen ◽

Histopathological Changes ◽

School Of Medicine ◽

Response To Chemotherapy ◽

Grade 3 ◽

The Right

Abstract Background: Patients with liver metastases from colorectal cancer (CRLMs) frequently receive chemotherapy prior to liver resection. Histopathological assessment of the resected specimen can evaluate the response to chemotherapy. This study analyzed the correlation between histopathological changes in the primary site and liver metastases. Patients and Methods: This study comprised 45 patients with resectable CRLMs at the Surgical Oncology Department of Gifu University School of Medicine from January 2006 to August 2015. Results: The study included 24 men and 21 women. The primary colonic tumor was located in the right side in 13 (28.9%) patients and the left side in 32 (71.9%) patients. We evaluated patients with metastatic colorectal cancer (31/45) after excluding those in whom histopathological heterogeneity between the primary and liver metastasis changed to grade 3 after chemotherapy. We compared the group which underwent hepatectomy after chemotherapy (n=25) with that underwent hepatectomy alone (n=6). In 16 (53.3%) out of 25 patients, histopathological heterogeneity of the liver metastasis was lost (p=0.04). Conclusion: Chemotherapy appears to change histopathological heterogeneity.Our study suggests that the change of intratumoral heterogeneity reflect by the response of chemotherapy.

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Higher titer hepatitis B core antibody predicts a higher risk of liver metastases and worse survival in patients with colorectal cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02369-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ziyao Li ◽

Shaofei Li ◽

Hangbo Tao ◽

Yixiang Zhan ◽

Kemin Ni ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Hepatitis B ◽

Liver Metastases ◽

Cancer Patients ◽

Hepatic Metastasis ◽

High Titer ◽

Poor Overall Survival ◽

Free Survival ◽

Colorectal Cancer Patients

Abstract Background There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients. Methods Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed. Results Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718–7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789–11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054–13.369; P = .041) in the anti-HBc positive cases. Conclusions Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.

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