Bio-inspired Model Classification of Squamous Cell Carcinoma in Cervical Cancer using SVM

Cervical cancer is traditionally classified into two major histological subtypes, cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CA). However, heterogeneity exists among patients, comprising possible subpopulations with distinct molecular profiles. We applied consensus clustering to 307 methylation samples with cervical cancer from The Cancer Genome Atlas (TCGA). Fisher’s exact test was used to perform transcription factors (TFs) and genomic region enrichment. Gene expression profiles were downloaded from TCGA to assess expression differences. Immune cell fraction was calculated to quantify the immune cells infiltration. Putative neo-epitopes were predicted from somatic mutations. Three subclasses were identified: Class 1 correlating with the CA subtype and Classes 2 and 3 dividing the CSCC subtype into two subclasses. We found the hypomethylated probes in Class 3 exhibited strong enrichment in promoter region as compared with Class 2. Five TFs significantly enriched in the hypomethylated promoters and their highly expressed target genes in Class 3 functionally involved in the immune pathway. Gene function analysis revealed that immune-related genes were significantly increased in Class 3, and a higher level of immune cell infiltration was estimated. High expression of 24 immune genes exhibited a better overall survival and correlated with neo-epitope burden. Additionally, we found only two immune-related driver genes, CARD11 and JAK3, to be significantly increased in Class 3. Our analyses provide a classification of the largest CSCC subtype into two new subclasses, revealing they harbored differences in immune-related gene expression.

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Faculty Opinions recommendation of Molecular classification of head and neck squamous cell carcinoma using cDNA microarrays.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007599.96155 ◽

2002 ◽

Author(s):

Alejandro Schaffer

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cdna Microarrays ◽

Molecular Classification ◽

Neck Squamous Cell Carcinoma

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Classification of lung adenocarcinoma and squamous cell carcinoma samples based on their gene expression profile in the sbv IMPROVER Diagnostic Signature Challenge

Systems Biomedicine ◽

10.4161/sysb.25983 ◽

2013 ◽

Vol 1 (4) ◽

pp. 268-277 ◽

Cited By ~ 7

Author(s):

Rotem Ben-Hamo ◽

Stephanie Boue ◽

Florian Martin ◽

Marja Talikka ◽

Sol Efroni

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Gene Expression Profile ◽

Expression Profile ◽

Squamous Cell ◽

Diagnostic Signature

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Molecular Classification of Oral Squamous Cell Carcinoma

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2016/19967.8565 ◽

2016 ◽

Cited By ~ 5

Author(s):

Radhika Manoj Bavle

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Classification

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Toward a Molecular Classification of the Head and Neck Squamous Cell Carcinoma

10.5772/intechopen.93982 ◽

2020 ◽

Author(s):

Amalia Raluca Ceausu ◽

Eugen Radu Boia ◽

Eugen Sorin Boia ◽

Anca Maria Cimpean ◽

Marius Raica

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Molecular Classification ◽

Neck Squamous Cell Carcinoma

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Association between polymorphisms in TP53 and XRCC1 genes and the high-risk HPV and tumor markers in women with cervical cancer

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2019.07.26-33 ◽

2019 ◽

pp. 26-33

Author(s):

Ж.Т. Исакова ◽

В.Н. Кипень ◽

Н.М. Букуев ◽

Э.Т. Талайбекова ◽

К.А. Айтбаев ◽

...

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Tumor Markers ◽

Squamous Cell ◽

Tp53 Gene ◽

Kyrgyz Republic ◽

Hpv 16 ◽

Pcr Rflp ◽

High Risk Hpv

Цель - оценить ассоциацию генов TР53 (rs1042522) и XRCC1 (rs25487, rs1799782) со статусом по вирусу папилломы человека (ВПЧ) и уровнем онкомаркеров у женщин киргизской национальности с раком шейки матки (РШМ). Материалы и методы. Исследование проведено по типу «случай-контроль» и включало 103 женщин с гистологически верифицированным диагнозом РШМ и 102 женщин без онкологической патологии в анамнезе. Генотипирование пациентов осуществлялось методом ПЦР-ПДРФ. Проведено типировование ВПЧ 16 и 18 типов, в сыворотке крови определены уровни ракового эмбрионального антигена (РЭА) и SCC (squamous cell carcinoma antigen). Результаты. Генотипы Pro/Pro и Arg/Pro полиморфизма p.Arg72Pro гена ТР53 были ассоциированы с наличием у женщин с РШМ ВПЧ 16 типа - ОШ=1,98 (95% ДИ=1,01-3,86, p=0,04), а генотип Pro/Pro полиморфизма p.Arg72Pro гена ТР53 - с ВПЧ 18 типа - ОШ=9,15 (95% ДИ=1,78-46,96, p=0,002). Высокие уровни онкомаркеров РЭА и SCC чаще встречаются у пациентов с РШМ, имеющих размер первичного опухолевого узла более 4 см. Патологически высокие уровни РЭА и SCC ассоциированы преимущественно с ВПЧ 16 типа. Заключение. Наличие аллеля Pro (генотипов Pro/Pro и Pro/Arg) по ОНП p.Arg72Pro (ген ТР53) у женщин с РШМ ассоциировано с положительным статусом по высокоонкогенным ВПЧ 16 и 18 типов. Aim: Evaluation of the role of TР53 (rs1042522), XRCC1 (rs25487, rs1799782) gene depending on the human papillomavirus (HPV), morphological parameters of the tumor and tumor markers of the blood among women with cervical cancer (CC) in Kyrgyz Republic. Methods. This was a case-control study of 205 women of Kyrgyz origin with morphologically verified CC (N=103) and 102 women without cancer and chronic diseases. Genotyping was performed by PCR-RFLP method. HPV 16 and 18 types, levels of squamous cell carcinoma (SCC) and сarcinoembryonic antigen (CEA) tumor markers were detected. Results. A relationship has been identified between the genetic and clinical and biochemical parameters: Pro/Pro и Arg/Pro for single-nucleotide polymorphism p.Arg72Pro of the ТР53 gene were associated with HPV 16 type - OR 1,98 (95% CI=[1,01-3,86]), p=0,04; Pro/Pro for p.Arg72Pro of the ТР53 - with HPV 18 type - OR =9,15 (95% CI=[1,78-46,96]), p=0,002. Among patients with tumor size of more than 4 cm are more common high levels of CEA and SCC tumor markers. High levels of CEA and SCC are associated mainly with type 16 HPV. Conclusions. The results of the present study suggest that the presence of the Pro allele (genotypes Pro/Pro and Pro/Arg) by SNP p.Arg72Pro (TP53 gene) among women with cervical cancer is associated with a positive status for highly oncogenic HPV 16 and 18 types.

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